Search results for: drug safety

Authors: E. Batista, R. Mendes, A. Furtado, M. C. Ferreira, I. Godinho, J. A. Sousa, M. Alvares, R. Martins

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Syringe pumps are commonly used for drug delivery in hospitals and clinical environments. These instruments are critical in neonatology and oncology, where any variation in the flow rate and drug dosing quantity can lead to severe incidents and even death of the patient. Therefore it is very important to determine the accuracy and precision of these devices using the suitable calibration methods. The Volume Laboratory of the Portuguese Institute for Quality (LVC/IPQ) uses two different methods to calibrate syringe pumps from 16 nL/min up to 20 mL/min. The Interferometric method uses an interferometer to monitor the distance travelled by a pusher block of the syringe pump in order to determine the flow rate. Therefore, knowing the internal diameter of the syringe with very high precision, the travelled distance, and the time needed for that travelled distance, it was possible to calculate the flow rate of the fluid inside the syringe and its uncertainty. As an alternative to the gravimetric and the interferometric method, a methodology based on the application of optical technology was also developed to measure flow rates. Mainly this method relies on measuring the increase of volume of a drop over time. The objective of this work is to compare the results of the calibration of two syringe pumps using the different methodologies described above. The obtained results were consistent for the three methods used. The uncertainties values were very similar for all the three methods, being higher for the optical drop method due to setup limitations.

Keywords: calibration, flow, interferometry, syringe pump, uncertainty

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Authors: Ali Asmari, Alex Symington, Htaik Than, Austin Caradonna, John Senft

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This paper presents the collaborative effort between ULC Technologies and Con Edison in developing a groundbreaking robotic cable splicing machine. The focus is on the machine's design, which integrates advanced robotics and automation to enhance safety and efficiency in power network maintenance. The paper details the operational steps of the machine, including cable grounding, cutting, and removal of different insulation layers, and discusses its novel technological approach. The significant benefits over traditional methods, such as improved worker safety and reduced outage times, are highlighted based on the field data collected during the validation phase of the project. The paper also explores the future potential and scalability of this technology, emphasizing its role in transforming the landscape of power network maintenance.

Keywords: cable splicing machine, power network maintenance, electric distribution, electric transmission, medium voltage cable

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Authors: Genevieve D. Fernandes, Nisha P. Naik

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All through the ages in all human civilizations, men have been engaged in construction activity, not only to build their dwellings and house their activities, but also roads, bridges to facilitate means of transport, and communication etc. The main concern in this activity was to ensure safety and reduce the collapse of the buildings and other structures. But even after taking all precautions, it is impossible to guarantee safety and collapse because of several unforeseen reasons like faulty constructions, design errors, overloading, soil liquefaction, gas explosion, material degradation, terrorist attacks and economic factors also contributing to the collapse. It is also uneconomical to design the structure for unforeseen events unless they have a reasonable chance of occurrence. In order to ensure safety and prevent collapse, many guidelines have been framed by local bodies and government authorities in many countries like the United States Department of Defence (DOD), United States General Service Administration (GSA) and Euro-Codes in European Nations. Some other practices are followed to incorporate redundancies in the structure like detailing, ductile designs, tying of elements at particular locations, and provision of hinges and interconnections. It is also to be admitted that a full-proof safe design structure for accidental events cannot be prepared and implemented as it is uneconomical and the chances of such occurrences are less. This paper reviews past case studies of the collapse of structures with the aim of developing an understanding of the collapse mechanism. This study will definitely help to bring about a detailed improvement in the design to maximise the quality of the construction at a minimal cost.

Keywords: unforeseen factors, progressive collapse, collapse resisting mechanisms, column removal scenario

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Authors: A. Ardianto, M. A. Putera Agung, S. Pramusandi

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Power waterway is one of dam structures and as an intake vertical tunnel or well function for hydroelectric power plants in Jatigede area, Sumedang, West Java. Gate shaft is also one of parts the power waterway system. The paper concerns some consideration in determining a critical state parameter on the back stability analysis of gate shaft or excavation wall stability during excavation. Study analysis was carried out using without and with reinforcement system. Results study showed that reinforcement shaft could reduce the total displacement and safety factor could increases significantly. Based on the back calculation results, it was recommended to install some reinforcement materials and drainage system to reduce pore water pressure.

Keywords: power waterway, reinforcement, displacement, safety

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Authors: Xin-Yu Li, Dung-Ying Lin

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Fleet availability is a crucial indicator for an aircraft fleet. However, in practice, fleet planning involves many resource and safety constraints, such as annual and monthly flight training targets and maximum engine usage limits. Due to safety considerations, engines must be removed for mandatory maintenance and replacement of key components. This situation is known as the "threshold." The annual number of thresholds is a key factor in maintaining fleet availability. However, the traditional method heavily relies on experience and manual planning, which may result in ineffective engine usage and affect the flight missions. This study aims to address the challenges of fleet planning and availability maintenance in aircraft fleets with resource and safety constraints. The goal is to effectively optimize engine usage and maintenance tasks. This study has four objectives: minimizing the number of engine thresholds, minimizing the monthly lack of flight hours, minimizing the monthly excess of flight hours, and minimizing engine disassembly frequency. To solve the resulting formulation, this study uses parametric programming techniques and ϵ-constraint method to reformulate multi-objective problems into single-objective problems, efficiently generating Pareto fronts. This method is advantageous when handling multiple conflicting objectives. It allows for an effective trade-off between these competing objectives. Empirical results and managerial insights will be provided.

Keywords: aircraft fleet, engine utilization planning, multi-objective optimization, parametric method, Pareto optimality

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Authors: R. H. Bustos, L. Martinez, J. García, F. Suárez

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MRP1 (Multi-drug resistance associated protein 1) and MRP2 (Multi-drug resistance associated protein 2) are two proteins belonging to the transporters of ABC (ATP-Binding Cassette). These transporter proteins are involved in the efflux of several biological drugs and xenobiotic and also in multiple physiological, pathological and pharmacological processes. Evidence has been found that there is a correlation among different polymorphisms found and their clinical implication in the resistance to antiepileptic, chemotherapy and anti-infectious drugs. In our study, exonic regions of MRP1/ABCC1 y MRP2/ABCC2 were studied in the Colombian population, specifically in the region of the central Savannah (Cundinamarca) to determinate SNP (Single Nucleotide Polymorphisms) and determinate its allele frequency and its genomics frequency. Results showed that for our population, SNP are found that have been previously reported for MRP1/ABCC1 (rs200647436, rs200624910, rs150214567) as well as for MRP2/ABCC2 (rs2273697, rs3740066, rs142573385, rs17216212). In addition, 13 new SNP were identified. Evidences show an important clinic correlation for polymorphisms rs3740066 and rs2273697. The study object population displays genetic variability as compared to the one reported in other populations.

Keywords: ATP-binding cassette (ABCC), Colombian population, multidrug-resistance protein (MRP), pharmacogenetic, single nucleotide polymorphism (SNP)

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Authors: Ikah Ning Prasetiowati Permanasari, Gunawan Handayani, Lilik Hendrajaya

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Landslide occurence at Mukapayung, Cililin West Java with material movement downward slope as far as 500m and hit residential areas of the village Nagrog cause eighteen people died and ten homes were destroyed and twenty-three heads of families evacuated. In order to test the hypothesis that soil at the landslides area is prone to landslides, we do drilling and the following tests were taken: particle size distribution, atterberg limits, shear strength, density, shringkage limits and triaxial unconsolidated and consolidated undrained test. Factor of safety was calculated to find out the possibility of subsequent landslides. The value of FOS of three layers is 1,05 which means that the soil in a critical condition and would be imminent to slide if there is disruption from the outside.

Keywords: atterberg limits, particle size distribution, shear strength parameters, slope geometry, factor of safety

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Authors: Veronika Sharok

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Research relevance on psychological determinants of risky behaviors is caused by high prevalence of such behaviors, particularly among youth. Risky sexual behavior, including unprotected and casual sex, frequent change of sexual partners, drug and alcohol use lead to negative social consequences and contribute to the spread of HIV infection and other sexually transmitted diseases. Data were obtained from 302 respondents aged 15-35 which were divided into 3 empirical groups: persons prone to risky sexual behavior, drug users and alcohol users; and 3 control groups: the individuals who are not prone to risky sexual behavior, persons who do not use drugs and the respondents who do not use alcohol. For processing, we used the following methods: Qualitative method for nominative data (Chi-squared test) and quantitative methods for metric data (student's t-test, Fisher's F-test, Pearson's r correlation test). Statistical processing was performed using Statistica 6.0 software. The study identifies two groups of factors that prevent risky behaviors. Internal factors, which include the moral and value attitudes; significance of existential values: love, life, self-actualization and search for the meaning of life; understanding independence as a responsibility for the freedom and ability to get attached to someone or something up to a point when this relationship starts restricting the freedom and becomes vital; awareness of risky behaviors as dangerous for the person and for others; self-acknowledgement. External factors (prevent risky behaviors in case of absence of the internal ones): absence of risky behaviors among friends and relatives; socio-demographic characteristics (middle class, marital status); awareness about the negative consequences of risky behaviors; inaccessibility to psychoactive substances. These factors are common for proneness to each type of risky behavior, because it usually caused by the same reasons. It should be noted that if prevention of risky behavior is based only on elimination of external factors, it is not as effective as it may be if we pay more attention to internal factors. The results obtained in the study can be used to develop training programs and activities for prevention of risky behaviors, for using values preventing such behaviors and promoting healthy lifestyle.

Keywords: existential values, prevention, psychological features, risky behavior

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Authors: Sallama Resen, Celal Öztürk

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Distance estimation between tow nodes has wide scope of surveillance and tracking applications. This paper suggests a Bluetooth Low Energy (BLE) technology as a media for transceiver and receiver signal in small indoor areas. As an example, BLE communication technologies used in child safety domains. Local network is designed to detect child position in indoor school area consisting Mobile Beacons (MB), Access Points (AP) and Smart Phones (SP) where MBs stuck in children’s shoes as wearable sensors. This paper presents a technique that can detect mobile beacons’ position and help finding children’s location within dynamic environment. By means of bluetooth beacons that are attached to child’s shoes, the distance between the MB and teachers SP is estimated with an accuracy of less than one meter. From the simulation results, it is shown that high accuracy of position coordinates are achieved for multi-mobile beacons in different environments.

Keywords: bluetooth low energy, child safety, mobile beacons, received signal strength

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Authors: Hyeon Jong Yoo, Jae Hwan Yang, Dong Kyu Kim

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Recently, riding a bicycle is recommended as an eco-friendly means of transportation. In Seoul, the mayor has secured budget for extending bicycle infrastructure. As bicycle rental centers are adopted in places, more citizens are using bike rental service on bike-only roads for leisure. However, most of the citizens are not experienced in riding bicycles. They usually do not wear helmets, keep the balance of bicycle riding, and pay attention to nearby occasions. Therefore, in this study, bicycles on Han-river bike-only road were tracked, and their behaviors were analyzed in order to show how dangerously beginner riders are riding. The number of conflicts is calculated to evaluate riding safety on the most crowded bike-only road. As a result, conflicts between beginner riders and fast-driving skilled drivers are frequently observed especially at night, and on weekends. In conclusion, it is suggested that the government should acknowledge citizens the fact that bikes are vehicles and adopt a test for bike driving.

Keywords: bicycles, safety, bike-only road, policy proposal

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Authors: Marzena Półka, Bożena Kukfisz

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This paper presents an analysis of dust explosion hazards in the process industries. It includes selected testing method of dust explosibility and presentation two of them according to experimental standards used by Department of Combustion and Fire Theory in The Main School of Fire Service in Warsaw. In the article are presented values of maximum acceptable surface temperature (MAST) of machines operating in the presence of dust cloud and chosen dust layer with thickness of 5 and 12,5mm. The comparative analysis, points to the conclusion that the value of the minimum ignition temperature of the layer (MITL) and the minimum ignition temperature of dust cloud (MTCD) depends on the granularity of the substance. Increasing the thickness of the dust layer reduces minimum ignition temperature of dust layer. Increasing the thickness of dust at the same time extends the flameless combustion and delays the ignition.

Keywords: fire safety engineering, industrial hazards, minimum ignition temperature, wood dust

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Authors: Kenza Maher, Yahya Zakaria, Noora S. Al-Jaidah

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Temperature is a critical parameter for lithium-ion battery performance, life, and safety. In this study, four commercially available 18650 lithium-ion cells from four different manufacturers are subjected to accelerated cycle aging for up to 500 cycles at two different temperatures (25°C and 45°C). The cells are also calendar-aged at the same temperatures in both charged and discharged states for 6 months to investigate the effect of aging and temperature on capacity fade and state of health. The results showed that all battery cells demonstrated good cyclability and had a good state of health at both temperatures. However, the capacity loss and state of health of these cells are found to be dependent on the cell chemistry and aging conditions, including temperature. Specifically, the capacity loss is found to be higher at the higher aging temperature, indicating the significant impact of temperature on the aging of lithium-ion batteries.

Keywords: lithium-ion battery, aging mechanisms, cycle aging, calendar aging.

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Authors: Olivier Chaigneau, Damianos Oikonomidis, Marie-Cecile Delmas

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GAMBAS (Galileo Advanced features for the Maritime domain: Breakthrough Applications for Safety and security) is a project funded by the European Space Program Agency (EUSPA) aiming at identifying the search-and-rescue and ship security alert system needs for maritime users (including operators and fishing stakeholders) and developing operational concepts to answer these needs. The general objective of the GAMBAS project is to support the deployment of Galileo exclusive features in the maritime domain in order to improve safety and security at sea, detection of illegal activities and associated surveillance means, resilience to natural and human-induced emergency situations, and develop, integrate, demonstrate, standardize and disseminate these new associated capabilities. The project aims to demonstrate: improvement of the SAR (Search And Rescue) and SSAS (Ship Security Alert System) detection and response to maritime distress through the integration of new features into the beacon for SSAS in terms of cost optimization, user-friendly aspects, integration of Galileo and OS NMA (Open Service Navigation Message Authentication) reception for improved authenticated localization performance and reliability, and at sea triggering capabilities, optimization of the responsiveness of RCCs (Rescue Co-ordination Centre) towards the distress situations affecting vessels, the adaptation of the MCCs (Mission Control Center) and MEOLUT (Medium Earth Orbit Local User Terminal) to the data distribution of SSAS alerts.

Keywords: Galileo new advanced features, maritime, safety, security

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Authors: Emad Heydarnia, Aref Sepasi, Nika Asefi, Sara Khakshournia, Javad Mohammadnejad

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Background: Despite breakthrough therapeutics in breast cancer, it is one of the main causes of mortality among women worldwide. Thus, drug therapies for treating breast cancer have recently been developed by scientists. Metformin and Sorafenib are well-known therapeutic in breast cancer. In the present study, we combined Sorafenib and PCL-sorafenib with metformin to improve drug absorption and promote therapeutic efficiency. Methods: The MCF-7 cells were treated with Metformin, Sorafenib, or PCL-sorafenib. The growth inhibitory effect of these drugs and cell viability were assessed using MTT and flow cytometry assays, respectively. The expression of targeted genes involved in cell proliferation, signaling, and the cell cycle was measured by Real-time PCR. Results: The results showed that MCF-7 cells treated with Metformin/Sorafenib and PCL-sorafenib/Metformin co-treatment contributed to 50% viability compared to untreated group. Moreover, PI and Annexin V staining tests showed that the cells viability for Metformin/Sorafenib and PCL-sorafenib/Metformin was 38% and 17%, respectively. Furthermore, Sorafenib/Metformin and PCL-sorafenib/Metformin leads to p53 gene expression increase by which they can increase ROS, thereby decreasing GPX4 gene expression. In addition, they affected the expression of BCL2, and BAX genes and altered the cell cycle. Conclusion: Together, the combination of PCL-sorafenib/Metformin and Sorafenib/Metformin increased Sorafenib absorption at lower doses and also leads to apoptosis and oxidative stress increases in MCF-7 cells.

Keywords: breast cancer, metformin, nanotechnology, sorafenib

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Authors: Kai-Cheng Hsu, Tzu-Ying Sung, Jinn-Moon Yang

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Colorectal cancer (CRC) is one of the main causes of cancer death in the world. Although several drugs have been developed to treat colorectal cancer, such as Regorafenib and 5-FU, their efficacy is often limited by the development of drug resistance. Therefore, development of new drugs with new scaffolds is necessary to treat CRC. Here, we used site-moiety maps to identify inhibitors against PIM1, LIMK1, SRC, and mTOR, which are often overexpressed in CRC. A site-moiety map represents physicochemical properties and moiety preferences of a binding site through anchors. An anchor contains three elements: (1) conserved interacting residues of a binding pocket; (2) moiety preference of the binding pocket; and (3) the type (e.g., hydrogen-bonding or van der Waals interactions) of interaction between the moieties and the binding pocket. Then, we performed a structure-based virtual screening of ~260,000 compounds and selected compound candidates with high site-moiety map scores for bioassays. Among these candidates, compound 1 and compound 2 inhibited the growth of CRC cells with IC50 values of <10 μM. The experimental result of enzyme-based assays indicated that compound 1 is a dual inhibitor against PIM1 (IC50 6 μM) and LIMK1(IC50 11 μM). Compound 2 was predicted as a SRC inhibitor and will be further validated. The compounds inhibited different protein targets compared to the current drugs. We believe that the compounds provide a starting point to design new drugs for CRC treatment.

Keywords: colorectal cancer, drug discovery, site-moiety map, virtual screening, PIM1, LIMK1

Procedia PDF Downloads 247

Authors: Ching-Sung Wang, Teng-Wei Wang, Zhen-Ting Zheng

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This study mainly concerns a safety device designed for child care. When children are out of sight or the caregivers cannot always pay attention to the situation, through the functions of this device, caregivers can immediately be informed to make sure that the children do not get lost or hurt, and thus, ensure their safety. Starting from this concept, a device is produced based on the relatively low-cost Bluetooth piconet system and a three-axis gyroscope sensor. This device can transmit data to a mobile phone app through Bluetooth, in order that the user can learn the situation at any time. By simply clipping the device in a pocket or on the waist, after switching on/starting the device, it will send data to the phone to detect the child’s fall and distance. Once the child is beyond the angle or distance set by the app, it will issue a warning to inform the phone owner.

Keywords: children care, piconet system, three-axis gyroscope, distance detection, falls detection

Procedia PDF Downloads 598

Authors: Adepoju A. A., Raufu M. O., Ganiyu M. O., Olawuyi S. O., Olalere J. O., Ogunkunle A. A.

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This study investigated the effects of social safety nets on food security among farming households in Southwest Nigeria. The study used a multistage sampling technique, purposively selecting two states from southwest Nigeria, Oyo and Ogun as the study area with eight Agricultural Development Programme (ADP) agricultural zones. The Local Government Areas (LGAs) were stratified into urban and rural LGAs. Sixteen villages from Oyo and 12 villages from Ogun were randomly selected from the rural LGAs using a proportionate to-size sampling, resulting in 472 respondents, with 271 and 201 from Oyo and Ogun states, respectively. The data was analyzed using descriptive statistics like mean, standard deviation, frequency and percentages, while logistic regression analysis examines the association between independent variables and dependent variables. The study found that poverty reduction, social empowerment, food security palliative, microcredit, and agricultural empowerment are the most prevalent social safety nets among farming households. School feed programs are the most prevalent form of poverty reduction, while training for empowerment improves wellbeing. Food item distribution is the most beneficial for food security and wellbeing. Self-empowerment-based micro-credit support is the most effective, while Anchor Borrower's project is the most beneficial for agricultural empowerment. The study found that 62.68% of the variance in food security status is explained by independent variables. females farmers have a 56% higher likelihood of being food secure than their male counterparts. An additional increase in age decreases the likelihood of being food secure by 6%. Married individuals have a 58% lower likelihood of being food secure compared to singles, possibly due to increased financial responsibilities. A larger household size increases the likelihood of being food secure by 3.41%. Larger households may benefit from economies of scale or shared resources and social safety net programs. Engagement in farming as a primary occupation increases the likelihood of being food secure by 62%. The study further reveals that participation in poverty reduction and microcredit programs significantly increases the likelihood of food security by 30,069% and 135.48%, respectively. The study therefore recommends expanding school feed programs, improving empowerment training, strengthening food distribution, promoting micro-credit, supporting agricultural empowerment, and addressing gender disparities in social safety net programs.

Keywords: poverty reduction, food distribution, micro-credit, household well-being

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Authors: Gayan Mapitiya

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Maintaining good occupational health and safety (OHS) performance is significant at the coalface, especially in industries such as mining, power, and construction. Coalface workers are vulnerable to high OHS risks such as working at heights, working with mobile plants and vehicles, working with underground and above ground services, chemical emissions, radiation hazards and explosions at everyday work. To improve OHS performance of workers, OHS key performance indicators (KPIs) (for example, lost time injuries (LTI), serious injury frequency rate (SIFR), total reportable injury frequency rate (TRIFR) and number of near misses) are widely used by managers in making OHS business decisions such as investing in safety equipment and training programs. However, in many organizations, workers at the coalface hardly see any relevance or value addition of OHS KPIs to their everyday work. Therefore, the aim of the study was to understand why coalface workers perceive that OHS KPIs are not practically relevant to their jobs. Accordingly, this study was conducted as a qualitative case study focusing on a large electricity and gas firm in Australia. Semi-structured face to face interviews were conducted with selected coalface workers to gather data on their attitude towards OHS KPIs. The findings of the study revealed that workers at the coalface generally have no understanding of the purpose of KPIs, the meaning of each KPI, origin of KPIs, and how KPIs are correlated to organizational performance. Indeed, KPIs are perceived as ‘meaningless obstacles’ imposed on workers by managers without a rationale. It is recommended to engage coalface workers (a fair number of representatives) in both KPIs setting and revising processes while maintaining a continuous dialogue between workers and managers in regards OHS KPIs.

Keywords: KPIs, coalface, OHS risks, case-study

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Authors: Yasir Memon

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The complexity and challenges in the offshore industry are increasing more than the past. The oil and gas industry is expanding every day by accomplishing these challenges. More challenging wells such as longer and deeper are being drilled in today’s environment. Blowout prevention phenomena hold a worthy importance in oil and gas biosphere. In recent, so many past years when the oil and gas industry was growing drilling operation were extremely dangerous. There was none technology to determine the pressure of reservoir and drilling hence was blind operation. A blowout arises when an uncontrolled reservoir pressure enters in wellbore. A potential of blowout in the oil industry is the danger for the both environment and the human life. Environmental damage, state/country regulators, and the capital investment causes in loss. There are many cases of blowout in the oil the gas industry caused damage to both human and the environment. A huge capital investment is being in used to stop happening of blowout through all over the biosphere to bring damage at the lowest level. The objective of this study is to promote safety and good resources to assure safety and environmental integrity in all operations during drilling. This study shows that human errors and management failure is the main cause of blowout therefore proper management with the wise use of precautions, prevention methods or controlling techniques can reduce the probability of blowout to a minimum level. It also discusses basic procedures, concepts and equipment involved in well control methods and various steps using at various conditions. Furthermore, another aim of this study work is to highlight management role in oil gas operations. Moreover, this study analyze the causes of Blowout of Macondo well occurred in the Gulf of Mexico on April 20, 2010, and deliver the recommendations and analysis of various aspect of well control methods and also provides the list of mistakes and compromises that British Petroleum and its partner were making during drilling and well completion methods and also the Macondo well disaster happened due to various safety and development rules violation. This case study concludes that Macondo well blowout disaster could be avoided with proper management of their personnel’s and communication between them and by following safety rules/laws it could be brought to minimum environmental damage.

Keywords: energy, environment, oil and gas industry, Macondo well accident

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Authors: K. R. Thabethe, G. A. Adefolaju, M. J. Hosie

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Cervical cancer is the third most commonly diagnosed cancer globally and it is one of three AIDS defining malignancies. Highly active antiretroviral therapy (HAART) is a combination of three or more antiretroviral drugs and has been shown to play a significant role in reducing the incidence of some AIDS defining malignancies, although its effect on cervical cancer is still unclear. The aim of this study was to investigate the relationship between cervical cancer and HAART. This was achieved by studying the expression of two signalling molecules expressed in cervical cancer; MUC1 and P65. Following the 24 hour treatment of a cervical cancer cell line, HCS-2, with drugs which are commonly used as part of HAART at their clinical plasma concentrations, real-time qPCR and immunofluorescence were used in order to study gene and protein expression. A one way ANOVA followed by a Tukey Kramer Post Hoc test was conducted using JMP 11 software on both sets of data. The drug classified as a protease inhibitor (PI) (i.e. LPV/r) reduced MUC1 and P65 gene and protein expression more than the other drug tested. PIs are known to play a significant role in cell death, therefore the cells were thought to be more susceptible to cell death following treatment with PIs. In conclusion, the drugs used, especially the PI showed some anticancer effects by facilitating cell death through decreased gene and protein expression of MUC1 and P65 and present promising agents for cancer treatment.

Keywords: cervical cancer, haart, MUC1, P65

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Authors: Vichayada Laohapiboolkul

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Introduction: As the legal use of cannabis is being widely accepted throughout the world, medical cannabis has been explored in order to become an alternative cure for patients. Tetrahydrocannabinol (THC) and Cannabidiol (CBD) are natural cannabinoids found in the Cannabis plant which is proved to have positive treatment for various diseases and symptoms such as chronic pain, neuropathic pain, spasticity resulting from multiple sclerosis, reduce cancer-associated pain, autism spectrum disorders (ASD), dementia, cannabis and opioid dependence, psychoses/schizophrenia, general social anxiety, posttraumatic stress disorder, anorexia nervosa, attention-deficit hyperactivity disorder, and Tourette's disorder. Regardless of all the medical benefits, THC, if not metabolized, can lead to mild up to severe adverse drug reactions (ADR). The enzyme CYP2C19 was found to be one of the metabolizers of THC. However, the suballele CYP2C19*2 manifests as a poor metabolizer which could lead to higher levels of THC than usual, possibly leading to various ADRs. Objective: The aim of this study was to investigate the distribution of CYP2C19, specifically CYP2C19*2, genes in Thai patients treated with medical cannabis along with adverse drug reactions. Materials and Methods: Clinical data and EDTA whole blood for DNA extraction and genotyping were collected from patients for this study. CYP2C19*2 (681G>A, rs4244285) genotyping was conducted using the Real-time PCR (ABI, Foster City, CA, USA). Results: There were 42 medical cannabis-induced ADRs cases and 18 medical cannabis tolerance controls who were included in this study. A total of 60 patients were observed where 38 (63.3%) patients were female and 22 (36.7%) were male, with a range of age approximately 19 - 87 years. The most apparent ADRs for medical cannabis treatment were dry mouth/dry throat (76.7%), followed by tachycardia (70%), nausea (30%) and a few arrhythmias (10%). In the total of 27 cases, we found a frequency of 18 CYP2C19*1/*1 alleles (normal metabolizers, 66.7%), 8 CYP2C19*1/*2 alleles (intermediate metabolizers, 29.6%) and 1 CYP2C19*2/*2 alleles (poor metabolizers, 3.7%). Meanwhile, 63.6% of CYP2C19*1/*1, 36.3% and 0% of CYP2C19*1/*2 and *2/*2 in the tolerance controls group, respectively. Conclusions: This is the first study to confirm the distribution of CYP2C19*2 allele and the prevalence of poor metabolizer genes in Thai patients who received medical cannabis for treatment. Thus, CYP2C19 allele might serve as a pharmacogenetics marker for screening before initiating treatment.

Keywords: medical cannabis, adverse drug reactions, CYP2C19, tetrahydrocannabinol, poor metabolizer

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Authors: Akanksha Bhatnagar, Sandhya Kortegare, Felice Elefant

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Context: Alzheimer's disease (AD) is a neurodegenerative disorder that is characterized by progressive cognitive decline and memory loss. The cause of AD is not fully understood, but it is thought to be caused by a combination of genetic, environmental, and lifestyle factors. One of the hallmarks of AD is the loss of neurons in the hippocampus, a brain region that is important for memory and learning. This loss of neurons is thought to be caused by a decrease in histone acetylation, which is a process that regulates gene expression. Research Aim: The research aim of the study was to develop mall molecule compounds that can enhance the activity of Tip60, a histone acetyltransferase that is important for memory and learning. Methodology/Analysis: The researchers used in silico structural modeling and a pharmacophore-based virtual screening approach to design and synthesize small molecule compounds strongly predicted to target and enhance Tip60’s HAT activity. The compounds were then tested in vitro and in vivo to assess their ability to enhance Tip60 activity and rescue cognitive deficits in AD models. Findings: The researchers found that several of the compounds were able to enhance Tip60 activity and rescue cognitive deficits in AD models. The compounds were also developed to cross the blood-brain barrier, which is an important factor for the development of potential AD therapeutics. Theoretical Importance: The findings of this study suggest that Tip60 HAT activators have the potential to be developed as therapeutic agents for AD. The compounds are specific to Tip60, which suggests that they may have fewer side effects than other HDAC inhibitors. Additionally, the compounds are able to cross the blood-brain barrier, which is a major hurdle for the development of AD therapeutics. Data Collection: The study collected data from a variety of sources, including in vitro assays and animal models. The in vitro assays assessed the ability of compounds to enhance Tip60 activity using histone acetyltransferase (HAT) enzyme assays and chromatin immunoprecipitation assays. Animal models were used to assess the ability of the compounds to rescue cognitive deficits in AD models using a variety of behavioral tests, including locomotor ability, sensory learning, and recognition tasks. The human clinical trials will be used to assess the safety and efficacy of the compounds in humans. Questions: The question addressed by this study was whether Tip60 HAT activators could be developed as therapeutic agents for AD. Conclusions: The findings of this study suggest that Tip60 HAT activators have the potential to be developed as therapeutic agents for AD. The compounds are specific to Tip60, which suggests that they may have fewer side effects than other HDAC inhibitors. Additionally, the compounds are able to cross the blood-brain barrier, which is a major hurdle for the development of AD therapeutics. Further research is needed to confirm the safety and efficacy of these compounds in humans.

Keywords: Alzheimer's disease, cognition, neuroepigenetics, drug discovery

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Authors: Ayse Gul Bilen

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Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed antidepressants that are used clinically for the treatment of anxiety disorders, obsessive-compulsive disorder (OCD), panic disorders and eating disorders. The first SSRI, fluoxetine (sold under the brand names Prozac and Sarafem among others), had an adverse effect profile better than any other available antidepressant when it was introduced because of its selectivity for serotonin receptors. They have been considered almost free of side effects and have become widely prescribed, however questions about the safety and tolerability of SSRIs have emerged with their continued use. Most SSRI side effects are dose-related and can be attributed to serotonergic effects such as nausea. Continuous use might trigger adverse effects such as hyponatremia, tremor, nausea, weight gain, sleep disturbance and sexual dysfunction. Moderate toxicity can be safely observed in the hospital for 24 hours, and mild cases can be safely discharged (if asymptomatic) from the emergency department once cleared by Psychiatry in cases of intentional overdose and after 6 to 8 hours of observation. Although fluoxetine is relatively safe in terms of overdose, it might still be cardiotoxic and inhibit platelet secretion, aggregation, and plug formation. There have been reported clinical cases of seizures, cardiac conduction abnormalities, and even fatalities associated with fluoxetine ingestions. While the medical literature strongly suggests that most fluoxetine overdoses are benign, emergency physicians need to remain cognizant that intentional, high-dose fluoxetine ingestions may induce seizures and can even be fatal due to cardiac arrhythmia. Our case is a 35-year old female patient who was sent to ER with symptoms of confusion, amnesia and loss of orientation for time and location after being found wandering in the streets unconsciously by police forces that informed 112. Upon laboratory examination, no pathological symptom was found except sinus tachycardia in the EKG and high levels of aspartate transaminase (AST) and alanine transaminase (ALT). Diffusion MRI and computed tomography (CT) of the brain all looked normal. Upon physical and sexual examination, no signs of abuse or trauma were found. Test results for narcotics, stimulants and alcohol were negative as well. There was a presence of dysrhythmia which required admission to the intensive care unit (ICU). The patient gained back her conscience after 24 hours. It was discovered from her story afterward that she had been using fluoxetine due to post-traumatic stress disorder (PTSD) for 6 months and that she had attempted suicide after taking 3 boxes of fluoxetine due to the loss of a parent. She was then transferred to the psychiatric clinic. Our study aims to highlight the need to consider toxicologic drug use, in particular, the abuse of selective serotonin reuptake inhibitors (SSRIs), which have been widely prescribed due to presumed safety and tolerability, for diagnosis of patients applying to the emergency room (ER).

Keywords: abuse, amnesia, fluoxetine, intoxication, SSRI

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Authors: Werner Grommes

Abstract:

The institute of occupational safety and health works in a working group for building a normative standard for illuminated warning vests and did a lot of experiments and measurements as basic work (cooperation). Intelligent car headlamps are able to suppress conventional warning vests with retro-reflective stripes as a disturbing light. Illuminated warning vests are therefore required for occupational safety. However, they must not pose any danger to the wearer or other persons. Here, the risks of the batteries (lithium types), the maximum brightness (glare) and possible interference radiation from the electronics on the implant carrier must be taken into account. The all-around visibility, as well as the required range, play an important role here. For the study, many luminance measurements of already commercially available LEDs and electroluminescent warning vests, as well as their electromagnetic interference fields and aspects of electrical safety, were measured. The results of this study showed that LED lighting is all far too bright and causes strong glare. The integrated controls with pulse modulation and switching regulators cause electromagnetic interference fields. Rechargeable lithium batteries can explode depending on the temperature range. Electroluminescence brings even more hazards. A test method was developed for the evaluation of visibility at distances of 50, 100, and 150 m, including the interview of test persons. A measuring method was developed for the detection of glare effects at close range with the assignment of the maximum permissible luminance. The electromagnetic interference fields were tested in the time and frequency ranges. A risk and hazard analysis were prepared for the use of lithium batteries. The range of values for luminance and risk analysis for lithium batteries were discussed in the standards working group. These will be integrated into the standard. This paper gives a brief overview of the topics of illuminated warning vests, which takes into account the risks and hazards for the vest wearer or others

Keywords: illuminated warning vest, optical tests and measurements, risks, hazards, optical glare effects, LED, E-light, electric luminescent

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Authors: Nura Brimo, Dilek Cokeliler Serdaroglu, Tansel Uyar, Busra Uysal, Elif Bahar Cakici, Miris Dikmen, Zerrin Canturk

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Background: A combination of antibiotics, including metronidazole (MET), ciprofloxacin (CIP), and minocycline (MINO), has been demonstrated to disinfect bacteria in necrotic teeth before regenerative processes. It has been presented clinically that antibiotic pastes may drive to possible stem cell death and difficulties in removing from the canal system, which can limit the regenerative procedure. This study was designed to (1) synthesize nanofibrous webs containing various concentrations of different medicaments (triple, double, and calcium hydroxide,Ca(OH)2), and (2) coat thiselectrospun fibrous gutta-percha (GP) cones. Methods: Poly(vinylpyrrolidone) (PVP)-based electrospun fibrous webs were processed with low medicaments concentrations. Scanning Electron Microscopy (SEM), Energy Dispersive X-Ray Spectroscopy (EDX), and X-Ray Photoelectron Spectroscopy (XPS) were carried out to investigate fiber morphology, antibiotic incorporation, and characterized GP-coated fibrous webs, respectively. The chemical and physical properties of dentine were carried out via Fourier Transform Infrared Spectroscopy (FTIR) and Nano-SEM, respectively. The antimicrobial properties of the different fibrous webs were assessed against various bacteria by direct nanofiber/bacteria contact. Cytocompatibility was measured by applying the MTT method. Results: The mean fiber diameter of the experiment groups of medicament-containing fibers ranged in the nm scale and was significantly smaller than PVP fibers. EDX analysis confirmed the presence of medicaments in the nanofibers. XPS analysis presented a complete coating of the fibers with GPs; FTIR and Nano-SEM showed no chemical and physical configuration of intracanal medicaments on the dentine surface. Meanwhile, nanofibrous webs led to a significant reduction in the percentage of viable bacteria compared with the negative control and PVP. Conclusion: Our findings suggest that TA-NFs, DA-NFs, and Cₐ(OH)₂)-NFs coated GP cones have significant potential in eliminating intracanal bacteria, cell-friendly behavior, and clinical usage features.

Keywords: drug delivery, drug carrier, electrospinning, nano/microfibers, regenerative endodontic, morphology

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Authors: S. Roy, R. Rekha, K. Sriram, G. Subhadra, R. Johana

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Cardiovascular disease remains a leading cause of death in most industrialized countries. Many chemical drugs are available in the market which targets different receptor proteins related to cardiovascular diseases. Of late the traditional herbal drugs are safer when compared to chemical drugs because of its side effects. However, many herbal remedies used in treating cardiovascular diseases have not undergone scientific assessment to prove its pharmacological activities. There are many natural compounds, nature derived and Natural product mimic compounds are available which are in the market as approved drug. In the most of the cases drug activity at the molecular level are not known. Here we have categorized those compounds with our experimental compounds in different classes based on the structural similarity and physicochemical properties, using a tool, Chemmine and has attempted to understand the mechanism of the action of a experimental compound, which are clustered with Simvastatin, Lovastatin, Mevastatin and Pravastatin. Target protein molecule for Simvastatin, Lovastatin, Mevastatin and Pravastatin is HMG-CoA reductase, so we concluded that the experimental compound may be able to bind to the same target. Molecular docking and atomic interaction studies with simvastatin and our experimental compound were compared. A pharmacophore modeling was done based on the experimental compound and HMG-CoA reductase inhibitor.

Keywords: molecular docking, physicochemical properties, pharmacophore modeling structural similarity, pravastatin

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Authors: Hyeon-Kyo Lim, Tong-Il Jang, Yong-Hee Lee

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For an operator in a nuclear power plant, human error is one of the most dreaded factors that may result in unexpected accidents. The possibility of human errors may be low, but the risk of them would be unimaginably enormous. Thus, for accident prevention, it is quite indispensable to analyze the influence of any factors which may raise the possibility of human errors. During the past decades, not a few research results showed that performance of human operators may vary over time due to lots of factors. Among them, stress is known to be an indirect factor that may cause human errors and result in mental illness. Until now, not a few assessment tools have been developed to assess stress level of human workers. However, it still is questionable to utilize them for human performance anticipation which is related with human error possibility, because they were mainly developed from the viewpoint of mental health rather than industrial safety. Stress level of a person may go up or down with work time. In that sense, if they would be applicable in the safety aspect, they should be able to assess the variation resulted from work time at least. Therefore, this study aimed to compare their applicability for safety purpose. More than 10 kinds of work stress tools were analyzed with reference to assessment items, assessment and analysis methods, and follow-up measures which are known to close related factors with work stress. The results showed that most tools mainly focused their weights on some common organizational factors such as demands, supports, and relationships, in sequence. Their weights were broadly similar. However, they failed to recommend practical solutions. Instead, they merely advised to set up overall counterplans in PDCA cycle or risk management activities which would be far from practical human error prevention. Thus, it was concluded that application of stress assessment tools mainly developed for mental health seemed to be impractical for safety purpose with respect to human performance anticipation, and that development of a new assessment tools would be inevitable if anyone wants to assess stress level in the aspect of human performance variation and accident prevention. As a consequence, as practical counterplans, this study proposed a new scheme for assessment of work stress level of a human operator that may vary over work time which is closely related with the possibility of human errors.

Keywords: human error, human performance, work stress, assessment tool, time-variant, accident prevention

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Authors: Shogo Kato, Daisuke Okamoto, Satoko Tsuru, Yoshinori Iizuka, Ryoko Shimono

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Healthcare safety has been perceived important. It is essential to prevent troubles in healthcare processes for healthcare safety. Trouble prevention is based on trouble prediction using accumulated knowledge on processes, troubles, and countermeasures. However, information on troubles has not been accumulated in hospitals in the appropriate structure, and it has not been utilized effectively to prevent troubles. In the previous study, though a detailed knowledge acquisition process for trouble prediction was proposed, the knowledgebase for countermeasures was not involved. In this paper, we aim to propose the structure of the knowledgebase for countermeasures in the knowledge acquisition process for trouble prediction in healthcare process. We first design the structure of countermeasures and propose the knowledge representation form on countermeasures. Then, we evaluate the validity of the proposal, by applying it into an actual hospital.

Keywords: trouble prevention, knowledge structure, structured knowledge, reusable knowledge

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Authors: Yeganeh Jabbari, Sepideh Khalatabad

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This study explores the development of virtual reality (VR) technology for training applications, specifically its the potential benefits of VR technology for employee training and its ability to simulate real-world scenarios in a safe and controlled environment are highlighted, along with the associated cost and time savings. The adoption of VR technology in high-risk industrial organizations such as the oil and gas industry is discussed, with a focus on its ability to improve worker performance. Additionally, the use of VR technology in activities such as simulation and data visualization in the oil and gas industry is explored, leading to enhanced safety measures and collaboration between teams. The integration of advanced technologies such as robotics is mentioned as a way to further promote efficiency and sustainability. Also, the study mentions that the digital transformation of the oil and gas industry is revolutionizing operations and promoting safety, efficiency, and sustainability through the use of VR technology.

Keywords: virtual reality training, virtual reality benefits, high-risk industries, digital transformation

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Authors: Weiam Daear, Patrick Lai, Elmar Prenner

Abstract:

The human body offers many avenues that could be used for drug delivery. The pulmonary route, which is delivered through the lungs, presents many advantages that have sparked interested in the field. These advantages include; 1) direct access to the lungs and the large surface area it provides, and 2) close proximity to the blood circulation. The air-blood barrier of the alveoli is about 500 nm thick. The air-blood barrier consist of a monolayer of lipids and few proteins called the lung surfactant and cells. This monolayer consists of ~90% lipids and ~10% proteins that are produced by the alveolar epithelial cells. The two major lipid classes constitutes of various saturation and chain length of phosphatidylcholine (PC) and phosphatidylglycerol (PG) representing 80% of total lipid component. The major role of the lung surfactant monolayer is to reduce surface tension experienced during breathing cycles in order to prevent lung collapse. In terms of the pulmonary drug delivery route, drugs pass through various parts of the respiratory system before reaching the alveoli. It is at this location that the lung surfactant functions as the air-blood barrier for drugs. As the field of nanomedicine advances, the use of nanoparticles (NPs) as drug delivery vehicles is becoming very important. This is due to the advantages NPs provide with their large surface area and potential specific targeting. Therefore, studying the interaction of NPs with lung surfactant and whether they affect its stability becomes very essential. The aim of this research is to develop a biomimetic model of the human lung surfactant followed by a biophysical analysis of the interaction of polymeric NPs. This biomimetic model will function as a fast initial mode of testing for whether NPs affect the stability of the human lung surfactant. The model developed thus far is an 8-component lipid system that contains major PC and PG lipids. Recently, a custom made 16:0/16:1 PC and PG lipids were added to the model system. In the human lung surfactant, these lipids constitute 16% of the total lipid component. According to the author’s knowledge, there is not much monolayer data on the biophysical analysis of the 16:0/16:1 lipids, therefore more analysis will be discussed here. Biophysical techniques such as the Langmuir Trough is used for stability measurements which monitors changes to a monolayer's surface pressure upon NP interaction. Furthermore, Brewster Angle Microscopy (BAM) employed to visualize changes to the lateral domain organization. Results show preferential interactions of NPs with different lipid groups that is also dependent on the monolayer fluidity. Furthermore, results show that the film stability upon compression is unaffected, but there are significant changes in the lateral domain organization of the lung surfactant upon NP addition. This research is significant in the field of pulmonary drug delivery. It is shown that NPs within a certain size range are safe for the pulmonary route, but little is known about the mode of interaction of those polymeric NPs. Moreover, this work will provide additional information about the nanotoxicology of NPs tested.

Keywords: Brewster angle microscopy, lipids, lung surfactant, nanoparticles

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