Search results for: drug safety

Authors: Naser Kazemi Eilaki, Ilona Heldal, Carolyn Ahmer, Bjarne Christian Hagen

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Elderly people and people with disabilities are recognized as at-risk groups when it comes to egress and travel from hazard zone to a safe place. One's disability can negatively influence her or his escape time, and this becomes even more important when people from this target group live alone. While earlier studies have frequently addressed quantitative measurements regarding at-risk groups' physical characteristics (e.g., their speed of travel), this paper considers the influence of at-risk groups’ characteristics on their decision and determining better escape routes. Most of evacuation models are based on mapping people's movement and their behaviour to summation times for common activity types on a timeline. Usually, timeline models estimate required safe egress time (RSET) as a sum of four timespans: detection, alarm, premovement, and movement time, and compare this with the available safe egress time (ASET) to determine what is influencing the margin of safety.This paper presents a cross-sectional study for identifying the most critical items on RSET and people's decision-making and with possibilities to include safety knowledge regarding people with physical or cognitive functional impairments. The result will contribute to increased knowledge on considering at-risk groups and disabilities for designing and developing safe escape routes. The expected results can be an asset to predict the probabilistic behavioural pattern of at-risk groups and necessary components for defining a framework for understanding how stakeholders can consider various disabilities when determining the margin of safety for a safe escape route.

Keywords: fire safety, evacuation, decision-making, at-risk groups

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Authors: D. S. Gomes, A. T. Silva

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Analysis of the uncertainty quantification related to nuclear safety margins applied to the nuclear reactor is an important concept to prevent future radioactive accidents. The nuclear fuel performance code may involve the tolerance level determined by traditional deterministic models producing acceptable results at burn cycles under 62 GWd/MTU. The behavior of nuclear fuel can simulate applying a series of material properties under irradiation and physics models to calculate the safety limits. In this study, theoretical predictions of nuclear fuel failure under transient conditions investigate extended radiation cycles at 75 GWd/MTU, considering the behavior of fuel rods in light-water reactors under reactivity accident conditions. The fuel pellet can melt due to the quick increase of reactivity during a transient. Large power excursions in the reactor are the subject of interest bringing to a treatment that is known as the Fuchs-Hansen model. The point kinetic neutron equations show similar characteristics of non-linear differential equations. In this investigation, the multivariate logistic regression is employed to a probabilistic forecast of fuel failure. A comparison of computational simulation and experimental results was acceptable. The experiments carried out use the pre-irradiated fuels rods subjected to a rapid energy pulse which exhibits the same behavior during a nuclear accident. The propagation of uncertainty utilizes the Wilk's formulation. The variables chosen as essential to failure prediction were the fuel burnup, the applied peak power, the pulse width, the oxidation layer thickness, and the cladding type.

Keywords: logistic regression, reactivity-initiated accident, safety margins, uncertainty propagation

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Authors: Inna Kornienko, Svetlana Guryeva, Natalia Danilova, Elena Petersen

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Drug toxicity often goes undetected until clinical trials, the most expensive and dangerous phase of drug development. Both human cell culture and animal studies have limitations that cannot be overcome by improvements in drug testing protocols. Tissue engineering is an emerging alternative approach to creating models of human malignant tumors for experimental oncology, personalized medicine, and drug discovery studies. This new generation of bioengineered tumors provides an opportunity to control and explore the role of every component of the model system including cell populations, supportive scaffolds, and signaling molecules. An area that could greatly benefit from these models is cancer research. Recent advances in tissue engineering demonstrated that decellularized tissue is an excellent scaffold for tissue engineering. Decellularization of donor organs such as heart, liver, and lung can provide an acellular, naturally occurring three-dimensional biologic scaffold material that can then be seeded with selected cell populations. Preliminary studies in animal models have provided encouraging results for the proof of concept. Decellularized Organs preserve organ microenvironment, which is critical for cancer metastasis. Utilizing 3D tumor models results greater proximity of cell culture morphological characteristics in a model to its in vivo counterpart, allows more accurate simulation of the processes within a functioning tumor and its pathogenesis. 3D models allow study of migration processes and cell proliferation with higher reliability as well. Moreover, cancer cells in a 3D model bear closer resemblance to living conditions in terms of gene expression, cell surface receptor expression, and signaling. 2D cell monolayers do not provide the geometrical and mechanical cues of tissues in vivo and are, therefore, not suitable to accurately predict the responses of living organisms. 3D models can provide several levels of complexity from simple monocultures of cancer cell lines in liquid environment comprised of oxygen and nutrient gradients and cell-cell interaction to more advanced models, which include co-culturing with other cell types, such as endothelial and immune cells. Following this reasoning, spheroids cultivated from one or multiple patient-derived cell lines can be utilized to seed the matrix rather than monolayer cells. This approach furthers the progress towards personalized medicine. As an initial step to create a new ex vivo tissue engineered model of a cancer tumor, optimized protocols have been designed to obtain organ-specific acellular matrices and evaluate their potential as tissue engineered scaffolds for cultures of normal and tumor cells. Decellularized biomatrix was prepared from animals’ kidneys, urethra, lungs, heart, and liver by two decellularization methods: perfusion in a bioreactor system and immersion-agitation on an orbital shaker with the use of various detergents (SDS, Triton X-100) in different concentrations and freezing. Acellular scaffolds and tissue engineered constructs have been characterized and compared using morphological methods. Models using decellularized matrix have certain advantages, such as maintaining native extracellular matrix properties and biomimetic microenvironment for cancer cells; compatibility with multiple cell types for cell culture and drug screening; utilization to culture patient-derived cells in vitro to evaluate different anticancer therapeutics for developing personalized medicines.

Keywords: 3D models, decellularization, drug discovery, drug toxicity, scaffolds, spheroids, tissue engineering

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Authors: Amira M. Hassanein, Nehal A. Salahuddin, Atsunori Matsuda, Toshiaki Hattori, Mona N. Elfiky

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New insights into the design of highly sensitive, carbon-based electrochemical sensors are presented in this work. This was achieved by exploring the interesting properties of conductive (Mg/Al) layered double hydroxide- Dodecyl Sulphate/Polypyrrole nanocomposites which were synthesized by in-situ polymerization of pyrrole during the assembly of (Mg/Al) layered double hydroxide, and by employing the anionic surfactant Dodecyl sulphate as a modifier. The morphology and surface area of the nanocomposites changed with the percentage of Pyrrole. Under optimal conditions, the modified carbon paste electrode successfully achieved detection limits of 0.057 and 0.134 nmol.L-1 of Terazosin hydrochloride in pharmaceutical formulation and spiked human serum fluid, respectively. Moreover, the sensors are highly stable, reusable, and free from interference by other commonly present excipients in drug formulations.

Keywords: layered double hydroxide, polypyrrole, terazosin hydrochloride, square-wave adsorptive anodic stripping voltammetry

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Authors: Tresna Lestari, Tita Nofianti, Ade Yeni Aprilia, Lilis Tuslinah, Ruswanto Ruswanto

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Nanoparticle formulation is often used to improve drug absorptivity, thus increasing the sharpness of the action. Ginger torch flower extract was formulated into nanoparticle form using poloxamer 1, 3 and 5%. The nanoparticle was then characterized by its particle size, polydispersity index, zeta potential, entrapment efficiency and morphological form by SEM. The result shows that nanoparticle formulations have particle size 134.7-193.1 nm, polydispersity index less than 0.5 for all formulations, zeta potential -41.0 - (-24.3) mV and entrapment efficiency 89.93-97.99 against flavonoid content with a soft surface and spherical form of particles. Methanolic extract of ginger torch flower could enhance superoxide dismutase activity by 1,3183 U/mL in male rats. Nanoparticle formulation of ginger torch extract is expected to increase the capability of the drug to enhance superoxide dismutase activity.

Keywords: superoxide dismutase, ginger torch flower, nanoparticle, poloxamer

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Authors: Mohammed Ghazwani, Shyma Ali Alshahrani, Zahra Abdu Yousef, Taif Torki Asiri, Ghofran Abdur Rahman, Asma Ali Alshahrani, Umme Hani

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Background and introduction: Piroxicam is a nonsteroidal anti-inflammatory drug characterized by low solubility-high permeability used to reduce pain, swelling, and joint stiffness from arthritis. Hydrotropes are a class of compounds that normally increase the aqueous solubility of insoluble solutes. Aim: The objective of the present research study was to formulate and optimize Piroxicam hydrotropic starch gel using sodium salicylate, sodium benzoate as hydrotropic salts, and potato starch for topical application. Materials and methods: The prepared Piroxicam hydrotropic starch gel was characterized for various physicochemical parameters like drug content estimation, pH, tube extrudability, and spreadability; all the prepared formulations were subjected to in-vitro diffusion studies for six hours in 100 ml phosphate buffer (pH 7.4) and determined gel strength. Results: All formulations were found to be white opaque in appearance and have good homogeneity. The pH of formulations was found to be between 6.9-7.9. Drug content ranged from 96.8%-99.4.5%. Spreadability plays an important role in patient compliance and helps in the uniform application of gel to the skin as gels should spread easily; F4 showed a spreadability of 2.4cm highest among all other formulations. In in vitro diffusion studies, extrudability and gel strength were good with F4 in comparison with other formulations; hence F4 was selected as the optimized formulation. Conclusion: Isolated potato starch was successfully employed to prepare the gel. Hydrotropic salt sodium salicylate increased the solubility of Piroxicam and resulted in a stable gel, whereas the gel prepared using sodium benzoate changed its color after one week of preparation from white to light yellowish. Hydrotropic potato starch gel proposed a suitable vehicle for the topical delivery of Piroxicam.

Keywords: Piroxicam, potato starch, hydrotropic salts, hydrotropic starch gel

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Authors: Lo Kar Yin

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In view of the increasing speed and quantity of the housing supply, building, and civil engineering infrastructure works triggered by the pandemic across the globe, contractors, professional services providers (PSP), including consultants (e.g., architect, project manager, civil/geotechnical/structural engineer, building services engineer, quantity surveyor/cost manager, etc.) and suppliers have faced tremendous challenges of the fierce market, limited manpower, and resources under contract prices fluctuation and competitive fee and price. With qualitative analysis, this paper is to review the available information from the industry stakeholders with a view to finding solutions for enhancing efficiency, safety, and quality of construction value chain services for public and private organizations/companies’ sustainable growth, not limited to checking the deliverables and data transfer from multi-disciplinary parties. Technology, contracts, and people are the key requirements for shaping the construction industry. With the integration of a modern engineering contract (e.g., NEC) collaborative approach, practical workflows are designed to address loopholes together with different levels of people employment/retention and technology adoption to achieve the best value for money.

Keywords: efficiency, safety, quality, technology, contract, people, sustainable solutions, construction, services, integration

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Authors: Tuji Jemal Ahmed, Abdi Mohammed, Geremew Geidare Kailo

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Food security, foodborne illness, and food safety are critical issues that affect the East Harerghe region of Oromia, Ethiopia. Despite the region's potential for agriculture, food insecurity remains a significant problem, with many households experiencing chronic hunger and malnutrition. The region also experiences high rates of foodborne illnesses, including cholera, typhoid, and diarrhea, which are caused by poor hygiene and sanitation practices. Additionally, food safety is a significant challenge, particularly in rural areas, where there is a lack of infrastructure, inadequate food storage facilities, and limited access to information about food safety. There are several factors that contribute to the current situation in the East Harerghe region; firstly, the region is susceptible to natural disasters, for instance, drought, which affects crop yields and livestock production. Secondly, the region also experiences poor infrastructure, which affects the storage and transportation of food, particularly in rural areas. Thirdly, there is a lack of awareness and knowledge on good hygiene and sanitation practices, specifically during food handling, processing, and storage. Fourthly, unitability due to conflict and other forms of land degradation exacerbates food insecurity and malnutrition. Finally, limited access to financial resources and markets commonly affects smallholder farmers by their ability to produce and sell food. To address the current situation in that area, several potential solutions can be implemented; investment in infrastructure is necessary, especially in rural areas, to improve the storage and transportation of food. Education and awareness programs on good hygiene and sanitation practices should target local communities, smallholder farmers, and food vendors. Financial resources and markets should be made more accessible to smallholder farmers, particularly through the provision of credit and improved access to markets. Addressing the underlying causes of conflict and promoting peaceful coexistence can help to reduce displacement and loss of livelihoods. Finally, the enforcement of food safety regulations and the implementation of standards for food processing and storage facilities are necessary to ensure food safety. In conclusion, addressing the challenges of food security, foodborne illness, and food safety in the East Harerghe region requires a coordinated effort from various stakeholders, including the government, non-governmental organizations, and local communities. By implementing the solutions outlined above, the region can improve its food security, prevent foodborne illnesses, and keep food safe for its population. Eventually, building the resilience of communities to shocks such as droughts, floods, and conflict is necessary to ensure long-term food security in the region.

Keywords: foodborne illness, food handling, food safety, food security

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Authors: Viriyavudh Sim, WooYoung Jung

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Window system in high rise building is occasionally subjected to an excessive wind intensity, particularly during typhoon. The failure of window system did not affect overall safety of structural performance; however, it could endanger the safety of the residents. In this paper, comparison of fragility curves for window system of two residential buildings was studied. The probability of failure for individual window was determined with Monte Carlo Simulation method. Then, lognormal cumulative distribution function was used to represent the fragility. The results showed that windows located on the edge of leeward wall were more susceptible to wind load and the probability of failure for each window panel increased at higher floors.

Keywords: wind fragility, window system, high rise building, wind disaster

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Authors: Olawole Emmanuel Aina, Liziwe Lizbeth Mugivhisa, Joshua Oluwole Olowoyo, Chikwela Lawrence Obi

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In sustained and consistent efforts to improve food security, numerous and different methods are proposed and used in the production of food crops, and farm produce to meet the demands of consumers. However, unregulated and indiscriminate methods of production present another problem that may expose consumers of these food crops to potential health risks. Therefore, it is imperative that a thorough assessment of farm produce is carried out due to the growing trend of health-conscious consumers preference for minimally processed or raw farm produce. This study evaluated the safety and nutritional quality of food crops. The objectives were to compare the nutritional quality of organic and inorganic farm produce in one hand and, on the other, evaluate the safety of farm produce with respect to trace metal and pathogenic contamination. We conducted a broad systematic search of peer-reviewed published literatures from databases and search engines such as science direct, web-of-science, Google scholar, and Scopus. This study concluded that there is no conclusive evidence to support the notion of nutritional superiority of organic food crops over their inorganic counterparts and there are documented reports of pathogenic and metal contaminations of food crops.

Keywords: food crops, fruits and vegetables, pathogens, nutrition, trace metals

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Authors: Kyungsuk Cho, H. Y. Kim, S. U. Chae, J. H. Choi

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Technological development has led to the construction of super-tall buildings and insulators are increasingly used as exterior finishing materials to save energy. However, insulators are usually combustible and vulnerable to fire. Fires like that at Wooshin Golden Suite Building in Busan, Korea in 2010 and that at CCTV Building in Beijing, China are the major examples of fire spread accelerated by combustible insulators. The exterior finishing materials of a high-rise building are not made of insulators only, but they are integrated with the building’s external cladding system. There is a limit in evaluating the fire safety of a cladding system with a single small-unit material such as a cone calorimeter. Therefore, countries provide codes to evaluate the fire safety of exterior finishing materials using full-scale tests. This study compares and to examine the applicability of the methods to Korea. Standard analysis showed differences in the type and size of fire sources and duration and exterior finishing materials also differed in size. In order to confirm the differences, fire tests were conducted on identical external cladding systems to compare fire safety. Although the exterior finishing materials were identical, varying degrees of fire spread were observed, which could be considered as differences in the type and size of the fire sources and duration. Therefore, it is deduced that extended studies should be conducted before the evaluation methods and standards are employed in Korea. The two standards for evaluating fire safety provided different results. Peak heat release rate was 5.5MW in ISO method and 3.0±0.5MW in BS method. Peak heat release rate in ISO method continued for 15 minutes. Fire ignition, growth, full development and decay evolved for 30 minutes in BS method where wood cribs were used as fire sources. Therefore, follow-up studies should be conducted to determine which of the two standards provides fire sources that approximate the size of flames coming out from the openings or those spreading to the outside when a fire occurs at a high-rise building.

Keywords: external cladding systems, fire safety evaluation, ISO 13785-2, BS 8414

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Authors: Sunil Kamboj, Vipin Saini, Suman Bala, Gaurav Sharma

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The main aim of the present research was to encapsulate mefenamic acid in niosomes and incorporate the prepared niosomes in the carbopol gel base for sustained therapeutic action. Mefenamic acid loaded niosomes were prepared by thin film hydration technique and evaluated for entrapment efficiency, vesicular size and zeta potential. The entrapment efficiency of the prepared niosomes was found to increase with decreasing the HLB values of surfactants and vesicle size was found to increase with increasing the cholesterol concentration. Niosomal vesicles with good entrapment efficiencies were incorporated in carbopol gel base to form the niosomal gel. The prepared niosomal gel was evaluated for pH, viscosity, spreadability, extrudability and skin permeation study across the rat skin.The results of permeation study revealed that the gel formulated with span 60 niosomes sustained the drug release for 12 h. Further the in vivo study showed the good inhibition of inflammation by the gel prepared with span 60 niosomes.

Keywords: mefenamic acid, niosomal gel, nonionic surfactants, sustained release

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Authors: Y. Chiang, J. R. Wang, J. H. Yang, Y. S. Tseng, C. Shih, S. W. Chen

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Kuosheng nuclear power plant (NPP) is a BWR/6 plant in Taiwan. There is more concern for the safety of Spent Fuel Pools (SFPs) in Taiwan after Fukushima event. In order to estimate the safety of Kuosheng NPP SFP, by using MELCOR2.1 and SNAP, the safety analysis of Kuosheng NPP SFP was performed combined with the mitigation strategy of NEI 06-12 report. There were several steps in this research. First, the Kuosheng NPP SFP models were established by MELCOR2.1/SNAP. Second, the Station Blackout (SBO) analysis of Kuosheng SFP was done by TRACE and MELCOR under the cooling system failure condition. The results showed that the calculations of MELCOR and TRACE were very similar in this case. Second, the mitigation strategy analysis was done with the MELCOR model by following the NEI 06-12 report. The results showed the effectiveness of NEI 06-12 strategy in Kuosheng NPP SFP. Finally, a sensitivity study of SFP quenching was done to check the differences of different water injection time and the phenomena during the quenching. The results showed that if the cladding temperature was over 1600 K, the water injection may have chance to cause the accident more severe with more hydrogen generation. It was because of the oxidation heat and the “Breakaway” effect of the zirconium-water reaction. An animation model built by SNAP was also shown in this study.

Keywords: MELCOR, SNAP, spent fuel pool, quenching

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Authors: Richard J. Hanowski, Rebecca L. Hammond

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Very few studies have been conducted to investigate safety issues associated with motorcoach/bus operations. The current study investigates the impact that roadway infrastructure, including locality, roadway grade, traffic flow and traffic density, have on bus safety. A naturalistic driving study was conducted in the U.S.A that involved 43 motorcoaches. Two fleets participated in the study and over 600,000 miles of naturalistic driving data were collected. Sixty-five bus drivers participated in this study; 48 male and 17 female. The average age of the drivers was 49 years. A sophisticated data acquisition system (DAS) was installed on each of the 43 motorcoaches and a variety of kinematic and video data were continuously recorded. The data were analyzed by identifying safety critical events (SCEs), which included crashes, near-crashes, crash-relevant conflicts, and unintentional lane deviations. Additionally, baseline (normative driving) segments were also identified and analyzed for comparison to the SCEs. This presentation highlights the need for bus safety research and the methods used in this data collection effort. With respect to elements of roadway infrastructure, this study highlights the methods used to assess locality, roadway grade, traffic flow, and traffic density. Locality was determined by manual review of the recorded video for each event and baseline and was characterized in terms of open country, residential, business/industrial, church, playground, school, urban, airport, interstate, and other. Roadway grade was similarly determined through video review and characterized in terms of level, grade up, grade down, hillcrest, and dip. The video was also used to make a determination of the traffic flow and traffic density at the time of the event or baseline segment. For traffic flow, video was used to assess which of the following best characterized the event or baseline: not divided (2-way traffic), not divided (center 2-way left turn lane), divided (median or barrier), one-way traffic, or no lanes. In terms of traffic density, level-of-service categories were used: A1, A2, B, C, D, E, and F. Highlighted in this abstract are only a few of the many roadway elements that were coded in this study. Other elements included lighting levels, weather conditions, roadway surface conditions, relation to junction, and roadway alignment. Note that a key component of this study was to assess the impact that driver distraction and fatigue have on bus operations. In this regard, once the roadway elements had been coded, the primary research questions that were addressed were (i) “What environmental condition are associated with driver choice of engagement in tasks?”, and (ii) “what are the odds of being in a SCE while engaging in tasks while encountering these conditions?”. The study may be of interest to researchers and traffic engineers that are interested in the relationship between roadway infrastructure elements and safety events in motorcoach bus operations.

Keywords: bus safety, motorcoach, naturalistic driving, roadway infrastructure

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Authors: Dmitry Nosik, Nickolay Nosik, Elli Kaplina, Olga Lobach, Marina Chataeva, Lev Rasnetsov

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Background and aims: Human Immunodeficiency Virus (HIV) infection is very often associated with Herpes Simplex Virus (HSV) infection but HIV patients are treated with a cocktail of antiretroviral drugs which are toxic. The use of an antiviral drug which will be active against both viruses like ferrovir found in our previous studies is rather actual. Earlier we had shown that Fullerene poly-amino capronic acid (FPACA) was active in case of monoinfection of HIV-1 or HSV-1. The aim of the study was to analyze the efficiency of FPACA against mixed infection of HIV and HSV. Methods: The peripheral blood lymphocytes, CEM, MT-4 cells were simultaneously infected with HIV-1 and HSV-1. FPACA was added 1 hour before infection. Cells viability was detected by MTT assay, virus antigens detected by ELISA, syncytium formation detected by microscopy. The different multiplicity of HIV-1/HSV-1 ratio was used. Results: The double viral HIV-1/HSV-1 infection was more cytopathic comparing with monoinfections. In mixed infection by the HIV-1/HSV-1 concentration of HIV-1 antigens and syncytium formations increased by 1,7 to 2,3 times in different cells in comparison with the culture infected with HIV-1 alone. The concentration of HSV-1 increased by 1,5-1,7 times, respectively. Administration of FPACA (1 microg/ml) protected cells: HIV-1/HSV-1 (1:1) – 80,1%; HIV-1/HSV-1 (1:4) – 57,2%; HIV-1/HSV-1 (1:8) – 46,3 %; HIV-1/HSV-1 (1:16) – 17,0%. Virus’s antigen levels were also reduced. Syncytium formation was totally inhibited in all cases of mixed infection. Conclusion: FPACA showed antiviral activity in case of mixed viral infection induced by Human Immunodeficiency Virus and Herpes Simplex Virus. The effect of viral inhibition increased with the multiplicity of HIV-1 in the inoculum. The mechanism of FPACA action is connected with the blocking of the virus particles adsorption to the cells and it could be suggested that it can have an antiviral activity against some other viruses too. Now FPACA could be considered as a potential drug for treatment of HIV disease complicated with opportunistic herpes viral infection.

Keywords: antiviral drug, human immunodeficiency virus (hiv), herpes simplex virus (hsv), mixed viral infection

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Authors: Buhari Samaila, Buhari Maidamma

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Background: The use of ionizing radiation in medical diagnostics and treatment is indispensable for accurate imaging and effective cancer therapies. However, radiation exposure carries inherent risks, necessitating strict protection measures to safeguard both patients and healthcare workers. This review critically examines the existing radiation protection measures in diagnostic radiology and radiotherapy, highlighting technological advancements, regulatory frameworks, and challenges. Objective: The objective of this review is to critically evaluate the effectiveness of current radiation protection measures in diagnostic and therapeutic radiology, focusing on minimizing patient and staff exposure to ionizing radiation while ensuring optimal clinical outcomes and propose future directions for improvement. Method: A comprehensive literature review was conducted, covering scientific studies, regulatory guidelines, and international standards on radiation protection in both diagnostic radiology and radiotherapy. Emphasis was placed on ALARA principles, dose optimization techniques, and protective measures for both patients and healthcare workers. Results: Radiation protection measures in diagnostic radiology include the use of shielding devices, minimizing exposure times, and employing advanced imaging technologies to reduce dose. In radiotherapy, accurate treatment planning and image-guided techniques enhance patient safety, while shielding and dose monitoring safeguard healthcare personnel. Challenges such as limited infrastructure in low-income settings and gaps in healthcare worker training persist, impacting the overall efficacy of protection strategies. Conclusion: While significant advancements have been made in radiation protection, challenges remain in optimizing safety, especially in resource-limited settings. Future efforts should focus on enhancing training, investing in advanced technologies, and strengthening regulatory compliance to ensure continuous improvement in radiation safety practices.

Keywords: radiation protection, diagnostic radiology, radiotherapy, ALARA, patient safety, healthcare worker safety

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Authors: Rania Awad, Avi Avital, Alejandro Sosnik

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Neurodevelopmental disorders, including autism spectrum disorder (ASD), affect 5.9% of the global population. Recently, research indicated the potential therapeutic use of cannabidiol (CBD) to treat different neurodevelopmental disorders, including ASD. Intranasal drug delivery (IN) is a non-invasive and painless administration route that enhances drug bioavailability in the brain by bypassing the blood-brain barrier. However, IN has limited bioavailability due to the low nasal mucosa permeability. Various polymeric nanoparticles (NPs) have been investigated for IN delivery with different successes. In this study, we investigate the nanoencapsulation of CBD within self-assembled polymeric NPs for nose-to-brain delivery in ASD to increase the bioavailability of CBD in the brain. The nanoencapsulation of CBD within self-assembled polymeric NPs, namely poly (ethylene oxide)-b-poly (propylene oxide)-b-poly (ethylene oxide) (PEO-PPO-PEO) polymeric micelles, was assessed. The CBD-loaded system was characterized by different methods. The compatibility was assessed in the nasal septum epithelium cell line Rpmi 2650. In vitro, permeability studies were conducted using Rpmi2650 cell monolayers cultured in semipermeable membranes 2650. The accumulation of CBD-loaded NPs labeled with near-infra-red fluorescent dye in the brain was measured after IN and oral administration after 20 and 45 min using IVIS spectrum CT imaging (IVIS-CT). Pharmacokinetic (PK) studies were conducted to assess the CBD concentration in rat plasma and brain tissues at different time points, PK parameters were measured and analyzed. Then, the effect of IN and oral administration of CBD-loaded NPs on a social cooperation test, which is a relevant behavioral test in the ASD model in rats, was investigated. Initially, we produced Pluronic® F127 polymeric micelles loaded with 25% w/w of CBD, with a size of 23 ± 1 nm, with suitable physical properties for IN administration. Then, Pluronic® F127 nanoparticles (F127 NPs) in the medium showed good compatibility and permeability in Rpmi 2650 cells. In the IVIS-CT study, the accumulation of IN administration of CBD-loaded F127 in the rat's brains was higher than the oral. Pharmacokinetic analysis of rat brain tissues revealed that, 20 minutes after administration, the concentration of CBD was higher following a 5 mg/kg nasal administration compared to a 15 mg/kg oral administration of CBD-loaded F127. Followed by IN administration of CBD-loaded F127 improved the social cooperation performance of the ASD model in rats as compared to oral and control groups.

Keywords: drug delivery to the brain, Intranasal drug delivery, nanoencapsulation, neurodevelopmental disorders, polymeric nanoparticles.

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Authors: M. Chen, S-Q. Zhang, X. Wang, D. Tate

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This paper presents a numerical solution, namely limit and shakedown analysis, to predict the safety state of smart structures made of heterogeneous materials under unknown cyclic loadings, for instance, the flexure hinge in the micro-positioning stage driven by piezoelectric actuator. In combination of homogenization theory and finite-element method (FEM), the safety evaluation problem is converted to a large-scale nonlinear optimization programming for an acceptable bounded loading as the design reference. Furthermore, a general numerical scheme integrated with the FEM and interior-point-algorithm based optimization tool is developed, which makes the practical application possible.

Keywords: limit state, shakedown analysis, homogenization, heterogeneous structure

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Authors: Andrew Cummings, Rhianne Boag, Sarah Bryson, Gordon Turner

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Packages designed for transport of radioactive material must satisfy rigorous safety regulations specified by the International Atomic Energy Agency (IAEA). Higher Activity Waste (HAW) transport packages have to maintain containment of their contents during normal and accident conditions of transport (NCT and ACT). To ensure containment criteria is satisfied these packages are required to be leak-tight in all transport conditions to meet allowable activity release rates. Package design safety reports are the safety cases that provide the claims, evidence and arguments to demonstrate that packages meet the regulations and once approved by the competent authority (in the UK this is the Office for Nuclear Regulation) a licence to transport radioactive material is issued for the package(s). The standard approach to demonstrating containment in the RWM transport safety case is set out in BS EN ISO 12807. In this document a method for measuring a leak rate from the package is explained by way of a small interspace test volume situated between two O-ring seals on the underside of the package lid. The interspace volume is pressurised and a pressure drop measured. A small interspace test volume makes the method more sensitive enabling the measurement of smaller leak rates. By ascertaining the activity of the contents, identifying a releasable fraction of material and by treating that fraction of material as a gas, allowable leak rates for NCT and ACT are calculated. The adherence to basic safety principles in ISO12807 is very pessimistic and current practice in the demonstration of transport safety, which is accepted by the UK regulator. It is UK government policy that management of HAW will be through geological disposal. It is proposed that the intermediate level waste be transported to the geological disposal facility (GDF) in large cuboid packages. This poses a challenge for containment demonstration because such packages will have long seals and therefore large interspace test volumes. There is also uncertainty on the releasable fraction of material within the package ullage space. This is because the waste may be in many different forms which makes it difficult to define the fraction of material released by the waste package. Additionally because of the large interspace test volume, measuring the calculated leak rates may not be achievable. For this reason a justification for a lower releasable fraction of material is sought. This paper considers the use of aerosol processes to reduce the releasable fraction for both NCT and ACT. It reviews the basic coagulation and removal processes and applies the dynamic aerosol balance equation. The proposed solution includes only the most well understood physical processes namely; Brownian coagulation and gravitational settling. Other processes have been eliminated either on the basis that they would serve to reduce the release to the environment further (pessimistically in keeping with the essence of nuclear transport safety cases) or that they are not credible in the conditions of transport considered.

Keywords: aerosol processes, Brownian coagulation, gravitational settling, transport regulations

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Authors: Maz Muradvich

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The Federal Highway Administration's Everyday Counts (EDC) initiative is designed to identify and deploy innovations, enhancing the safety of our roadways. According to and as referenced in FHWA everyday counts (2) website, High friction surface treatment (HFST) is an emerging surface application that has been proven to reduce crashes. High Friction Surface Treatment involves the application of Calcined Bauxite, very high-quality aggregate to the pavement using a polymer binder to restore and maintain pavement friction at existing or potentially high crash areas. Bauxite is a byproduct of manufacturing aluminum resulting in very hard aggregate and is abrasion and polish resistant. HFST is an approach that has been recognized nationally and internationally and has provided considerable increases in friction for curves and intersections spot applications. Maricopa County qualified and received HSIP (Highway Safety Improvement Program) funding that was applied towards HFST application on 2 locations in Maricopa County. The project was successfully completed in December 2019. Four years later MCDOT continues to conduct wet and dry ABS and Non-ABS friction coefficient testing in pursuit of after studies evaluation of HFST application.

Keywords: roadway departure, sever crashes, coefficient of friction, break meter technology

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Authors: Muhammad Jawad Hashmi

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The idea of nuclear terrorism is as old as nuclear weapons but the global concerns of likelihood of nuclear terrorism are uncertain. Post 9/11 trends manifest that terrorists are believers of massive causalities. Innovation in terrorist’s tactics, sophisticated weaponry, vulnerability, theft and smuggling of nuclear/radiological material, connections between terrorists, black market and rough regimes are signaling seriousness of upcoming challenges as well as global trends of “terror-transnationalism.” Furthermore, the International-Atomic-Energy-Agency’s database recorded 2734 incidents regarding misuse, unauthorized possession, trafficking of nuclear material etc. Since, this data also includes incidents from south Asia, so, there is every possibility to claim that such illicit activities may increase in future, mainly due to expansion of nuclear industry in South Asia. Moreover, due to such mishaps the region is vulnerable to threats of nuclear terrorism. This is also a reason that the region is in limelight along with issues such as rapidly growing nuclear arsenals, nuclear safety and security, terrorism and political instability. With this backdrop, this study is aimed to investigate the prevailing threats and challenges in South Asia vis a vis nuclear safety and security. A comparative analysis of the overall capabilities would be done to identify the areas of cooperation to eliminate the probability of nuclear/radiological terrorism in the region.

Keywords: nuclear terrorism, safety, security, South Asia, india, Pakistan

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Authors: Jyoti Singh, Ranju Bansal

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Fighting pain and inflammation is a common problem faced by physicians while dealing with a wide variety of diseases. Since ancient time nonsteroidal anti-inflammatory agents (NSAIDs) and opioids have been the cornerstone of treatment therapy, however, the usefulness of both these classes is limited due to severe side effects. NSAIDs, which are mainly used to treat mild to moderate inflammatory pain, induce gastric irritation and nephrotoxicity whereas opioids show an array of adverse reactions such as respiratory depression, sedation, and constipation. Moreover, repeated administration of these drugs induces tolerance to the analgesic effects and physical dependence. Further discovery of selective COX-2 inhibitors (coxibs) suggested safety without any ulcerogenic side effects; however, long-term use of these drugs resulted in kidney and hepatic toxicity along with an increased risk of secondary cardiovascular effects. The basic approaches towards inflammation and pain treatment are constantly changing, and researchers are continuously trying to develop safer and effective anti-inflammatory drug candidates for the treatment of different inflammatory conditions such as osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, psoriasis and multiple sclerosis. Synthetic 3(2H)-pyridazinones constitute an important scaffold for drug discovery. Structure-activity relationship studies on pyridazinones have shown that attachment of a lactam at N-2 of the pyridazinone ring through a methylene spacer results in significantly increased anti-inflammatory and analgesic properties of the derivatives. Further introduction of the heterocyclic ring at lactam nitrogen results in improvement of biological activities. Keeping in mind these SAR studies, a new series of compounds were synthesized as shown in scheme 1 and investigated for anti-inflammatory, analgesic, anti-platelet activities and docking studies. The structures of newly synthesized compounds have been established by various spectroscopic techniques. All the synthesized pyridazinone derivatives exhibited potent anti-inflammatory and analgesic activity. Homoveratryl substituted derivative was found to possess highest anti-inflammatory and analgesic activity displaying 73.60 % inhibition of edema at 40 mg/kg with no ulcerogenic activity when compared to standard drugs indomethacin. Moreover, 2-substituted-4-benzo[d][1,3]dioxole-6-phenylpyridazin-3(2H)-ones derivatives did not produce significant changes in bleeding time and emerged as safe agents. Molecular docking studies also illustrated good binding interactions at the active site of the cyclooxygenase-2 (hCox-2) enzyme.

Keywords: anti-inflammatory, analgesic, pyridazin-3(2H)-one, selective COX-2 inhibitors

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Authors: Sekou Kangoye, Alexis Todoskoff, Mihaela Barreau

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Modified Condition/Decision Coverage (MC/DC) is a structural coverage criterion that is highly recommended or required for safety-critical software coverage. Therefore, many testing standards include this criterion and require it to be satisfied at a particular level of testing (e.g. validation and unit levels). However, an important amount of time is needed to meet those requirements. In this paper we propose to automate MC/DC test data generation. Thus, we present an approach to automatically generate MC/DC test data, from software module description written over a dedicated language. We introduce a new merging approach that provides high MC/DC coverage for the description, with only a little number of test cases.

Keywords: domain-specific language, MC/DC, test data generation, safety-critical software coverage

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Authors: Yulinda Rizky Pratiwi, Fuji Anugrah Emily

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Management of Occupational Safety and Health (OSH) are appropriately applied properly by all workers and pekarya in the company. K3 management application also has become very important to prevent accidents. Violation of the rules regarding the K3 has often occurred from time to time. By 2015 the number of occurrences of a violation of the K3 or so-called unsafe action tends to increase. Until finally in January 2016, the number increased drastically unsafe action. Trigger increase in the number of unsafe action is a decrease in the quality of management practices K3. While the application of K3 management performed by each individual thought to be influenced by the attitude and observation guide the actions of each of the individual. In addition to the decline in the quality of K3 management application may result in increased likelihood of accidents and losses for the company as well as the local co-workers. The big difference in the number of unsafe action is very significant in the month of January 2016, making the company Pertamina as the national oil company must do a lot of effort to keep track of how the implementation of K3 management on every worker and pekarya, one at PT Pertamina EP Cepu Field Asset IV. To consider the effort to control the implementation of K3 management can be seen from the attitude and observation guide the actions of the workers and pekarya. By using Multiple Linear Regression can be seen the influence of attitude and action observation guide workers and pekarya the K3 management application that has been done. The results showed that scores K3 management application of each worker and pekarya will increase by 0.764 if the score pekarya worker attitudes and increase one unit, whereas if the score Reassurance action guidelines and pekarya workers increased by one unit then the score management application K3 will increase by 0.754.

Keywords: occupational safety and health, management of occupational safety and health, unsafe action, multiple linear regression

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Authors: Huseyin Sinan Gunesli

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Process Safety Management is a disciplined framework for managing the integrity of systems and processes that handle hazardous substances. It relies on good design principles, well-implemented automation systems, and operating and maintenance practices. Alarm Management Systems play a critically important role in the safe and efficient operation of modern industrial plants. In that respect, Alarm Management is one of the critical factors feeding the safe operations of the plants in the manner of applying effective process safety principles. Trans Anatolian Natural Gas Pipeline (TANAP) is part of the Southern Gas Corridor, which extends from the Caspian Sea to Italy. TANAP transports Natural Gas from the Shah Deniz gas field of Azerbaijan, and possibly from other neighboring countries, to Turkey and through Trans Adriatic Pipeline (TAP) Pipeline to Europe. TANAP plays a crucial role in maintaining Energy Security for the region and Europe. In that respect, the application of Process Safety principles is vital to deliver safe, reliable and efficient Natural Gas delivery to Shippers both in the region and Europe. Effective Alarm Management is one of those Process Safety principles which feeds safe operations of the TANAP pipeline. Alarm Philosophy was designed and implemented in TANAP Pipeline according to the relevant standards. However, it is essential to manage the alarms received in the control room effectively to maintain safe operations. In that respect, TANAP has commenced Alarm Management & Rationalization program as of February 2022 after transferring to Plateau Regime, reaching the design parameters. While Alarm Rationalization started, there were more than circa 2300 alarms received per hour from one of the compressor stations. After applying alarm management principles such as reviewing and removal of bad actors, standing, stale, chattering, fleeting alarms, comprehensive review and revision of alarm set points through a change management principle, conducting alarm audits/design verification and etc., it has been achieved to reduce down to circa 40 alarms per hour. After the successful implementation of alarm management principles as specified above, the number of alarms has been reduced to industry standards. That significantly improved operator vigilance to focus on mainly important and critical alarms to avoid any excursion beyond safe operating limits leading to any potential process safety events. Following the ‟What Gets Measured, Gets Managed” principle, TANAP has identified key Performance Indicators (KPIs) to manage Process Safety principles effectively, where Alarm Management has formed one of the key parameters of those KPIs. However, review and analysis of the alarms were performed manually. Without utilizing Alarm Management Software, achieving full compliance with international standards is almost infeasible. In that respect, TANAP has started using one of the industry-wide known Alarm Management Applications to maintain full review and analysis of alarms and define actions as required. That actually significantly empowered TANAP’s process safety principles in terms of Alarm Management.

Keywords: process safety principles, energy security, natural gas pipeline operations, alarm rationalization, alarm management, alarm management application

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Authors: Mabruka S. Elashheb, Adullah Ali Bakush

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Schizophrenia is referred to as a disorder, not a disease, because there has not been any clear, reliable, and specific etiological factor. Even if schizophrenia is not a very frequent disease, it is among the most burdensome and costly illnesses worldwide. Prevention of relapse is a major goal of maintenance treatment in patients with psychotic disorders. We performed a comparison of a newer, atypical antipsychotic drug, Risperidone, and an older, conventional neuroleptic drug, Haloperidol, in terms of the effect on the usual kidney and liver functions and negative and positive symptoms in patients with schizophrenia and schizoaffective disorder after three and five weeks of their treatments. It is apparent from the comparative data of Haloperidol and Risperidone treatments in schizophrenic patients that Resperidone had superior improvement of negative and positive symptoms of patients, no harmful effect on liver and kidney functions and greater efficacy and faster recovery from schizophrenic symptoms in patients. On the basis of our findings of the present study, we concluded that treatment with Risperidone is superior to Haloperidol in reducing the risk of relapse among outpatients with schizophrenic disorders.

Keywords: schizophrenia, Haloperidol, Risperidone, positive and negative symptom

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Authors: Farah Fazlinda Binti Mohamad, Ahmad Saifizul Abdullah, Mohamed Rehan Karim , Jamilah Mohamad, Siti Hikmah Musthar

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Road safety is an important issue in Malaysia. It become important as it is discussed widely throughout printed and electronic media. Most of the news portrays on road accident and fatalities have increased the concern of everyone. This issue affects everyone's life as everyone shares the roads. The most vulnerable victims are the road user who uses the roads every day. It is appalling when World Health Organization (WHO) reported that in every 100,000 of population in Malaysia, 23 fatalities recorded due to road accident alone. This figure is quite alarming and requires serious attention. Furthermore, research by Malaysian Institute of Road Safety Research concluded that that speeding has contributed to 60% of all road accident in the country. Therefore, this study aims to elucidate the factors that influence road users’ speeding behaviour on selected roads in Peninsular Malaysia. To achieve this, set of questionnaires has distributed to 500 respondents on selected roads in Peninsular Malaysia. The respondents came from various demographic backgrounds in order to have a fair opinion on the issue. Using descriptive analysis, the results have indicated that psychological factors such as emotion and attitude of road user are the prominent factors that influence the road user’s speeding behaviour. Furthermore, the results have shown that male road users were dominant in speeding compared to female, which led to increased vulnerability to road injuries and fatalities. These findings are very useful in order for us to understand road users’ driving behaviour. Relevant authorities should also revise the existing countermeasures and find ways to reduce road accident. Engineers and road experts could cooperate in designing new road specifications for the road user. Nevertheless, it is important to comprehend this speeding issue and factors associated with it. Each road user should take this matter seriously and responsibly as road safety is a responsibility of all.

Keywords: countermeasures, psychological, road safety, speeding

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Authors: Surajj Sarode, G. Vidya Sagar, G. P. Vadnere

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The purpose of the present study was to prolong the gastric residence time of Stavudine by developing gastric floating drug delivery system (GFDDS). Moreover, to study influence of different polymers on its release rate using gas-forming agents, like sodium bicarbonate, citric acid. Floating tablets were prepared by wet granulation method using PVP K-30 as a binder and the other polymers include Pullulan Gum, HPMC K100M, six different formulations with the varying concentrations of polymers were prepared and the tablets were evaluated in terms of their pre-compression parameters like bulk density, tapped density, Haunsner ratio, angle of repose, compressibility index, post compression physical characteristics, in vitro release, buoyancy, floating lag time (FLT), total floating time (TFT) and swelling index. All the formulations showed good floating lag time i.e. less than 3 mins. The batch containing combination of Pullulan Gum and HPMC 100M (i.e. F-6) showed total floating lag time more than 12 h., the highest swelling index among all the prepared batches. The drug release was found to follow zero order kinetics.

Keywords: Suavudine, floating, total floating time (TFT), gastric residence

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Authors: Ismail Karaca, Ridvan Saracoglu, Omer Soner

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Fuzzy Logic, an advanced method to support decision-making, is used by various scientists in many disciplines. Fuzzy programming is a product of fuzzy logic, fuzzy rules, and implication. In marine science, fuzzy programming for ships is dramatically increasing together with autonomous ship studies. In this paper, a program to support the decision-making process for ship navigation has been designed. The program is produced in fuzzy logic and rules, by taking the marine accidents and expert opinions into account. After the program was designed, the program was tested by 46 ship accidents reported by the Transportation Safety Investigation Center of Turkey. Wind speed, sea condition, visibility, day/night ratio have been used as input data. They have been converted into a risk factor within the Fuzzy Logic Designer application and fuzzy rules set by marine experts. Finally, the expert's meteorological risk factor for each accident is compared with the program's risk factor, and the error rate was calculated. The main objective of this study is to improve the navigational safety of ships, by using the advance decision support model. According to the study result, fuzzy programming is a robust model that supports safe navigation.

Keywords: calculation of risk factor, fuzzy logic, fuzzy programming for ship, safety navigation of ships

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Authors: S. K. Balashanmugam, Padmavati Manchikanti, S. R. Subramanian

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The question of legal liability over injury arising out of the import and the introduction of GM food emerges as a crucial issue confronting to promote GM food and its derivatives. There is a greater possibility of commercialized GM food from the exporting country to enter importing country where status of approval shall not be same. This necessitates the importance of fixing a liability mechanism to discuss the damage, if any, occurs at the level of transboundary movement or at the market. There was a widespread consensus to develop the Cartagena Protocol on Biosafety and to give for a dedicated regime on liability and redress in the form of Nagoya Kuala Lumpur Supplementary Protocol on the Liability and Redress (‘N-KL Protocol’) at the international context. The national legal frameworks based on this protocol are not adequately established in the prevailing food legislations of the developing countries. The developing economy like India is willing to import GM food and its derivatives after the successful commercialization of Bt Cotton in 2002. As a party to the N-KL Protocol, it is indispensable for India to formulate a legal framework and to discuss safety, liability, and regulatory issues surrounding GM foods in conformity to the provisions of the Protocol. The liability mechanism is also important in the case where the risk assessment and risk management is still in implementing stage. Moreover, the country is facing GM infiltration issues with its neighbors Bangladesh. As a precautionary approach, there is a need to formulate rules and procedure of legal liability to discuss any kind of damage occurs at transboundary trade. In this context, the proposed work will attempt to analyze the liability regime in the existing Food Safety and Standards Act, 2006 from the applicability and domestic compliance and to suggest legal and policy options for regulatory authorities.

Keywords: commercialization, food safety, FSSAI, genetically modified foods, India, liability

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