Search results for: external risks

Authors: Omer Livvarcin, Mary Kay Park, Michael Miles

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The current literature includes a few studies that mention the impact of relations between teams, the business environment, and experiences from previous projects. There is, however, limited research that treats the phenomenon of project atmosphere (PA) as a whole. This is especially true of research identifying parameters and sub-parameters, which allow project management (PM) teams to build a project culture that ultimately imbues project success. This study’s findings identify a number of key project atmosphere parameters and sub-parameters that affect project management success. One key parameter identified in the study is a cluster related to cultural concurrence, including artifacts such as policies and mores, values, perceptions, and assumptions. A second cluster centers on motivational concurrence, including such elements as project goals and team-member expectations, moods, morale, motivation, and organizational support. A third parameter cluster relates to experiential concurrence, with a focus on project and organizational memory, previous internal PM experience, and external environmental PM history and experience). A final cluster of parameters is comprised of those falling in the area of relational concurrence, including inter/intragroup relationships, role conflicts, and trust. International and intercultural project management data was collected and analyzed from the following countries: Canada, China, Nigeria, South Korea and Turkey. The cross-cultural nature of the data set suggests increased confidence that the findings will be generalizable across cultures and thus applicable for future international project management success. The intent of the identification of project atmosphere as a critical project management element is that a clear understanding of the dynamics of its sub-parameters upon projects may significantly improve the odds of success of future international and intercultural projects.

Keywords: project management, project atmosphere, cultural concurrence, motivational concurrence, relational concurrence

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Authors: Riccardo Cacciotti, Jiri Frankl, Benjamin Wolf, Michael Machacek

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Moisture fluctuations govern the occurrence of fungi-related problems in buildings, which may impose significant health risks for users and even lead to structural failures. Several numerical engineering models attempt to capture the complexity of mold growth on building materials. From real life observations, in cases with suppressed daily variations of boundary conditions, e.g. in crawlspaces, mold growth model predictions well correspond with the observed mold growth. On the other hand, in cases with substantial diurnal variations of boundary conditions, e.g. in the ventilated cavity of a cold flat roof, mold growth predicted by the models is significantly overestimated. This study, founded by the Grant Agency of the Czech Republic (GAČR 20-12941S), aims at gaining a better understanding of mold growth behavior on solid wood, under varying boundary conditions. In particular, the experimental investigation focuses on the response of mold to changing conditions in the boundary layer and its influence on heat and moisture transfer across the surface. The main results include the design and construction at the facilities of ITAM (Prague, Czech Republic) of an innovative device allowing for the simulation of changing environmental conditions in buildings. It consists of a square section closed circuit with rough dimensions 200 × 180 cm and cross section roughly 30 × 30 cm. The circuit is thermally insulated and equipped with an electric fan to control air flow inside the tunnel, a heat and humidity exchange unit to control the internal RH and variations in temperature. Several measuring points, including an anemometer, temperature and humidity sensor, a loading cell in the test section for recording mass changes, are provided to monitor the variations of parameters during the experiments. The research is ongoing and it is expected to provide the final results of the experimental investigation at the end of 2022.

Keywords: moisture, mold growth, testing, wood

Procedia PDF Downloads 133

Authors: Sergejs Kolesovs, Pavels Semjonovs

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Whey and dairy wastewaters if disposed in the environment without proper treatment, cause serious environmental risks contributing to overall and particular environmental pollution and climate change. Biological treatment of wastewater is considered to be most eco-friendly approach, as compared to the chemical treatment methods. Research shows, that dairy wastewater can potentially be remediated by use of microalgae thussignificantly reducing the content of carbohydrates, P, N, K and other pollutants. Moreover, it has been shown, that use of dairy wastewaters results in higher microalgae biomass production. In recent decades microalgal biomass has entailed a big interest for its potential applications in pharmaceuticals, biomedicine, health supplementation, cosmetics, animal feed, plant protection, bioremediation and biofuels. It was shown, that lipids productivity on whey and dairy wastewater is higher as compared with standard cultivation media and occurred without the necessity of inducing specific stress conditions such as N starvation. Moreover, microalgae biomass production as usually associated with high production costs may benefit from perspective of both reasons – enhanced microalgae biomass or target substances productivity on cheap growth substrate and effective management of whey and dairy wastewaters, which issignificant for decrease of total production costs in both processes. Obviously, it became especially important when large volume and low cost industrial microalgal biomass production is anticipated for further use in agriculture of crops as plant growth stimulants, biopesticides soil fertilisers or remediating solutions. Environmental load of dairy wastewaters can be significantly decreased when microalgae are grown in coculture with other microorganisms. This enhances the utilisation of lactose, which is main C source in whey and dairy wastewaters when it is not metabolised easily by most microalgal species chosen. Our study showsthat certain microalgae strains can be used in treatment of residual sugars containing industrial wastewaters and decrease of their concentration thus approving that further extensive research on dairy wastewaters pre-treatment optionsfor effective cultivation of microalgae, carbon uptake and metabolism, strain selection and choice of coculture candidates is needed for further optimisation of the process.

Keywords: microalgae, whey, dairy wastewaters, sustainability, plant biostimulants

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Authors: Akinnubi Rufus Temidayo

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Coastal West Africa is highly sensitive to climate variability, driven by complex ocean-atmosphere interactions that shape temperature, precipitation, and extreme weather. Radiative feedback mechanisms—such as water vapor feedback, cloud-radiation interactions, and surface albedo—play a critical role in modulating these patterns. Yet, limited research addresses these feedbacks in climate models specific to West Africa’s coastal zones, creating challenges for accurate climate projections and adaptive planning. This study aims to evaluate the influence of radiative feedbacks on the coastal climate of West Africa by quantifying the effects of water vapor, cloud cover, and sea surface temperature (SST) on the region’s radiative balance. The study uses a regional climate model (RCM) to simulate feedbacks over a 20-year period (2005-2025) with high-resolution data from CORDEX and satellite observations. Key mechanisms investigated include (1) Water Vapor Feedback—the amplifying effect of humidity on warming, (2) Cloud-Radiation Interactions—the impact of cloud cover on radiation balance, especially during the West African Monsoon, and (3) Surface Albedo and Land-Use Changes—effects of urbanization and vegetation on the radiation budget. Preliminary results indicate that radiative feedbacks strongly influence seasonal climate variability in coastal West Africa. Water vapor feedback amplifies dry-season warming, cloud-radiation interactions moderate surface temperatures during monsoon seasons, and SST variations in the Atlantic affect the frequency and intensity of extreme rainfall events. The findings suggest that incorporating these feedbacks into climate planning can strengthen resilience to climate impacts in West African coastal communities. Further research should refine regional models to capture anthropogenic influences like greenhouse gas emissions, guiding sustainable urban and resource planning to mitigate climate risks.

Keywords: west africa, radiative, climate, resilence, anthropogenic

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Authors: A. Akbarpour, M. R. Adib Ramezani, M. Zhian, N. Ghorbani Amirabad

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One way to improve the performance of structures against of earthquake is passive control which requires no external power source. In this research, tuned liquid column dampers which are among of systems with the capability to transfer energy between various modes of vibration, are used. For the first time, a liquid column damper for vibration control structure is presented. After modeling this structure in design building software and performing the static and dynamic analysis and obtaining the necessary parameters for the design of tuned liquid column damper, the whole structure will be analyzed in finite elements software. The tuned liquid column dampers are installed on the structure and nonlinear time-history analysis is done in two cases of structures; with and without dampers. Finally the seismic behavior of building in the two cases will be examined. In this study the nonlinear time-history analysis on a twelve-story steel structure equipped with damper subject to records of earthquake including Loma Prieta, Northridge, Imperiall Valley, Pertrolia and Landers was performed. The results of comparing between two cases show that these dampers have reduced lateral displacement and acceleration of levels on average of 10%. Roof displacement and acceleration also reduced respectively 5% and 12%. Due to structural asymmetric in the plan, the maximum displacements of surrounding structures as well as twisting were studied. The results show that the dampers lead to a 10% reduction in the maximum response of structure stories surrounding points. At the same time, placing the dampers, caused to reduce twisting on the floor plan of the structure, Base shear of structure in the different earthquakes also has been reduced on the average of 6%.

Keywords: retrofitting, passive control, tuned liquid column damper, finite element analysis

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Authors: Kevin Soubly, Kaysara Khatun

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This study applies the existing Middle-Out Perspective (MOP) as a complementing analytical alternative to the customary dichotomous options of top-down vs. bottom-up strategies of international development and commons governance. It expands the framework by applying it to a new context of land management and environmental change, enabling fresh understandings of decision making around land use. Using a case study approach in Central Kalimantan, Indonesia among a village of indigenous Dayak, this study explores influences from both internal and external middle actors, utilizing qualitative empirical evidence and incorporating responses across 25 village households and 11 key stakeholders. Applying the factors of 'agency' and 'capacity' specific to the MOP, this study demonstrates middle actors’ unique capabilities and criticality to change due to their influence across various levels of decision-making. Study results indicate that middle actors play a large role, both passively and actively, both directly and indirectly, across various levels of decision-making, perception-shaping, and commons governance. In addition, the prominence of novel 'passive' middle actors, such as the internet, can provide communities themselves with a level of agency beyond that provided by other middle actors such as NGOs and palm oil industry entities – which often operate at the behest of the 'top' or out of self-interest. Further, the study posits that existing development and decision-making frameworks may misidentify the 'bottom' as the 'middle,' raising questions about traditional development and livelihood discourse, strategies, and support, from agricultural production to forest management. In conclusion, this study provides recommendations including that current policy preconceptions be reevaluated to engage middle actors in locally-adapted, integrative manners in order to improve governance and rural development efforts more broadly.

Keywords: environmental management, governance, Indonesia, land use, middle actors, middle-out perspective

Procedia PDF Downloads 115

Authors: Mohamed Khiatine, Amal Medjnoun, Ramdane Bahar

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The North Algeria is a highly seismic zone, as evidenced by the historical seismicity. During the past two decades, it has experienced several moderate to strong earthquakes. Therefore, the geotechnical engineering problems that involve dynamic loading of soils and soil-structure interaction system requires, in the presence of saturated loose sand formations, liquefaction studies. Bejaia city, located in North-East of Algiers, Algeria, is a part of the alluvial plain which covers an area of approximately 750 hectares. According to the Algerian seismic code, it is classified as moderate seismicity zone. This area had not experienced in the past urban development because of the different hazards identified by hydraulic and geotechnical studies conducted in the region. The low bearing capacity of the soil, its high compressibility and the risk of liquefaction and flooding are among these risks and are a constraint on urbanization. In this area, several cases of structures founded on shallow foundations have suffered damages. Hence, the soils need treatment to reduce the risk. Many field and laboratory investigations, core drilling, pressuremeter test, standard penetration test (SPT), cone penetrometer test (CPT) and geophysical down hole test, were performed in different locations of the area. The major part of the area consists of silty fine sand , sometimes heterogeneous, has not yet reached a sufficient degree of consolidation. The ground water depth changes between 1.5 and 4 m. These investigations show that the liquefaction phenomenon is one of the critical problems for geotechnical engineers and one of the obstacles found in design phase of projects. This paper presents an analysis to evaluate the liquefaction potential, using the empirical methods based on Standard Penetration Test (SPT), Cone Penetration Test (CPT) and shear wave velocity and numerical analysis. These liquefaction assessment procedures indicate that liquefaction can occur to considerable depths in silty sand of harbor zone of Bejaia.

Keywords: earthquake, modeling, liquefaction potential, laboratory investigations

Procedia PDF Downloads 353

Authors: Frederico Fialho Teixeira, Islam Mashaly, Maryam Shafiei, Jurij Karlovsek

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The ubiquity of data gathering and smart technologies, advancements in virtual technologies, and the development of the internet of things (IoT) have created urgent demands for the development of frameworks and efficient workflows for data collection, visualisation, and analysis. Digital twin, in different scales of the city into the building, allows for bringing together data from different sources to generate fundamental and illuminating insights for the management of current facilities and the lifecycle of amenities as well as improvement of the performance of current and future designs. Over the past two decades, there has been growing interest in the topic of digital twin and their applications in city and building scales. Most such studies look at the urban environment through a homogeneous or generalist lens and lack specificity in particular characteristics or identities, which define an urban university campus. Bridging this knowledge gap, this paper offers a framework for developing a digital twin for a university campus that, with some modifications, could provide insights for any large-scale digital twin settings like towns and cities. It showcases how currently unused data could be purposefully combined, interpolated and visualised for producing analysis-ready data (such as flood or energy simulations or functional and occupancy maps), highlighting the potential applications of such a framework for campus planning and policymaking. The research integrates campus-level data layers into one spatial information repository and casts light on critical data clusters for the digital twin at the campus level. The paper also seeks to raise insightful and directive questions on how digital twin for campus can be extrapolated to city-scale digital twin. The outcomes of the paper, thus, inform future projects for the development of large-scale digital twin as well as urban and architectural researchers on potential applications of digital twin in future design, management, and sustainable planning, to predict problems, calculate risks, decrease management costs, and improve performance.

Keywords: digital twin, smart campus, framework, data collection, point cloud

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Authors: Liu Canqi, Zeng Junsheng

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This study identifies two typical bottlenecks that occur when a vehicle cannot change lanes: car following and car stopping. The ideas of traffic field and traffic mass are presented in this work. When there are other vehicles in front of the target vehicle within a particular distance, a force is created that affects the target vehicle's driving speed. The characteristics of the driver and the vehicle collectively determine the traffic mass; the driving speed of the vehicle and external variables have no bearing on this. From a physical level, this study examines the vehicle's bottleneck when following a car, identifies the outside factors that have an impact on how it drives, takes into account that the vehicle will transform kinetic energy into potential energy during deceleration, and builds a calculation model for traffic mass. The energy-time conversion coefficient is created from an economic standpoint utilizing the social average wage level and the average cost of motor fuel. Vissim simulation program measures the vehicle's deceleration distance and delays under the Wiedemann car-following model. The difference between the measured value of deceleration delay acquired by simulation and the theoretical value calculated by the model is compared using the conversion calculation model of traffic mass and deceleration delay. The experimental data demonstrate that the model is reliable since the error rate between the theoretical calculation value of the deceleration delay obtained by the model and the measured value of simulation results is less than 10%. The article's conclusion is that the traffic field has an impact on moving cars on the road and that physical and socioeconomic factors should be taken into account while studying vehicle-following behavior. The deceleration delay value of a vehicle's driving and traffic mass have a socioeconomic relationship that can be utilized to calculate the energy-time conversion coefficient when dealing with the bottleneck of cars stopping and starting.

Keywords: traffic field, social economics, traffic mass, bottleneck, deceleration delay

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Authors: Nuria Rubio, María Campo, Joana Ruiz, Paola Vecino

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Renewable energies have been proposed for some years as a solution to the ecological crisis caused by traditional fuels. The installation of solar parks for electricity production is therefore necessary for a transition to cleaner energy. Additionally, spaces occupied by solar parks can be ideal places for biodiversity promotion consisting in controlled areas allowing free transit of numerous animal species in absence of phytosanitary products or other substances commonly used in rural areas. The main objective of this project is increasing local biodiversity. Secondary objectives include the installation of beehives with Apis mellifera iberiensis swarms (native honeybee species), the monitoring and periodic evaluation of the state of health and demographic progression of these swarms and study of biodiversity increase in these areas, mainly due to the presence of Apis mellifera iberiensis. Prior to bee-hives installation, a preliminary study of the area is carried out to quantify floral load, biocenosis and geo-climatological characteristics of the area of study for determining the optimal number of hives for the benefit of the local ecosystem. Once beehives set up, the bee-swarms health status is monitored and evaluated quarterly using monitoring systems. Parameters studies are weight, humidity inside the hive, external and internal temperature, and sound inside the hive. Furthermore, a biodiversity study of the area was conducted by direct observation and quantification of species (S) in the area of bee-foraging (1 km around the beehives). A great diversity of species has been detected in the area of study. Therefore, the population of Apis mellifera iberiensis is not displacing other pollinators in the area, on the contrary, results show that it is contributing to the pollination of the different plant species enhancing wild bees’ biodiversity.

Keywords: biodiversity, honeybee, pollination, solar park

Procedia PDF Downloads 54

Authors: Odunayo S. Faluse, Roger Telfer

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Customer relationship management is a business strategy that is centred on the idea that ‘Customer is the driving force of any business’ i.e. Customer is placed in a central position in any business. However, this belief coupled with the advancement in information technology in the past twenty years has experienced a change. In any form of business today it can be concluded that customers are the modern dictators to whom the industry always adjusts its business operations due to the increase in availability of information, intense market competition and ever growing negotiating ideas of customers in the process of buying and selling. The most vital role of any organization is to satisfy or meet customer’s needs and demands, which eventually determines customer’s long-term value to the industry. Therefore, this paper analyses and describes the application of customer relationship management operational strategies in some of the major industries in business. Both developed and up-coming companies nowadays value the quality of customer services and client’s loyalty, they also recognize the customers that are not very sensitive when it comes to changes in price and thereby realize that attracting new customers is more tasking and expensive than retaining the existing customers. However, research shows that several factors have recently amounts to the sudden rise in the execution of CRM strategies in the marketplace, such as a diverted attention of some organization towards integrating ideas in retaining existing customers rather than attracting new one, gathering data about customers through the use of internal database system and acquiring of external syndicate data, also exponential increase in technological intelligence. Apparently, with this development in business operations, CRM research in Academia remain nascent; hence this paper gives detailed critical analysis of the recent advancement in the use of CRM and key research opportunities for future development in using the implementation of CRM as a determinant factor for successful business optimization.

Keywords: agriculture, banking, business strategies, CRM, education, healthcare

Procedia PDF Downloads 223

Authors: Antonio Pizzarello, Oris Friesen

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Networks, such as the electric power grid, must demonstrate exemplary performance and integrity. Integrity depends on the quality of both the system design model and the deployed software. Integrity of the deployed software is key, for both the original versions and the many that occur throughout numerous maintenance activity. Current software engineering technology and practice do not produce adequate integrity. Distributed systems utilize networks where each node is an independent computer system. The connections between them is realized via a network that is normally redundantly connected to guarantee the presence of a path between two nodes in the case of failure of some branch. Furthermore, at each node, there is software which may fail. Self-stabilizing protocols are usually present that recognize failure in the network and perform a repair action that will bring the node back to a correct state. These protocols first introduced by E. W. Dijkstra are currently present in almost all Ethernets. Super stabilization protocols capable of reacting to a change in the network topology due to the removal or addition of a branch in the network are less common but are theoretically defined and available. This paper describes how to use the Software Integrity Assessment (SIA) methodology to analyze self-stabilizing software. SIA is based on the UNITY formalism for parallel and distributed programming, which allows the analysis of code for verifying the progress property p leads-to q that describes the progress of all computations starting in a state satisfying p to a state satisfying q via the execution of one or more system modules. As opposed to demonstrably inadequate test and evaluation methods SIA allows the analysis and verification of any network self-stabilizing software as well as any other software that is designed to recover from failure without external intervention of maintenance personnel. The model to be analyzed is obtained by automatic translation of the system code to a transition system that is based on the use of the weakest precondition.

Keywords: network, power grid, self-stabilization, software integrity assessment, UNITY, weakest precondition

Procedia PDF Downloads 223

Authors: Abdorrasoul Malekpour, Mohammad Ghorbani Mojtaba Mortazavi, Mohammadreza Fattahi, Mohammad Hassan Meshkibaf, Ali Fakhrzad, Saeid Salehi, Saeideh Zahedi, Amir Ahmadimoghaddam, Parviz Farzadnia Dr., Mohammadreza Hajyani Asl Bs

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Hepatitis B as an infectious disease has eight main genotypes (A–H). The aim of this study is to Bioinformatically identify Rare Codon Clusters (RCC) in proteins structure of HBV. For detection of protein family accession numbers (Pfam) of HBV proteins; used of uni-prot database and Pfam search tool were used. Obtained Pfam IDs were analyzed in Sherlocc program and RCCs in HBV proteins were detected. In further, the structures of TrEMBL entries proteins studied in PDB database and 3D structures of the HBV proteins and locations of RCCs were visualized and studied using Swiss PDB Viewer software. Pfam search tool have found nine significant hits and 0 insignificant hits in 3 frames. Results of Pfams studied in the Sherlocc program show this program not identified RCCs in the external core antigen (PF08290) and truncated HBeAg protein (PF08290). By contrast the RCCs become identified in Hepatitis core antigen (PF00906) Large envelope protein S (PF00695), X protein (PF00739), DNA polymerase (viral) N-terminal domain (PF00242) and Protein P (Pf00336). In HBV genome, seven RCC identified that found in hepatitis core antigen, large envelope protein S and DNA polymerase proteins and proteins structures of TrEMBL entries sequences that reported in Sherlocc program outputs are not complete. Based on situation of RCC in structure of HBV proteins, it suggested those RCCs are important in HBV life cycle. We hoped that this study provide a new and deep perspective in protein research and drug design for treatment of HBV.

Keywords: rare codon clusters, hepatitis B virus, bioinformatic study, infectious disease

Procedia PDF Downloads 488

Authors: N.Quaranta, M. Caligaris, R. Varoli, A. Cristobal, M. Unsen, H. López

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Corncobs are agricultural wastes and they can be used as fuel or as raw material in different industrial processes like cement manufacture, contaminant adsorption, chemical compound synthesis, etc. The aim of this work is to characterize this waste and analyze the feasibility of its use as a pore-forming material in the manufacture of lightweight ceramics for the civil construction industry. The characterization of raw materials is carried out by using various techniques: electron diffraction analysis X-ray, differential and gravimetric thermal analyses, FTIR spectroscopy, ecotoxicity evaluation, among others. The ground corncobs, particle size less than 2 mm, are mixed with clay up to 30% in volume and shaped by uniaxial pressure of 25 MPa, with 6% humidity, in moulds of 70mm x 40mm x 18mm. Then the green bodies are heat treated at 950°C for two hours following the treatment curves used in ceramic industry. The ceramic probes are characterized by several techniques: density, porosity and water absorption, permanent volumetric variation, loss on ignition, microscopies analysis, and mechanical properties. DTA-TGA analysis of corncobs shows in the range 20°-250°C a small loss in TGA curve and exothermic peaks at 250°-500°C. FTIR spectrum of the corncobs sample shows the characteristic pattern of this kind of organic matter with stretching vibration bands of adsorbed water, methyl groups, C–O and C–C bonds, and the complex form of the cellulose and hemicellulose glycosidic bonds. The obtained ceramic bodies present external good characteristics without loose edges and adequate properties for the market requirements. The porosity values of the sintered pieces are higher than those of the reference sample without waste addition. The results generally indicate that it is possible to use corncobs as porosity former in ceramic bodies without modifying the usual sintering temperatures employed in the industry.

Keywords: ceramic industry, biomass, recycling, hemicellulose glycosidic bonds

Procedia PDF Downloads 405

Authors: Mustapha Ouardouz, Mina Amharref, Abdessamed Bernoussi

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The future energy, for limited energy resources countries, goes through renewable energies (solar, wind etc.). The renewable energies constitute a major component of the energy strategy to cover a substantial part of the growing needs and contribute to environmental protection by replacing fossil fuels. Indeed, sustainable development involves the promotion of renewable energy and the preservation of the environment by the use of clean energy technologies to limit emissions of greenhouse gases and reducing the pressure exerted on the forest cover. So the impact studies, of the energy use on the environment and farm-related risks are necessary. For that, a global approach integrating all the various sectors involved in such project seems to be the best approach. In this paper we present an approach based on the multi criteria analysis and the realization of one pilot to achieve the development of an innovative geo-intelligent environmental platform. An implementation of this platform will collect, process, analyze and manage environmental data in connection with the nature of used energy in the studied region. As an application we consider a region in the north of Morocco characterized by intense agricultural and industrials activities and using diverse renewable energy. The strategic goals of this platform are; the decision support for better governance, improving the responsiveness of public and private companies connected by providing them in real time with reliable data, modeling and simulation possibilities of energy scenarios, the identification of socio-technical solutions to introduce renewable energies and estimate technical and implantable potential by socio-economic analyzes and the assessment of infrastructure for the region and the communities, the preservation and enhancement of natural resources for better citizenship governance through democratization of access to environmental information, the tool will also perform simulations integrating environmental impacts of natural disasters, particularly those linked to climate change. Indeed extreme cases such as floods, droughts and storms will be no longer rare and therefore should be integrated into such projects.

Keywords: renewable energies, decision aided tool, environment, simulation

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Authors: E. Bartkiene, V. Krungleviciute, J. Kucinskiene, R. Antanaitis, A. Kucinskas

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In calves less than 10-day-old, infection commonly cause severe diarrhoea and high mortality. To prevention of calves diseases a common practice is to treat calves with prophylactic antibiotics, in this case the use of lactic acid bacteria (LAB) is promising. Often LAB strains are incubated in comercial de Man-Rogosa-Sharpe (MRS) medium, the culture are centrifuged, the cells are washing with sterile water, and this suspension is used as a starter culture for animal health care. Juice of potatoe tubers is industrial wastes, wich may constitute a source of digestible nutrients for microorganisms. In our study the ability of LAB to utilize potatoe tubers juice in cell synthesis without external nutrient supplement was investigated, and the influence of multiplied LAB on calves blood parameters was evaluated. Calves were selected based on the analogy principle (treatment group (n=6), control group (n=8)). For the treatment group 14 days was given a 50 ml of fermented potatoe tubers juice containing 9.6 log10 cfu/ml of LAB. Blood parameters (gas and biochemical) were assessed by use of an auto-analyzers (Hitachi 705 and EPOC). Before the experiment, blood pH of treatment group calves was 7.33, control – 7.36, whereas, after 14 days, 7.28 and 7.36, respectively. Calves blood pH in the treatment group remained stable over the all experiment period. Concentration of PCO2 in control calves group blood increased from 63.95 to 70.93, whereas, in the treatment group decreased from 63.08 to 60.71. Concentration of lactate in the treatment group decreased from 3.20 mmol/l to 2.64 mmol/l, whereas, in control - increased from 3.95 mmol/l to 4.29 mmol/l. Concentration of AST in the control calves group increased from 50.18 IU/L to 58.9 IU/L, whereas, in treatment group decreased from 49.82 IU/L to 33.1 IU/L. We conclude that the 50 ml of fermented potatoe tubers juice containing 9.6 log10 cfu/ml of LAB per day, by using 14 days, reduced risk of developing acidosis (stabilizes blood pH (p < 0.05)), reduces lactates and PCO2 concentration (p < 0.05) and risk of liver lesions (reduces AST concentration (p < 0.005)) in blood of calves.

Keywords: alternative substrate, blood parameters, calves, lactic acid bacteria

Procedia PDF Downloads 313

Authors: Sopit Tubtimhin, Chaliya Wamaloon, Anchalee Supattagorn

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Background and Significance: Breast cancer is the most frequently diagnosed and leading cause of cancer death among women. This study aims to determine factors potentially predicting recurrence and long-term survival after the first recurrence in surgically treated patients between postmenopausal and younger women. Methods and Analysis: A retrospective cohort study was performed on 498 Thai women with invasive breast cancer, who had undergone mastectomy and been followed-up at Ubon Ratchathani Cancer Hospital, Thailand. We collected based on a systematic chart audit from medical records and pathology reports between January 1, 2002, and December 31, 2011. The last follow-up time point for surviving patients was December 31, 2016. A Cox regression model was used to calculate hazard ratios of recurrence and death. Findings: The median age was 49 (SD ± 9.66) at the time of diagnosis, 47% was post-menopausal women ( ≥ 51years and not experienced any menstrual flow for a minimum of 12 months), and 53 % was younger women ( ˂ 51 years and have menstrual period). Median time from the diagnosis to the last follow-up or death was 10.81 [95% CI = 9.53-12.07] years in younger cases and 8.20 [95% CI = 6.57-9.82] years in postmenopausal cases. The recurrence-free survival (RFS) for younger estimates at 1, 5 and 10 years of 95.0 %, 64.0% and 58.93% respectively, appeared slightly better than the 92.7%, 58.1% and 53.1% for postmenopausal women [HRadj = 1.25, 95% CI = 0.95-1.64]. Regarding overall survival (OS) for younger at 1, 5 and 10 years were 97.7%, 72.7 % and 52.7% respectively, for postmenopausal patients, OS at 1, 5 and 10 years were 95.7%, 70.0% and 44.5 respectively, there were no significant differences in survival [HRadj = 1.23, 95% CI = 0.94 -1.64]. Multivariate analysis identified five risk factors for negatively impacting on survival were triple negative [HR= 2.76, 95% CI = 1.47-5.19], Her2-enriched [HR = 2.59, 95% CI = 1.37-4.91], luminal B [HR = 2.29, 95 % CI=1.35-3.89], not free margin [HR = 1.98, 95%CI=1.00-3.96] and patients who received only adjuvant chemotherapy [HR= 3.75, 95% CI = 2.00-7.04]. Statistically significant risks of overall cancer recurrence were Her2-enriched [HR = 5.20, 95% CI = 2.75-9.80], triple negative [HR = 3.87, 95% CI = 1.98-7.59], luminal B [HR= 2.59, 95% CI = 1.48-4.54,] and patients who received only adjuvant chemotherapy [HR= 2.59, 95% CI = 1.48-5.66]. Discussion and Implications: Outcomes from this studies have shown that postmenopausal women have been associated with increased risk of recurrence and mortality. As the results, it provides useful information for planning the screening and treatment of early-stage breast cancer in the future.

Keywords: breast cancer, menopause status, recurrence-free survival, overall survival

Procedia PDF Downloads 163

Authors: Odaleia de O. Farias, Suzelene C. Marinho, Ecleidson B. Fragoso, Daniel S. Lima, Francisco R. S. Lira, Lara S. Araújo, Gabriel dos S. D. Soares

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In populous cities, prehospital care services that use vehicles alternative to ambulances are needed in order to reduce costs and improve response time to occurrences in areas with large concentration of people, such as leisure and tourism spaces. In this context, it was implanted a program called BIKE VIDA, that is innovative quick access and assistance program. The aim of this study is to describe the implantation and initial profile of occurrences performed by an urgency/emergency pre-hospital care service through paramedics on bicycles. It is a cross-sectional, descriptive study carried out in the city of Fortaleza, Ceara, Brazil. The data included service records from July to August 2017. Ethical aspects were respected. The service covers a perimeter of 4.5 km, divided into three areas with perimeter of 1.5 km for each paramedic, attending from 5 am to 9 pm. Materials transported by bicycles include External Automated Defibrillator - DEA, portable oxygen, oximeter, cervical collar, stethoscope, sphygmomanometer, dressing and immobilization materials and personal protective equipment. Occurrences are requested directly by calling the emergency number 192 or through direct approach to the professional. In the first month of the program, there were 93 emergencies/urgencies, mainly in the daytime period (71,0%), in males (59,7%), in the age range of 26 to 45 years (46,2%). The main nature was traumatic incidents (53.3%). Most of the cases (88,2%) did not require ambulance transport to the hospital, and there were two deaths. Pre-hospital service through bicycles is an innovative strategy in Brazil and has shown to be promising in terms of reducing costs and improving the quality of the services offered.

Keywords: emergency, response time, prehospital care, urgency

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Authors: Buhari Samaila, Sabiu Abdullahi, Buhari Maidamma

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Background: Contrast-enhanced computed tomography (CE-CT) is a technique that uses contrast media to improve image quality and diagnostic accuracy. It is a widely used imaging modality in medical diagnostics, offering high-resolution images for accurate diagnosis. However, concerns regarding the potential adverse effects of contrast media and radiation dose exposure have prompted ongoing investigation and assessment. It is important to assess the effects of contrast media and radiation dose in CE-CT procedures. Objective: This study aims to assess the effects of contrast media and radiation dose in contrast-enhanced computed tomography (CECT) procedures. Methods: A comprehensive review of the literature was conducted to identify studies related to contrast media effects and radiation dose assessment in CECT. Relevant data, including location, type of research, objective, method, findings, conclusion, authors, and year of publications, were extracted, analyzed, and reported. Results: The findings revealed that several studies have investigated the impacts of contrast media and radiation doses in CECT procedures, with iodinated contrast agents being the most commonly employed. Adverse effects associated with contrast media administration were reported, including allergic reactions, nephrotoxicity, and thyroid dysfunction, albeit at relatively low incidence rates. Additionally, radiation dose levels varied depending on the imaging protocol and anatomical region scanned. Efforts to minimize radiation exposure through optimization techniques were evident across studies. Conclusion: Contrast-enhanced computed tomography (CECT) remains an invaluable tool in medical imaging; however, careful consideration of contrast media effects and radiation dose exposure is imperative. Healthcare practitioners should weigh the diagnostic benefits against potential risks, employing strategies to mitigate adverse effects and optimize radiation dose levels for patient safety and effective diagnosis. Further research is warranted to enhance the understanding and management of contrast media effects and radiation dose optimization in CECT procedures.

Keywords: CT, contrast media, radiation dose, effect of radiation

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Authors: Babak Nemat

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Background and Purpose: Non-alcoholic fatty liver is one of the most common liver disorders, which, as the most important cause of death from liver disease, has unpleasant consequences and complications. The aim of this study was to investigate the effect of an educational intervention based on a health belief model to prevent non-alcoholic fatty liver among women. Materials and Methods: This experimental study was performed among 110 women referring to comprehensive health service centers in Malayer City, west of Iran, in 2023. Using the available sampling method, 110 participants were divided into experimental and control groups. The data collection tool included demographic characteristics and a questionnaire based on the health belief model. In the experimental group, three one-hour training sessions were conducted in the form of pamphlets, lectures, and group discussions. Data were analyzed using SPSS software version 21, by correlation tests, paired t-tests, and independent t-tests. Results: The mean age of participants was 38.07±6.28 years, and most of the participants were middle-aged, married, housewives with academic education, middle-income, and overweight. After the educational intervention, the mean scores of the constructs include perceived sensitivity (p=0.01), perceived severity (p=0.01), perceived benefits (p=0.01), guidance for internal (p=0.01), and external action (p=0.01), and perceived self-efficacy (p=0.01) in the experimental group were significantly higher than the control group. The score of perceived barriers in the experimental group decreased after training. The perceived obstacles score in the test group decreased after the training (15.2 ± 3.9 v.s 11.2 ± 3.3, (p<0.01). Conclusion: The findings of the study showed that the design and implementation of educational programs based on the constructs of the health belief model can be effective in preventing women from developing higher levels of non-alcoholic fatty liver.

Keywords: non-alcoholic fatty liver, health belief model, education, women

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Authors: Mohammad Mosaddik Rahman

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This study embarks on an exploratory journey to assess the pervasive issue of heavy metal contamination in the water bodies along Chittagong Coast, Bangladesh. Situated along the mesmerizing Bay of Bengal, known for its potential as an emerging tourist haven, economic zone, ship breaking yard, confronts significant environmental hurdles. The core of these challenges lies in the contamination from heavy metals such as lead, cadmium, chromium, and mercury, which detrimentally impact both the ecological integrity and public health of the region. This contamination primarily stems from industrial activities, particularly those involving metallurgical and chemical processes, which release these metals into the environment, leading to their accumulation in soil and water bodies. The study's primary aim is to conduct a thorough assessment of heavy metal pollution levels, alongside an analysis of nutrient variations, focusing on nitrates and nitrites. Methodologically, the study leverages systematic sampling and advanced analytical tools like the Hach 3900 spectrophotometer to ensure precise and reliable data collection. The implications of heavy metal presence are multifaceted, affecting microbial and aquatic life, and posing severe health risks to the local population, including respiratory problems, neurological disorders, and an increased risk of cancer. The results of this study highlight the urgent need for effective mitigation strategies and regulatory measures to address this critical issue. By providing a comprehensive understanding of the environmental and public health implications of heavy metal contamination in Chittagong Coast, this research endeavours to serve as a catalyst for change, emphasising the need for pollution control and advancements in water management policies. It is envisioned that the outcomes of this study will guide stakeholders in collaborating to develop and implement sustainable solutions, ultimately safeguarding the region’s environment and public health.

Keywords: heavy metal, environmental health, pollution control policies, shipbreaking yard

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Authors: P. Michael Preetam Raj, Souri Banerjee, Souvik Kundu

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Oxide based memristors were fabricated in order to establish its potential applications in analog/digital electronics. BaTiO₃-BiFeO₃ (BT-BFO) was employed as an active material, whereas platinum (Pt) and Nb-doped SrTiO₃ (Nb:STO) were served as a top and bottom electrodes, respectively. Piezoelectric force microscopy (PFM) was utilized to present the ferroelectricity and repeatable polarization inversion in the BT-BFO, demonstrating its effectiveness for resistive switching. The fabricated memristors exhibited excellent electrical characteristics, such as hysteresis current-voltage (I-V), high on/off ratio, high retention time, cyclic endurance, and low operating voltages. The band-alignment between the active material BT-BFO and the substrate Nb:STO was experimentally investigated using X-Ray photoelectron spectroscopy, and it attributed to staggered heterojunction alignment. An energy band diagram was proposed in order to understand the electrical transport in BT-BFO/Nb:STO heterojunction. It was identified that the I-V curves of these memristors have several discontinuities. Curve fitting technique was utilized to analyse the I-V characteristic, and the obtained I-V equations were found to be parabolic. Utilizing this analysis, a non-linear BT-BFO memristors equivalent circuit model was developed. Interestingly, the obtained equivalent circuit of the BT-BFO memristors mimics the identical electrical performance, those obtained in the fabricated devices. Based on the developed equivalent circuit, a finite state machine (FSM) design was proposed. Efforts were devoted to fabricate the same FSM, and the results were well matched with those in the simulated FSM devices. Its multilevel noise filtering and immunity to external noise characteristics were also studied. Further, the feature of variable negative resistance was established by controlling the current through the memristor.

Keywords: band alignment, finite state machine, polarization inversion, resistive switching

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Authors: Chetan Gupta, Ramesh Gupta

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Unmanned aerial vehicles, of all sizes, are prime targets of the wing morphing concept as their lightweight structures demand high aerodynamic stability while traversing unsteady atmospheric conditions. In this research study, a hybrid morphing technology is developed to aid the trailing edge of the aircraft wing to alter its camber as a monolithic element rather than functioning as conventional appendages like flaps. Kinematic tailoring, actuation techniques involving shape memory alloys (SMA), piezoelectrics – individually fall short of providing a simplistic solution to the conundrum of morphing aircraft wings. On the other hand, the feature of negligible hysteresis while actuating using compliant mechanisms has shown higher levels of applicability and deliverability in morphing wings of even large aircrafts. This research paper delves into designing a wing section model with a periodic, multi-stable compliant structure requiring lower orders of topological optimization. The design is sub-divided into three smaller domains with external hyperelastic connections to achieve deflections ranging from -15° to +15° at the trailing edge of the wing. To facilitate this functioning, a hybrid actuation system by combining the larger bandwidth feature of piezoelectric macro-fibre composites and relatively higher work densities of shape memory alloy wires are used. Finite element analysis is applied to optimize piezoelectric actuation of the internal compliant structure. A coupled fluid-surface interaction analysis is conducted on the wing section during morphing to study the development of the velocity boundary layer at low Reynold’s numbers of airflow.

Keywords: compliant mechanism, hybrid morphing, piezoelectrics, shape memory alloys

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Authors: R. Adwaith, J. Gopinath, Vasantha Kohila B., R. Chandru, Arul Prakash R.

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The turbofan engine is a type of air breathing engine that is widely used in aircraft propulsion produces thrust mainly from the mass-flow of air bypassing the engine core. The present research has developed an effective method numerically by increasing the thrust generated from the bypass air. This thrust increase is brought about by heating the walls of the bypass valve from the combustion chamber using convective heat transfer method. It is achieved computationally by the use external heat to enhance the velocity of bypass air of turbofan engines. The bypass valves are either heated externally using multicell tube resistor which convert electricity generated by dynamos into heat or heat is transferred from the combustion chamber. This increases the temperature of the flow in the valves and thereby increase the velocity of the flow that enters the nozzle of the engine. As a result, mass-flow of air passing the core engine for producing more thrust can be significantly reduced thereby saving considerable amount of Jet fuel. Numerical analysis has been carried out on a scaled down version of a typical turbofan bypass valve, where the valve wall temperature has been increased to 700 Kelvin. It is observed from the analysis that, the exit velocity contributing to thrust has significantly increased by 10 % due to the heating of by-pass valve. The degree of optimum increase in the temperature, and the corresponding effect in the increase of jet velocity is calculated to determine the operating temperature range for efficient increase in velocity. The technique used in the research increases the thrust by using heated by-pass air without extracting much work from the fuel and thus improve the efficiency of existing turbofan engines. Dimensional analysis has been carried to prove the accuracy of the results obtained numerically.

Keywords: turbofan engine, bypass valve, multi-cell tube, convective heat transfer, thrust

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Authors: Farah Naja, Mohamad Alameddine

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Background: The difficulty of compliance to therapeutic and lifestyle management of type 2 diabetes mellitus (T2DM) encourages patients to use complementary and alternative medicine (CAM) therapies. Little is known about the prevalence and mode of CAM use among diabetics in the Eastern Mediterranean Region in general and Lebanon in particular. Objective: To assess the prevalence and modes of CAM use among patients with T2DM residing in Beirut, Lebanon. Methods: A cross-sectional survey of T2DM patients was conducted on patients recruited from two major referral centers - a public hospital and a private academic medical center in Beirut. In a face-to-face interview, participants completed a survey questionnaire comprised of three sections: socio-demographic, diabetes characteristics and types and modes of CAM use. Descriptive statistics, univariate and multivariate logistic regression analyses were utilized to assess the prevalence, mode and correlates of CAM use in the study population. The main outcome in this study (CAM use) was defined as using CAM at least once since diagnosis with T2DM. Results: A total of 333 T2DM patients completed the survey (response rate: 94.6%). Prevalence of CAM use in the study population was 38%, 95% CI (33.1-43.5). After adjustment, CAM use was significantly associated with a “married” status, a longer duration of T2DM, the presence of disease complications, and a positive family history of the disease. Folk foods and herbs were the most commonly used CAM followed by natural health products. One in five patients used CAM as an alternative to conventional treatment. Only 7 % of CAM users disclosed the CAM use to their treating physician. Health care practitioners were the least cited (7%) as influencing the choice of CAM among users. Conclusion: The use of CAM therapies among T2DM patients in Lebanon is prevalent. Decision makers and care providers must fully understand the potential risks and benefits of CAM therapies to appropriately advise their patients. Attention must be dedicated to educating T2DM patients on the importance of disclosing CAM use to their physicians especially patients with a family history of diabetes, and those using conventional therapy for a long time.

Keywords: nutritional supplements, type 2 diabetes mellitus, complementary and alternative medicine (CAM), conventional therapy

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Authors: Deepak Bhardwaj, Narendra Tuteja

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Global climate change is impacting large agrarian societies, especially those in countries located near the equator. Agriculture, and consequently, plant-based food, is the hardest hit in tropical and sub-tropical countries such as India due to an increased incidence of drought as well as an increase in soil salinity. One method that holds promise is AMF-rich biofertilizers which assist in activating proteins which in turn help alleviate abiotic stress in plants. In the present study, we identified two important species of (arbuscular mycorrhizal fungus) AMF belonging to Glomus and Gigaspora from the rhizosphere of the important medicinal plant Justicia adathoda. These two species have been found to be responsible for the abundance of Justicia adathoda in the semi-arid areas of the Jammu valley located in northern India, namely, the Union Territory of Jammu and Kashmir. We isolated the species of Glomus and Gigaspora from the rhizosphere of Justicia adathoda and used them as biofertilizers for the tomato plant. Significant improvements in the growth parameters were observed in the tomato plants inoculated with Glomus sp. and Gigaspora sp. in comparison with the tomato plants that were grown without AMF treatments. Tomato plants grown along with Glomus sp. and Gigaspora sp. have been observed to withstand 200 mM of salinity and 25% PEG stress. AMF also resulted in an increased concentration of proline and antioxidant enzymes in tomato plants. We also examined the expression levels of salinity and drought stress-inducible genes such as pea DNA helicase 45 (PDH 45) and genes of G-protein subunits of the tomato plants inoculated with and without AMF under stress and normal conditions. All the stress-inducible genes showed a significant increase in their gene expression under stress and AMF inoculation, while their levels were found to be normal under AMF inoculation without stress. We propose a model of abiotic stress alleviation in tomato plants with the help of external factors such as AMF and internally with the help of proteins like PDH 45 and G-proteins.

Keywords: AMF, abiotic stress, g-proteins, PDH-45

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Authors: Suman Dutta, Manish Agrawal, C. S. Jog

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Accurate computation of hydrodynamic forces on floating structures and their deformation finds application in the ocean and naval engineering and wave energy harvesting. This manuscript presents a monolithic, finite element strategy for fluid-structure interaction involving hyper-elastic solids partly submerged in an incompressible fluid. A velocity-based Arbitrary Lagrangian-Eulerian (ALE) formulation has been used for the fluid and a displacement-based Lagrangian approach has been used for the solid. The flexibility of the ALE technique permits us to treat the free surface of the fluid as a Lagrangian entity. At the interface, the continuity of displacement, velocity and traction are enforced using the mortar method. In the mortar method, the constraints are enforced in a weak sense using the Lagrange multiplier method. In the literature, the mortar method has been shown to be robust in solving various contact mechanics problems. The time-stepping strategy used in this work reduces to the generalized trapezoidal rule in the Eulerian setting. In the Lagrangian limit, in the absence of external load, the algorithm conserves the linear and angular momentum and the total energy of the system. The use of monolithic coupling with an energy-conserving time-stepping strategy gives an unconditionally stable algorithm and allows the user to take large time steps. All the governing equations and boundary conditions have been mapped to the reference configuration. The use of the exact tangent stiffness matrix ensures that the algorithm converges quadratically within each time step. The robustness and good performance of the proposed method are demonstrated by solving benchmark problems from the literature.

Keywords: ALE, floating body, fluid-structure interaction, monolithic, mortar method

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Authors: Sharda Kumari

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As the Covid-19 pandemic continues to leave its mark on the global business landscape, companies have had to adapt to new realities and find ways to sustain their operations amid social distancing measures, government restrictions, and heightened public health concerns. This unprecedented situation has placed considerable stress on both employees and employers, underscoring the need for innovative approaches to manage the risks associated with Covid-19 transmission in the workplace. In response to these challenges, the pandemic has accelerated the adoption of digital technologies, with an increasing preference for remote interactions and virtual collaboration. Customer relationship management (CRM) systems have risen to prominence as a vital resource for organizations navigating the post-pandemic world, providing a range of benefits that include acquiring new customers, generating insightful consumer data, enhancing customer relationships, and growing market share. In the context of pandemic management, CRM systems offer three primary advantages: (1) integration features that streamline operations and reduce the need for multiple, costly software systems; (2) worldwide accessibility from any internet-enabled device, facilitating efficient remote workforce management during a pandemic; and (3) the capacity for rapid adaptation to changing business conditions, given that most CRM platforms boast a wide array of remotely deployable business growth solutions, a critical attribute when dealing with a dispersed workforce in a pandemic-impacted environment. These advantages highlight the pivotal role of CRM systems in helping organizations remain resilient and adaptive in the face of ongoing global challenges.

Keywords: healthcare, CRM, customer relationship management, customer experience, digital transformation, pandemic response, patient monitoring, patient management, healthcare automation, electronic health record, patient billing, healthcare information systems, remote workforce, virtual collaboration, resilience, adaptable business models, integration features, CRM in healthcare, telehealth, pandemic management

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Authors: Ankit Kumar Yadav, Nagendra R. Velaga

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Driving under the influence of alcohol impairs the driving performance and increases the crash risks worldwide. The present study investigated the effect of different Blood Alcohol Concentrations (BAC) on the accelerating and braking behaviour of drivers with the help of driving simulator experiments. Eighty-two licensed Indian drivers drove on the rural road environment designed in the driving simulator at BAC levels of 0.00%, 0.03%, 0.05%, and 0.08% respectively. Driving performance was analysed with the help of vehicle control performance indicators such as mean acceleration and mean brake pedal force of the participants. Preliminary analysis reported an increase in mean acceleration and mean brake pedal force with increasing BAC levels. Generalized linear mixed models were developed to quantify the effect of different alcohol levels and explanatory variables such as driver’s age, gender and other driver characteristic variables on the driving performance indicators. Alcohol use was reported as a significant factor affecting the accelerating and braking performance of the drivers. The acceleration model results indicated that mean acceleration of the drivers increased by 0.013 m/s², 0.026 m/s² and 0.027 m/s² for the BAC levels of 0.03%, 0.05% and 0.08% respectively. Results of the brake pedal force model reported that mean brake pedal force of the drivers increased by 1.09 N, 1.32 N and 1.44 N for the BAC levels of 0.03%, 0.05% and 0.08% respectively. Age was a significant factor in both the models where one year increase in drivers’ age resulted in 0.2% reduction in mean acceleration and 19% reduction in mean brake pedal force of the drivers. It shows that driving experience could compensate for the negative effects of alcohol to some extent while driving. Female drivers were found to accelerate slower and brake harder as compared to the male drivers which confirmed that female drivers are more conscious about their safety while driving. It was observed that drivers who were regular exercisers had better control on their accelerator pedal as compared to the non-regular exercisers during drunken driving. The findings of the present study revealed that drivers tend to be more aggressive and impulsive under the influence of alcohol which deteriorates their driving performance. Drunk driving state can be differentiated from sober driving state by observing the accelerating and braking behaviour of the drivers. The conclusions may provide reference in making countermeasures against drinking and driving and contribute to traffic safety.

Keywords: alcohol, acceleration, braking behaviour, driving simulator

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Authors: Sheraz Gul

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The requirements for progressing a compound to clinical trials is well established and relies on the results from in-vitro and in-vivo animal tests to indicate that it is likely to be safe and efficacious when testing in humans. The typical data package required will include demonstrating compound safety, toxicity, bioavailability, pharmacodynamics (potential effects of the compound on body systems) and pharmacokinetics (how the compound is potentially absorbed, distributed, metabolised and eliminated after dosing in humans). If the desired criteria are met and the compound meets the clinical Candidate criteria and is deemed worthy of further development, a submission to regulatory bodies such as the US Food & Drug Administration for an exploratory Investigational New Drug Study can be made. The purpose of this study is to collect data to establish that the compound will not expose humans to unreasonable risks when used in limited, early-stage clinical studies in patients or normal volunteer subjects (Phase I). These studies are also designed to determine the metabolism and pharmacologic actions of the drug in humans, the side effects associated with increasing doses, and, if possible, to gain early evidence on their effectiveness. In order to reach the above goals, we have developed a pre-clinical high throughput Absorption, Distribution, Metabolism and Excretion–Toxicity (ADME–Toxicity) panel of assays to identify compounds that are likely to meet the Lead and Candidate compound acceptance criteria. This panel includes solubility studies in a range of biological fluids, cell viability studies in cancer and primary cell-lines, mitochondrial toxicity, off-target effects (across the kinase, protease, histone deacetylase, phosphodiesterase and GPCR protein families), CYP450 inhibition (5 different CYP450 enzymes), CYP450 induction, cardio-toxicity (hERG) and gene-toxicity. This panel of assays has been applied to multiple compound series developed in a number of projects delivering Lead and clinical Candidates and examples from these will be presented.

Keywords: absorption, distribution, metabolism and excretion–toxicity , drug discovery, food and drug administration , pharmacodynamics

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