Search results for: drug safety

Authors: Seyran Naghdi

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Background: Orphan drug development is limited by very high costs attributed to the research and development and small size market. How health policymakers address this challenge to consider both supply and demand sides need to be explored for directing the policies and plans in the right way. The price is an important signal for pharmaceutical companies’ profitability and the patients’ accessibility as well. Objective: This study aims to find out the orphan drugs' price-setting patterns and approaches in health systems through a systematic review of the available evidence. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) approach was used. MedLine, Embase, and Web of Sciences were searched via appropriate search strategies. Through Medical Subject Headings (MeSH), the appropriate terms for pricing were 'cost and cost analysis', and it was 'orphan drug production', and 'orphan drug', for orphan drugs. The critical appraisal was performed by the Joanna-Briggs tool. A Cochrane data extraction form was used to obtain the data about the studies' characteristics, results, and conclusions. Results: Totally, 1,197 records were found. It included 640 hits from Embase, 327 from Web of Sciences, and 230 MedLine. After removing the duplicates, 1,056 studies remained. Of them, 924 studies were removed in the primary screening phase. Of them, 26 studies were included for data extraction. The majority of the studies (>75%) are from developed countries, among them, approximately 80% of the studies are from European countries. Approximately 85% of evidence has been produced in the recent decade. Conclusions: There is a huge variation of price-setting among countries, and this is related to the specific pharmacological market structure and the thresholds that governments want to intervene in the process of pricing. On the other hand, there is some evidence on the availability of spaces to reduce the very high costs of orphan drugs development through an early agreement between pharmacological firms and governments. Further studies need to focus on how the governments could incentivize the companies to agree on providing the drugs at lower prices.

Keywords: orphan drugs, orphan drug production, pricing, costs, cost analysis

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Authors: Saeed Nazari, Masoom Nazari, Ali Hejazi, Siamak Sanoobari Ghazi Jahani, Mohammad Dehghani, Javad Vakili

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More than ever, digitization is an imperative for businesses to keep their competitive advantages, foster innovation and reduce paperwork. To design and successfully implement digital transformation initiatives within process safety management system, employees need to be equipped with the right tool, frameworks, and best practices. we developed a unique full stack application so-called SHEQTool which is entirely dynamic based on our extensive expertise, experience, and client feedback to help business processes particularly operations safety management. We use our best knowledge and scientific methodologies published by CCPS and OSHA Guidelines to streamline operations and integrated them into task management within Petrochemical Companies. We digitalize their main process safety management system elements and their sub elements such as hazard identification and risk management, training and communication, inspection and audit, critical changes management, contractor management, permit to work, pre-start-up safety review, incident reporting and investigation, emergency response plan, personal protective equipment, occupational health, and action management in a fully customizable manner with no programming needs for users. We review the feedback from main actors within petrochemical plant which highlights improving their business performance and productivity as well as keep tracking their functions’ key performance indicators (KPIs) because it; 1) saves time, resources, and costs of all paperwork on our businesses (by Digitalization); 2) reduces errors and improve performance within management system by covering most of daily software needs of the organization and reduce complexity and associated costs of numerous tools and their required training (One Tool Approach); 3) focuses on management systems and integrate functions and put them into traceable task management (RASCI and Flowcharting); 4) helps the entire enterprise be resilient to any change of your processes, technologies, assets with minimum costs (through Organizational Resilience); 5) reduces significantly incidents and errors via world class safety management programs and elements (by Simplification); 6) gives the companies a systematic, traceable, risk based, process based, and science based integrated management system (via proper Methodologies); 7) helps business processes complies with ISO 9001, ISO 14001, ISO 45001, ISO 31000, best practices as well as legal regulations by PDCA approach (Compliance).

Keywords: process, safety, digitalization, management, risk, incident, SHEQTool, OSHA, CCPS

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Authors: Parisa Shirzadeh

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Drug delivery systems in which drugs are traditionally used, multi-stage and at specified intervals by patients, do not meet the needs of the world's up-to-date drug delivery. In today's world, we are dealing with a huge number of recombinant peptide and protean drugs and analogues of hormones in the body, most of which are made with genetic engineering techniques. Most of these drugs are used to treat critical diseases such as cancer. Due to the limitations of the traditional method, researchers sought to find ways to solve the problems of the traditional method to a large extent. Following these efforts, controlled drug release systems were introduced, which have many advantages. Using controlled release of the drug in the body, the concentration of the drug is kept at a certain level, and in a short time, it is done at a higher rate. Graphene is a natural material that is biodegradable, non-toxic, and natural compared to carbon nanotubes; its price is lower than carbon nanotubes and is cost-effective for industrialization. On the other hand, the presence of highly effective surfaces and wide surfaces of graphene plates makes it more effective to modify graphene than carbon nanotubes. Graphene oxide is often synthesized using concentrated oxidizers such as sulfuric acid, nitric acid, and potassium permanganate based on Hummer 1 method. In comparison with the initial graphene, the resulting graphene oxide is heavier and has carboxyl, hydroxyl, and epoxy groups. Therefore, graphene oxide is very hydrophilic and easily dissolves in water and creates a stable solution. On the other hand, because the hydroxyl, carboxyl, and epoxy groups created on the surface are highly reactive, they have the ability to work with other functional groups such as amines, esters, polymers, etc. Connect and bring new features to the surface of graphene. In fact, it can be concluded that the creation of hydroxyl groups, Carboxyl, and epoxy and in fact graphene oxidation is the first step and step in creating other functional groups on the surface of graphene. Chitosan is a natural polymer and does not cause toxicity in the body. Due to its chemical structure and having OH and NH groups, it is suitable for binding to graphene oxide and increasing its solubility in aqueous solutions. Graphene oxide (GO) has been modified by chitosan (CS) covalently, developed for control release of doxorubicin (DOX). In this study, GO is produced by the hummer method under acidic conditions. Then, it is chlorinated by oxalyl chloride to increase its reactivity against amine. After that, in the presence of chitosan, the amino reaction was performed to form amide transplantation, and the doxorubicin was connected to the carrier surface by π-π interaction in buffer phosphate. GO, GO-CS, and GO-CS-DOX characterized by FT-IR, RAMAN, TGA, and SEM. The ability to load and release is determined by UV-Visible spectroscopy. The loading result showed a high capacity of DOX absorption (99%) and pH dependence identified as a result of DOX release from GO-CS nanosheet at pH 5.3 and 7.4, which show a fast release rate in acidic conditions.

Keywords: graphene oxide, chitosan, nanosheet, controlled drug release, doxorubicin

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Authors: L. R. Ferreira, R. Biscaro, C. C. Danziger, C. M. Galhardi, L. C. Biscaro, R. C. Biscaro, I. S. Vasconcelos, L. C. R. Ferreira, R. Reis, L. H. Oliveira

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Introduction: There is a worldwide trend for the employer to be aware of investing in health promotion that goes beyond occupational hygiene approaches with the implementation of a comprehensive program with integration between occupational health and safety, and social/psychosocial responsibility in the workplace. Work accommodation is a necessity in most companies as it allows the worker to return to its function respecting its physical limitations. This study had the objective to verify if the integration of health and safety in the companies, with the inclusion of the concept of TWH promoted by an occupational health service has impacted in the management of absenteeism of workers in work accommodation. Method: A retrospective and paired cohort study was used, in which the impact of the implementation of the Program for the Health/Safety Integration and Total Worker Health Concept (PHSITWHC) was evaluated using the indices of absenteeism, health attestations, days and hours of sick leave of workers that underwent job accommodation/rehabilitation. This was a cohort study and the data were collected from January to September of 2017, prior to the initiation of the integration program, and compared with the data obtained from January to September of 2018, after the implementation of the program. For the statistical analysis, the student's t-test was used, with statistically significant differences being made at p < 0.05. Results: The results showed a 35% reduction in the number of absenteeism rate in 2018 compared to the same period in 2017. There was also a significant reduction in the total numbers of days of attestations/absences (mean of 2,8) as well as days of attestations, absence and sick leaves (mean of 5,2) in 2018 data after the implementation of PHSITWHC compared to 2017 data, means of 4,3 and 25,1, respectively, prior to the program. Conclusion: It can be concluded that the inclusion of the PHSITWHC was associated with a reduction in the rate of absenteeism of workers that underwent job accommodation. It was observed that, once health and safety were approached and integrated with the inclusion of the TWH concept, it was possible to reduce absenteeism, and improve worker’s quality of life and wellness, and work accommodation management.

Keywords: absenteeism, health/safety integration, work accommodation management, total worker health

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Authors: Guldana Zhigerbayeva, Ming Yang

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Transportation of hazardous materials (HAZMAT) is inevitable in the process industries. The statistics show a significant number of accidents has occurred during the transportation of HAZMAT. This makes risk management of HAZMAT transportation an important topic. The tree-based methods including fault-trees, event-trees and cause-consequence analysis, and Bayesian network, have been applied to risk management of HAZMAT transportation. However, there is limited work on the development of a systematic approach. The existing approaches fail to build up the linkages between the regulatory requirements and the safety measures development. The analysis of historical data from the past accidents’ report databases would limit our focus on the specific incidents and their specific causes. Thus, we may overlook some essential elements in risk management, including regulatory compliance, field expert opinions, and suggestions. A systematic approach is needed to translate the regulatory requirements of HAZMAT transportation into specified safety measures (both technical and administrative) to support the risk management process. This study aims to first adapt the House of Quality (HoQ) to House of Safety (HoS) and proposes a new approach- Safety Function Deployment (SFD). The results of SFD will be used in a multi-criteria decision-support system to develop find an optimal route for HazMats transportation. The proposed approach will be demonstrated through a hypothetical transportation case in Kazakhstan.

Keywords: hazardous materials, risk assessment, risk management, quality function deployment

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

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

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

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Authors: Muhammad Naeem, Juho Lee, Jin-Wook Yoo

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In this study, we hypothesized that prolonged gastrointestinal transit at the inflamed colon conferred by a pH-triggered mucoadhesive smart nanoparticulate drug delivery system aids in achieving selective and sustained levels of the drug within the inflamed colon for the treatment of ulcerative colitis. We developed budesonide-loaded pH-sensitive charge-reversal solid lipid nanoparticles (SLNs) using a hot homogenization method. Polyetylenimine (PEI) was used to render SLNs cationic (PEI-SLNs). Eudragit S100 (ES) was coated on PEI-SLNs for pH-trigger charge-reversal SLNs (ES-PEI-SLNs). Therapeutic potential of the prepared SNLs formulation was evaluated in ulcerative colitis in mice. The transmission electron microscopy, zeta size and zeta potential data showed the successful formation of SLNs formulations. SLNs and PEI-SLNs showed burst drug release in acidic pH condition mimicking stomach and early small intestine environment which limiting their application as oral delivery systems. However, ES-PEI-SLNs prevented a burst drug release in acidic pH conditions and showed sustained release at a colonic pH. Most importantly, the surface charge of ES-PEI-SLNs switched from negative to positive in colonic conditions by pH-triggered removal of ES coating and accumulated selectively in inflamed colon. Furthermore, a charge reversal ES-PEI-SLNs showed a superior mitigation of dextran sulfate sodium (DSS)-induced acute colitis in mice as compared to SLNs and PEI-SLNs treated groups. Moreover, histopathological analysis of distal colon sections stained with hematoxylin/eosin and E-cadherin immunostaining revealed attenuated inflammation in an ES-PEI-SLNs-treated group. We also found that ES-PEI-SLNs markedly reduced the myeloperoxidase level and expression of TNF-alpha in colon tissue. Our results suggest that the pH-triggered charge reversal SLNs presented in this study would be a promising approach for ulcerative colitis therapy.

Keywords: solid lipid nanoparticles, stimuli-triggered charge-reversal, ulcerative colitis, methacrylate copolymer, budesonide

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Authors: Osama K. Abou-Zied, Saba A. Sulaiman

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We studied the spectroscopy of 25-nm diameter gold nanoparticles (AuNPs), coated with human serum albumin (HSA) as a model drug carrier. The morphology and coating of the AuNPs were examined using transmission electron microscopy and dynamic light scattering. Resonance energy transfer from the sole tryptophan of HSA (Trp214) to the AuNPs was observed in which the fluorescence quenching of Trp214 is dominated by a static mechanism. Using fluorescein (FL) to probe the warfarin drug-binding site in HSA revealed the unchanged nature of the binding cavity on the surface of the AuNPs, indicating the stability of the protein structure on the metal surface. The transient absorption results of the surface plasmonic resonance (SPR) band of the AuNPs show three ultrafast dynamics that are involved in the relaxation process after excitation at 460 nm. The three decay components were assigned to the electron-electron (~ 400 fs), electron-phonon (~ 2.0 ps) and phonon-phonon (200–250 ps) interactions. These dynamics were not changed upon coating the AuNPs with HSA which indicates the chemical and physical stability of the AuNPs upon bioconjugation. Binding of FL in HSA did not have any measurable effect on the bleach recovery dynamics of the SPR band, although both FL and AuNPs were excited at 460 nm. The current study is important for a better understanding of the physical and dynamical properties of protein-coated metal nanoparticles which are expected to help in optimizing their properties for critical applications in nanomedicine.

Keywords: gold nanoparticles, human serum albumin, fluorescein, femtosecond transient absorption

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Authors: Abdelhadi Adam Salih Denei

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Silver nanoparticles (AgNPs) have been used in cancer therapy, and the area of nanomedicine has made unheard-of strides in recent years. A thorough summary of the development and assessment of AgNPs for their possible use in the fight against cancer is the goal of this review. Targeted delivery methods have been designed to optimise therapeutic efficacy by using AgNPs' distinct physicochemical features, such as their size, shape, and surface chemistry. Firstly, the study provides an overview of the several synthesis routes—both chemical and green—that are used to create AgNPs. Natural extracts and biomolecules are used in green synthesis techniques, which are becoming more and more popular since they are biocompatible and environmentally benign. It is next described how synthesis factors affect the physicochemical properties of AgNPs, emphasising how crucial it is to modify these parameters for particular therapeutic uses. An extensive analysis is conducted on the anticancer potential of AgNPs, emphasising their capacity to trigger apoptosis, impede angiogenesis, and alter cellular signalling pathways. The analysis also investigates the potential benefits of combining AgNPs with currently used cancer treatment techniques, including radiation and chemotherapy. AgNPs' safety profile for use in clinical settings is clarified by a comprehensive evaluation of their cytotoxicity and biocompatibility.

Keywords: silver nanoparticles, cancer, nanocarrier system, targeted delivery

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Authors: Rathna Malhotra Gaur

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Owing to multiplicity and competition in the Indian food industry, it was always important for the government of India to bring in reforms that would protect the interest of the consumer and also the food operator. To further this objective, Food Safety, and Standards Act, 2006 (hereinafter referred to as FSSAI) was enacted for laying down science-based standards for articles and food and to regulate their storage, distribution, manufacture, same and import and to ensure safe food availability to the citizens of India. One of the safeguards towards consumer interest is the enactment of Food Safety and Standards (Licensing and Registration of Food Businesses, Regulation, 2011 within the mandate of FSSAI. It is mandatory for every food operator in India to get the registration certificate and procurement of food Licenses before starting operations in the country. All the nuances pertaining to the procurement of licenses are dealt with under these regulations. These regulations also lay down detailed provisions with regard to the conditions that the operator has to adhere to once the License is procured, going to the integrities of the safety and hygiene standards to be maintained by the food operators. This paper is an exhaustive effort to examine the provisions of obtaining the registration and License in India and the conditions that need to be fulfilled subsequently and further on the validity and renewal of these Food Licenses.

Keywords: food laws, food licenses, food registration, penalty

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Authors: Mohammed Muzafar, Darshan Ruikar

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BIM, an acronym for Building Information Modelling relates to the practice of creating a computer generated model which is capable of displaying the planning, design, construction and operation of a structure. The resulting simulation is a data-rich, object-oriented, intelligent and parametric digital representation of the facility, from which views and data, appropriate to various users needs can be extracted and analysed to generate information that can be used to make decisions and to improve the process of delivering the facility. BIM also refers to a shift in culture that will influence the way the built environment and infrastructure operates and how it is delivered. One of the main issues of concern in the construction industry at present in the UK is its record on Health & Safety (H&S). It is, therefore, important that new technologies such as BIM are developed to help improve the quality of health and safety. Historically the H&S record of the construction industry in the UK is relatively poor as compared to the manufacturing industries. BIM and the digital environment it operates within now allow us to use design and construction data in a more intelligent way. It allows data generated by the design process to be re-purposed and contribute to improving efficiencies in other areas of a project. This evolutionary step in design is not only creating exciting opportunities for the designers themselves but it is also creating opportunity for every stakeholder in any given project. From designers, engineers, contractors through to H&S managers, BIM is accelerating a cultural change. The paper introduces the concept behind a research project that mitigates the H&S risks associated with the construction, operation and maintenance of assets through the adoption of BIM.

Keywords: building information modeling, BIM levels, health, safety, integration

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Authors: Ndivhudzannyi Rembuluwani, Francis Dacosta, Emmanuel Mhlongo

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The small-scale rock aggregate sector of the mining industry is a major source of employment for a significant number of people, particularly in remote rural areas, where alternative livelihoods are rare. It contributes to local economy by generating income and producing major and essential materials for the building, construction, and other industries. However, the sector is confronted with many challenges that hamper productivity and growth. The problems that confront this sector includes: health and safety, environmental impacts, low production and low adherence to mining legislations. This study investigated the challenges confronting selected small-scale rock aggregate mines in the Vhembe District of Limpopo province of South Africa, assesses the health, safety, low production and environmental impacts associated with aggregate production and to develop an integrated approach of addressing the multi-faceted challenges.

Keywords: health and safety, legislative framework, productivity, rock aggregate, small-scale mining

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Authors: S. S. Pati, L. Herojit Singh, A. C. Oliveira, V. K. Garg

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Chitosan functionalized Fe3O4-Au core shell nanoparticles have been prepared using a two step wet chemical approach using NaBH4 as reducing agent for formation of Au inethylene glycol. X-ray diffraction studies shows individual phases of Fe3O4 and Au in the as prepared samples with crystallite size of 5.9 and 11.4 nm respectively. The functionalization of the core-shell nanostructure with Chitosan has been confirmed using Fourier transform infrared spectroscopy along with signatures of octahedral and tetrahedral sites of Fe3O4 below 600cm-1. Mössbauer spectroscopy shows decrease in particle-particle interaction in presence of Au shell (72% sextet) than pure oleic coated Fe3O4 nanoparticles (88% sextet) at room temperature. At 80K, oleic acid coated Fe3O4 shows only sextets whereas the Chitosan functionalized Fe3O4 and Chitosan functionalized Fe3O4@Au core shell show presence of 5 and 11% doublet, respectively.

Keywords: core shell, drug delivery, gold nanoparticles, magnetic nanoparticles

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Authors: Wadha Alqahtani

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In recent times, polymers have seen a great surge in interest in the field of medicine, particularly chemotherapeutics. One recent innovation is the conversion of polymeric materials into “polymeric nanoparticles”. These nanoparticles can be designed and modified to encapsulate and transport drugs selectively to cancer cells, minimizing collateral damage to surrounding healthy tissues, and improve patient quality of life. In this study, we have synthesized pseudo-branched polyester polymers from bio-based small molecules, including sorbitol, glutaric acid and a propargylic acid derivative to further modify the polymer to make it “click-able" with an azide-modified target ligand. Melt polymerization technique was used for this polymerization reaction, using lipase enzyme catalyst NOVO 435. This reaction was conducted between 90- 95 °C for 72 hours. The polymer samples were collected in 24-hour increments for characterization and to monitor reaction progress. The resulting polymer was purified with the help of methanol dissolving and filtering with filter paper then characterized via NMR, GPC, FTIR, DSC, TGA and MALDI-TOF. Following characterization, these polymers were converted to a polymeric nanoparticle drug delivery system using solvent diffusion method, wherein DiI optical dye and chemotherapeutic drug Taxol can be encapsulated simultaneously. The efficacy of the nanoparticle’s apoptotic effects were analyzed in-vitro by incubation with prostate cancer (LNCaP) and healthy (CHO) cells. MTT assays and fluorescence microscopy were used to assess the cellular uptake and viability of the cells after 24 hours at 37 °C and 5% CO2 atmosphere. Results of the assays and fluorescence imaging confirmed that the nanoparticles were successful in both selectively targeting and inducing apoptosis in 80% of the LNCaP cells within 24 hours without affecting the viability of the CHO cells. These results show the potential of using biodegradable polymers as a vehicle for receptor-specific drug delivery and a potential alternative for traditional systemic chemotherapy. Detailed experimental results will be discussed in the e-poster.

Keywords: chemotherapeutic drug, click chemistry, nanoparticle, prostat cancer

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Authors: Ho Young Son, Bu Seog Ju, Woo Young Jung

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This study presents the seismic safety evaluation of weir structure subjected to strong earthquake ground motions, as a flood defense structure in civil engineering structures. The seismic safety analysis procedure was illustrated through development of Finite Element (FE) and InFinite Element (IFE) method in ABAQUS platform. The IFE model was generated by CINPS4, 4-node linear one-way infinite model as a sold continuum infinite element in foundation areas of the weir structure and then nonlinear FE model using friction model for soil-structure interactions was applied in this study. In order to understand the complex behavior of weir structures, nonlinear time history analysis was carried out. Consequently, it was interesting to note that the compressive stress gave more vulnerability to the weir structure, in comparison to the tensile stress, during an earthquake. The stress concentration of the weir structure was shown at the connection area between the weir body and stilling basin area. The stress both tension and compression was reduced in IFE model rather than FE model of weir structures.

Keywords: seismic, numerical analysis, FEM, weir, boundary condition

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Authors: Taimaz Larimian, Negin Sadeghi

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Very little is known about the impacts of urban security on the level of social sustainability within the cities of developing countries. Urban security is still struggling to find its position in the social sustainability agenda, despite the significant role of safety and security on different aspects of peoples’ lives. This paper argues that urban safety and security should be better integrated within the social sustainability framework. With this aim, this study investigates the hypothesized relationship between social sustainability and Crime Prevention through Environmental Design (CPTED) approach at the neighborhood scale. This study proposes a model of key influential dimensions of CPTED analyzed into localized factors and sub-factors. These factors are then prioritized using pairwise comparison logic and fuzzy group Analytic Hierarchy Process (AHP) method in order to determine the relative importance of each factor on achieving social sustainability. The proposed model then investigates social sustainability in six case study neighborhoods of Isfahan city based on residents’ perceptions of safety within their neighborhood. Mixed method of data collection is used by using a self-administered questionnaire to explore the residents’ perceptions of social sustainability in their area of residency followed by an on-site observation to measure the CPTED construct. In all, 150 respondents from selected neighborhoods were involved in this research. The model indicates that CPTED approach has a significant direct influence on increasing social sustainability in neighborhood scale. According to the findings, among different dimensions of CPTED, ‘activity support’ and ‘image/ management’ have the most influence on people’s feeling of safety within studied areas. This model represents a useful designing tool in achieving urban safety and security during the development of more socially sustainable and user-friendly urban areas.

Keywords: crime prevention through environmental design (CPTED), developing countries, fuzzy analytic hierarchy process (FAHP), social sustainability

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Authors: Satya Eswari Jujjavarapu, Swast Dhagat

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Contagious diseases enact severe public health problems and have upsetting consequences. The cyclic lipopeptides explained by bacteria Bacillus, Paenibacillus, Pseudomonas, Streptomyces, Serratia, Propionibacterium and fungus Fusarium are very critical in confining the pathogens. As the degree of drug resistance upsurges in unparalleled manner, the perseverance of searching novel cyclic lipopeptides is being professed. The intense study has shown the implication of these bioactive compounds extending beyond antibacterial and antifungal. Lipopeptides, composed of single units of peptide and fatty acyl moiety, show broad spectrum antimicrobial effects. Among the surplus of cyclic lipopeptides, only few have materialized as strong antibiotics. For their functional vigor, polymyxin, daptomycin, surfactin, iturin and bacillomycin have been integrated in mainstream healthcare. In our work daptomycin has been a major part of antimicrobial resource since the past decade. Daptomycin, a cyclic lipopeptide consists of 13-member amino acid with a decanoyl side-chain. This structure of daptomycin confers it the mechanism of action through which it forms pore in the bacterial cell membrane resulting in the death of cell. Daptomycin is produced by Streptococccus roseoporus and acts against Streptococcus pneumonia (PSRP), methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). The PDB structure and ligands of daptomycin are available online. The molecular docking studies of these ligands with the lipopeptides were performed and their docking score and glide energy were recorded.

Keywords: daptomycin, molecular docking, structure-based drug design, lipopeptide

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Authors: Shamill Amedot Udonwa, Phyllis S. Y. Chong, Lim S. L. Julia, Wee-Joo Chng

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In this paper, we investigated how PRL-3 expression in H929 and U266 cells affects the efficacy of drug treatment. H929 and U266 cells were treated with Bortezomib (BTZ) of different concentrations, and it was observed that H929 cells were resistant to BTZ, while U266 cells were not viable. Investigations into how BTZ targets these cells were conducted, and it was observed that BTZ affects the PARP-Caspase3 pathway as well as PRL-3-Leo1 pathways. These pathways regulate cell proliferation and cell cycle, respectively. Hence, we are able to show the mechanism of how BTZ affects cells and also the role PRL-3 plays on downstream oncogenes such as cyclin-D1 and c-MYC. More importantly, this investigation into PRL-3 in BTZ resistance will be highly applicable in the future as the first clinical trials of PRL-3 antibody (PRL3-zumab) are ongoing at the National University Hospital, Singapore (NUHS). This would mean that understanding the mechanism of resistance through PRL-3, which has yet to be studied, will demonstrate the potential of PRL-3 in developing novel strategies to improve the treatment of MM.

Keywords: drug resistance, hematology, multiple myeloma, oncogene

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Authors: Deonie Botha

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Digital transformation and the digitization of occupational health and safety training have grown exponentially due to a variety of contributing factors. The literature suggests that digitalization has numerous benefits but also has associated challenges. The aim of the paper is to develop an understanding of both the perceived benefits and challenges of digitalization in an occupational health and safety context in an effort to design and develop e-learning interventions that will optimize the benefits of digitalization and address the associated challenges. The paper proposes, deliberate and tests the design principles of an e-learning intervention to ensure alignment with the requirements of a digitally transformed environment. The results of the research are based on a literature review regarding the requirements and effect of the Fourth Industrial Revolution on learning and e-learning in particular. The findings of the literature review are enhanced with empirical research in the form of a case study conducted in an organization that designs and develops e-learning content in the occupational health and safety industry. The primary findings of the research indicated that: (i) The requirements of learners and organizations in respect of e-learning are different than previously (i.e., a pre-Fourth Industrial Revolution related work setting). (ii) The design principles of an e-learning intervention need to be aligned with the entire value chain of the organization. (iii) Digital twins support and enhance the design and development of e-learning. (iv)Learning should incorporate a multitude of sensory experiences and should not only be based on visual stimulation. (v) Data that are generated as a result of e-learning interventions should be incorporated into big data streams to be analyzed and to become actionable. It is therefore concluded that there is general consensus on the requirements that e-learning interventions need to adhere to in a digitally transformed occupational health and safety work environment. The challenge remains for organizations to incorporate data generated as a result of e-learning interventions into the digital ecosystem of the organization.

Keywords: digitalization, training, fourth industrial revolution, big data

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Authors: Moise A.E., State G., Tudorache M., Custură I., Enea D.N., Osman (Defta) A., Drăgotoiu D.

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This scientific paper explores risk management strategies in the food supply chain, with a focus on chicken raw materials, in the context of a company sourcing from the EU and non-EU. The aim of the paper is to adapt the requirements of international standards (IFS, BRC, QS, ITW, FSSC, ISO), proposing efficient methods to identify and remediate non-conformities and corrective and preventive actions. Defining the supply flow and acceptance steps promotes collaboration with suppliers to ensure the quality and safety of raw materials. To assess the risks of suppliers and raw materials, objective criteria are developed and vulnerabilities in the supply chain are analyzed, including the risk of fraud. Active monitoring of international alerts through RASFF helps to identify emerging risks quickly, and regular analysis of international trends and company performance enables continuous adaptation of risk management strategies. Implementing these measures strengthens food safety and consumer confidence in the final products supplied.

Keywords: food supply chain, international standards, quality and safety of raw materials, RASFF

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Authors: Louise Penzenstadler, Tiphaine Robet, Radu Iuga, Daniele Zullino

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Context: The outpatient clinic of the psychiatric addiction service of Geneva University Hospital has been providing support to individuals affected by various narcotics for 30 years. However, the increasing consumption of crack cocaine in Geneva has presented a new challenge for the healthcare system. Research Aim: The aim of this research is to evaluate the impact of an outreach intervention on crack cocaine addiction in users with co-occurring opioid use disorder. Methodology: The research utilizes a combination of quantitative and qualitative retrospective data analysis to evaluate the effectiveness of the outreach intervention. Findings: The data collected from October 2023 to December 2023 show that the outreach program successfully made 1,071 contacts with drug users and led to 15 new requests for care and enrollment in treatment. Patients expressed high satisfaction with the intervention, citing easy and rapid access to treatment and social support. Theoretical Importance: This research contributes to the understanding of the challenges and specific needs of a complex group of drug users who face severe health problems. It highlights the importance of outreach interventions in establishing trust, connecting users with care, and facilitating medication-assisted treatment for opioid addiction. Data Collection: Data was collected through the outreach program's interactions with drug users, including street outreach interventions and presence at locations frequented by users. Patient satisfaction surveys were also utilized. Analysis Procedures: The collected data was analyzed using both quantitative and qualitative methods. The quantitative analysis involved examining the number of contacts made, new requests for care, and treatment enrollment. The qualitative analysis focused on patient satisfaction and their perceptions of the intervention. Questions Addressed: The research addresses the following questions: What is the impact of an outreach intervention on crack cocaine addiction in users with co-occurring opioid use disorder? How effective is the outreach program in connecting drug users with care and initiating medication-assisted treatment? Conclusion: The outreach program has proven to be an effective intervention in establishing trust with crack users, connecting them with care, and initiating medication-assisted treatment for opioid addiction. It has also highlighted the importance of addressing the specific challenges faced by this group of drug users.

Keywords: crack addiction, outreach treatment, peer intervention, polydrug use

Procedia PDF Downloads 46

Authors: Shazia Bano

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Nanoconjugates that integrate photo-based therapeutics and diagnostics within a single platform promise great advances in revolutionizing cancer treatments. However, to achieve high therapeutic efficacy, designing functionally efficacious nanocarriers to tightly retain the drug, promoting selective drug localization and release, and the validation of the efficacy of these nanoconjugates is a great challenge. Here we have designed smart multiagent, liposome based targeted photoactivatable multiagent nanoconjugates, doped with a photoactivatable chromophore benzoporphyrin derivative (BPD) labelled with an active targeting ligand cetuximab to target the EGFR receptor (over expressed in various cancer cells) to deliver a combination of therapeutic agents. This study establishes a tunable nanoplatform for the delivery of the photoactivatable multiagent nanoconjugates for tumor-specific accumulation and targeted destruction of cancer cells in complex cancer model to enhance the therapeutic index of the administrated drugs.

Keywords: targeting, photodynamic therapy, photoactivatable, nanoconjugates

Procedia PDF Downloads 126

Authors: Anurag Gaur Nidhi

Abstract:

Targeted drug delivery is a method of delivering medication to a patient in a manner that increases the concentration of the medication in some parts of the body relative to others. Targeted drug delivery seeks to concentrate the medication in the tissues of interest while reducing the relative concentration of the medication in the remaining tissues. This improves efficacy of the while reducing side effects. In the present work, we investigate the effect of magnetic field, flow rate and particle concentration on the capturing of magnetic particles transported in a stent implanted fluidic channel. Iron oxide magnetic nanoparticles (Fe3O4) nanoparticles were synthesized via co-precipitation method. The synthesized Fe3O4 nanoparticles were added in the de-ionized (DI) water to prepare the Fe3O4 magnetic particle suspended fluid. This fluid is transported in a cylindrical tube of diameter 8 mm with help of a peristaltic pump at different flow rate (25-40 ml/min). A ferromagnetic coil of SS 430 has been implanted inside the cylindrical tube to enhance the capturing of magnetic nanoparticles under magnetic field. The capturing of magnetic nanoparticles was observed at different magnetic magnetic field, flow rate and particle concentration. It is observed that capture efficiency increases from 47-67 % at magnetic field 2-5kG, respectively at particle concentration 0.6 mg/ml and at flow rate 30 ml/min. However, the capture efficiency decreases from 65 to 44 % by increasing the flow rate from 25 to 40 ml/min, respectively. Furthermore, it is observed that capture efficiency increases from 51 to 67 % by increasing the particle concentration from 0.3 to 0.6 mg/ml, respectively.

Keywords: capture efficiency, implant assisted-Magnetic drug targeting (IA-MDT), magnetic nanoparticles, In-vitro study

Procedia PDF Downloads 288

Authors: Soheila Ghanbari

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After the Civil Rights Act of 1964 was enacted, federal policy transformed employment rights. Equal employment opportunity law, legislation for occupational safety and health, and regulations for fringe benefits were established to ensure that employees have rights to equal protection, health and safety, and the benefits guaranteed by employers. In research analyzing data from 279 organizations over time, it was discovered that legal changes prompted organizations to establish personnel, antidiscrimination, safety, and benefits departments to ensure compliance. However, as the process of institutionalization advanced, middle managers began to separate these fresh offices from policy and rationalize them solely in economic terms as a component of the new human resources management model. This common occurrence is seen in the United States, where the Constitution represents government control of business as unlawful. It could potentially clarify the extended lack of a state theory in organizational analysis and shed light on a puzzle pointed out by state theorists: the federal state is weak in terms of administration but strong in terms of norms.

Keywords: management, state, human, resources, employment

Procedia PDF Downloads 24

Authors: Anastasios Manos, Despina Elisabeth Filippidou

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Introduction: Historical buildings are an inte-gral part of the cultural heritage of every place, and beyond the obvious need for protection against risks, they have specific requirements regarding the handling of hazards and disasters such as fire, floods, earthquakes, etc. Ensuring high levels of protection and safety for these buildings is impera-tive for two distinct but interconnected reasons: a) they themselves constitute cultural heritage, and b) they are often used as museums/cultural spaces, necessitating the protection of both human life (vis-itors and workers) and the cultural treasures they house. However, these buildings present serious constraints in implementing the necessary measures to protect them from destruction due to their unique architecture, construction methods, and/or the structural materials used in the past, which have created an existing condition that is sometimes challenging to reshape and operate within the framework of modern regulations and protection measures. One of the most devastating risks that threaten historical buildings is fire. Catastrophic fires demonstrate the need for timely evaluation of fire safety measures in historical buildings. Recog-nizing the criticality of protecting historical build-ings from the risk of fire, the Confederation of Fire Protection Associations in Europe (CFPA E) issued specific guidelines in 2013 (CFPA-E Guideline No 30:2013 F) for the fire protection of historical buildings at the European level. However, until now, few actions have been implemented towards leveraging modern technologies in the field of con-struction and maintenance of buildings, such as Building Information Modeling (BIM) and the Inter-net of Things (IoT), for the protection of historical buildings from risks like fires, floods, etc. The pro-ject BIM4Cult has bee developed in order to fill this gap. It is a tool for timely assessing and monitoring of the fire safety level of historical buildings using BIM and IoT technologies in an integrated manner. The tool serves as a decision support expert system for improving the fire safety of historical buildings by continuously monitoring, controlling and as-sessing critical risk factors for fire.

Keywords: Iot, fire, BIM, expert system

Procedia PDF Downloads 49

Authors: Yassir Adam Shuaib, Stefan Niemann, Eltahir Awad Khalil, Ulrich Schaible, Lothar Heinz Wieler, Mohammed Ahmed Bakhiet, Abbashar Osman Mohammed, Mohamed Abdelsalam Abdalla, Elvira Richter

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Tuberculosis (TB) is a chronic bacterial disease of humans and animals and it is characterized by the progressive development of specific granulomatous tubercle lesions in affected tissues. In a six-month study, from June to November 2014, a total of 2,304 carcasses of cattle, camel, sheep, and goats slaughtered at East and West Gaash slaughterhouses, Kassala, were investigated during postmortem, in parallel, 101 sputum samples from TB suspected patients at Kassala and El-Gadarif Teaching Hospitals were collected in order to investigate tuberculosis in animals and humans. Only 0.1% carcasses were found with suspected TB lesions in the liver and lung and peritoneal cavity of two sheep and no tuberculous lesions were found in the carcasses of cattle, goats or camels. All samples, tissue lesions and sputum, were decontaminated by the NALC-NaOH method and cultured for mycobacterial growth at the NRZ for Mycobacteria, Research Center Borstel, Germany. Genotyping and molecular characterization of the grown strains were done by line probe assay (GenoType CM and MTBC) and 16S rDNA, rpoB gene, and ITS sequencing, spoligotyping, MIRU-VNTR typing and next generation sequencing (NGS). Culture of the specimens revealed growth of organisms from 81.6% of all samples. Mycobacterium tuberculosis (76.2%), M. intracellulare (14.2%), mixed infection with M. tuberculosis and M. intracellulare (6.0%) and mixed infection with M. tuberculosis and M. fortuitum and with M. intracellulare and unknown species (1.2%) were detected in the sputum samples and unknown species (1.2%) were detected in the samples of one of the animals tissues. From the 69 M. tuberculosis strains, 25 (36.2%) were showing either mono-drug-resistant or multi-drug-resistant or poly-drug-resistant but none was extensively drug-resistant. In conclusion, the prevalence of TB in animals was very low while in humans M. tuberculosis-Delhi/CAS lineage was responsible for most cases and there was an evidence of MDR transmission and acquisition.

Keywords: animal, human, slaughterhouse, Sudan, tuberculosis

Procedia PDF Downloads 349

Authors: Hoda Sabry Othman, Randa Helmy Swellem, Galal Abd El-Moein Nawwar

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N-cyanoacetyl glycine is a reactive polyfunctional precursor for synthesis of new difficult accessible compounds including pyridones, thiazolopyridine and others. The key step of this protocol is the formation of different ylidines which underwent Michael addition with carbon nucleophiles affording various heterocyclic compounds. Selected compounds underwent pharmacological evaluation, in vitro against two cell lines; breast cell line (MCF-7),and liver cell line(HEPG2). Compounds 14, 15a and 16 showed IC50 values 8.93, 8.18 and 8.03 (µ/ml) respectively for breast cell line (MCF-7), while the standard drug (Tamoxifen) revealed IC50 8.31. With respect to the liver cell line (HEPG2), compounds 14 and 15a revealed IC50 18.4 and 13.6(µ/ml) respectively while the IC50 of the standard drug(5-Flurouracil) is 25(µ/ml). The antimicrobial activity was also screened and revealed that oxime 7 and ylidine 9f showed a broad-spectrum activity.

Keywords: antitumor, cyanoacetyl glycine, heterocycles, pyridones

Procedia PDF Downloads 319

Authors: Lingzhi Li, Jiankun Zhang, Tiantian Gu

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Hazard management that can prevent fatal accidents and property losses is a fundamental process during the buildings’ construction stage. However, due to lack of safety supervision resources and operational pressures, the conduction of hazard management is poor and ineffective in China. In order to improve the quality of construction safety management, it is critical to explore the use of information technologies to ensure that the process of hazard management is efficient and effective. After exploring the existing problems of construction hazard management in China, this paper develops the griddization management model for construction hazard management. First, following the knowledge grid infrastructure, the griddization computing infrastructure for construction hazards management is designed which includes five layers: resource entity layer, information management layer, task management layer, knowledge transformation layer and application layer. This infrastructure will be as the technical support for realizing grid management. Second, this study divides the construction hazards into grids through city level, district level and construction site level according to grid principles. Last, a griddization management process including hazard identification, assessment and control is developed. Meanwhile, all stakeholders of construction safety management, such as owners, contractors, supervision organizations and government departments, should take the corresponding responsibilities in this process. Finally, a case study based on actual construction hazard identification, assessment and control is used to validate the effectiveness and efficiency of the proposed griddization management model. The advantage of this designed model is to realize information sharing and cooperative management between various safety management departments.

Keywords: construction hazard, griddization computing, grid management, process

Procedia PDF Downloads 256

Authors: Brandtner-Hafner Martin

Abstract:

Adhesives are increasingly being used in the construction sector. On the one hand, this concerns dowel reinforcements using chemical anchors. On the other hand, the sealing and repair of cracks in structural concrete components are still on the rise. In the field of bonding, the interface between the joined materials is the most critical area. Therefore, it is of immense importance to characterize and investigate this section sufficiently by fracture analysis. Since standardized mechanical test methods are not sufficiently capable of doing this, recourse is made to an innovative concept based on fracture energy. Therefore, a series of experimental tests were performed using the so-called GF-principle to study the interface bonding safety of adhesively bonded concrete joints. Several different structural adhesive systems based on epoxy, CA/A hybrid, PUR, MS polymer, dispersion, and acrylate were selected for bonding concrete substrates. The results show that stable crack propagation and prevention of uncontrolled failure in bonded concrete joints depend very much on the adhesive system used, and only fracture analytical evaluation methods can provide empirical information on this.

Keywords: interface bonding safety, adhesively bonded concrete joints, GF-principle, fracture analysis

Procedia PDF Downloads 291

Authors: Sao-Jeng Chao, Chia-Yun Wei, Si-Han Lai, Cheng-Yu Huang, Yu-Han Teng

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In Taiwan, the landforms are mainly dominated by mountains and hills. Many road sections of the National Highway are impossible to avoid problems such as slope excavation or slope filling. In order to increase the safety of the slope, various slope protection methods are used to stabilize the slope, especially the soil anchor technique is the most common. This study is inspired by the soil liquefaction potential map. The concept of the potential map is widely used. The typhoon, earth-rock flow, tsunami, flooded area, and the recent discussion of soil liquefaction have safety potential concepts. This paper brings the concept of safety potential to the anchored slope. Because the soil anchor inspection is only the concept of points, this study extends the concept of the point to the surface, using the Quantum GIS program to present the slope damage area, and depicts the slope appearance and soil anchor point with the slope as-built drawing. The soil anchor scores are obtained by anchor inspection data, and the low, medium and high potential areas are remitted by interpolation. Thus, the area where the anchored slope may be harmful is judged and relevant maintenance is provided. The maintenance units can thus prevent judgment and deal with the anchored slope as soon as possible.

Keywords: anchor, slope, potential map, lift-off test, existing load

Procedia PDF Downloads 124