Search results for: drug safety

Authors: Saurabh B. Ganorkar, Atul A. Shirkhedkar

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The need for investigations protecting against toxic impurities though seems to be a primary requirement; the impurities which may prove non - toxic can be explored for their therapeutic potential if any to assist advanced drug discovery. The essential role of pharmaceutical analysis can thus be extended effectively to achieve it. The present study successfully achieved these objectives with characterization of major degradation products as impurities for Zileuton which has been used for to treat asthma since years. The forced degradation studies were performed to identify the potential degradation products using Ultra-fine Liquid-chromatography. Liquid-chromatography-Mass spectrometry (Time of Flight) and Proton Nuclear Magnetic Resonance Studies were utilized effectively to characterize the drug along with five major oxidative and hydrolytic degradation products (DP’s). The mass fragments were identified for Zileuton and path for the degradation was investigated. The characterized DP’s were subjected to In-Silico studies as XP Molecular Docking to compare the gain or loss in binding affinity with 5-Lipooxygenase enzyme. One of the impurity of was found to have the binding affinity more than the drug itself indicating for its potential to be more bioactive as better Antiasthmatic. The close structural resemblance has the ability to potentiate or reduce bioactivity and or toxicity. The chances of being active biologically at other sites cannot be denied and the same is achieved to some extent by predictions for probability of being active with Prediction of Activity Spectrum for Substances (PASS) The impurities found to be bio-active as Antineoplastic, Antiallergic, and inhibitors of Complement Factor D. The toxicological abilities as Ames-Mutagenicity, Carcinogenicity, Developmental Toxicity and Skin Irritancy were evaluated using Toxicity Prediction by Komputer Assisted Technology (TOPKAT). Two of the impurities were found to be non-toxic as compared to original drug Zileuton. As the drugs are purposed and repurposed effectively the impurities can also be; as they can have more binding affinity; less toxicity and better ability to be bio-active at other biological targets.

Keywords: UFLC, LC-MS-TOF, NMR, Zileuton, impurities, toxicity, bio-activity

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Authors: Yogeeta O. Agrawal, Hitendra S. Mahajan, Sanjay J. Surana

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Methotrexate is effective in controlling recalcitrant psoriasis when administered by the oral or parenteral route long-term. However, the systematic use of this drug may provoke any of a number of side effects, notably hepatotoxic effects. To reduce these effects, clinical studies have been done with topical MTx. It is useful in treating a number of cutaneous conditions, including psoriasis. A major problem in topical administration of MTx currently available in market is that the drug is hydrosoluble and is mostly in the dissociated form at physiological pH. Its capacity for passive diffusion is thus limited. Localization of MTx in effected layers of skin is likely to improve the role of topical dosage form of the drug as a supplementary to oral therapy for treatment of psoriasis. One of the possibilities for increasing the penetration of drugs through the skin is the use of Nanostructured lipid Carriers. The objective of the present study was to formulate and characterize Methotrexate loaded Nanostructured Lipid Carriers (MtxNLCs), to understand in vitro drug release and evaluate the role of the developed gel in the topical treatment of psoriasis. MtxNLCs were prepared by solvent diffusion technique using 3(2) full factorial design.The mean diameter and surface morphology of MtxNLC was evaluated. MtxNLCs were lyophilized and crystallinity of NLC was characterized by Differential Scanning Calorimtery (DSC) and powder X-Ray Diffraction (XRD). The NLCs were incorporated in 1% w/w Carbopol 934 P gel base and in vitro skin deposition studies in Human Cadaver Skin were conducted. The optimized MtxNLCs were spherical in shape, with average particle size of 253(±9.92)nm, zeta potential of -30.4 (±0.86) mV and EE of 53.12(±1.54)%. DSC and XRD data confirmed the formation of NLCs. Significantly higher deposition of Methotrexate was found in human cadaver skin from MtxNLC gel (71.52 ±1.23%) as compared to Mtx plain gel (54.28±1.02%). Findings of the studies suggest that there is significant improvement in therapeutic index in treatment of psoriasis by MTx-NLCs incorporated gel base developed in this investigation over plain drug gel currently available in the market.

Keywords: methotrexate, psoriasis, NLCs, hepatotoxic effects

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Authors: Mandy Wilson, Emma Vieira, Jocelyn Jones, Alice V. Brown, Lindey Andrews, Louise Southalan, Jackie Oakley, Dorothy Bagshaw, Patrick Egan, Laura Dent, Duc Dau, Lucy Spanswick

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Alcohol and drug dependency are pertinent issues for those experiencing homelessness. This includes Aboriginal and Torres Strait Islander people, Australia’s traditional owners, living in Perth, Western Australia (WA). Societal narratives around the drivers behind drug and alcohol dependency in Aboriginal communities, particularly those experiencing homelessness, have been biased and unchanging, with little regard for complexity. This can include the idea that Aboriginal people have ‘chosen’ to use alcohol or other drugs without consideration for intergenerational trauma and the trauma of homelessness that may influence their choices. These narratives have flow-on impacts on policies and services that directly impact Aboriginal people experiencing homelessness. In 2021, we commenced a project which aimed to listen to and elevate the voices of 70-90 Aboriginal people experiencing homelessness in Perth. The project is community-driven, led by an Aboriginal Community Controlled Organisation in partnership with a university research institute. A community-ownership group of Aboriginal Elders endorsed the project’s methods, chosen to ensure their suitability for the Aboriginal community. In this paper, we detail these methods, including semi-structured interviews influenced by an Aboriginal yarning approach – an important style of conversation for Aboriginal people which follows cultural protocols; and photovoice – supporting people to share their stories through photography. Through these engagements, we detail the reasons Aboriginal people in Perth shared for using alcohol or other drugs while experiencing homelessness. These included supporting their survival on the streets, managing their mental health, and coping while on the journey to finding support. We also detail why they sought to discontinue alcohol and other drug use, including wanting to reconnect with family and changing priorities. Finally, we share how Aboriginal people experiencing homelessness have said they are impacted by their family’s alcohol and other drug use, including feeling uncomfortable living with a family who is drug and alcohol-dependent and having to care for grandchildren despite their own homelessness. These findings provide a richer understanding of alcohol and drug use for Aboriginal people experiencing homelessness in Perth, shedding light on potential changes to targeted policy and service approaches.

Keywords: Aboriginal and Torres Strait Islander peoples, alcohol and other drugs, homelessness, community-led research

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Authors: Abdul Matin, Muhammad Ajmal, Uzma Yunus, Noaman-ul Haq, Hafiz M. Shohaib, Ambreen G. Muazzam

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Carbon nanoparticles (CNPs) have unique properties that are useful for the diagnosis and treatment of cancer due to their precise properties like small size (ideal for delivery within the body) stability in solvent and tunable surface chemistry for targeted delivery. Here, highly fluorescent, monodispersed and water-soluble CNPs were synthesized directly from a suitable carbohydrate source (glucose and sucrose) by one-step acid assisted ultrasonic treatment at 35 KHz for 4 hours. This method is green, simple, rapid and economical and can be used for large scale production and applications. The average particle sizes of CNPs are less than 10nm and they emit bright and colorful green-blue fluorescence under the irradiation of UV-light at 365nm. The CNPs were characterized by scanning electron microscopy, fluorescent spectrophotometry, Fourier transform infrared spectrophotometry, ultraviolet-visible spectrophotometry and TGA analysis. Fluorescent CNPs were used as fluorescent probe and nano-carriers for anticancer drug. Functionalized CNPs (with ethylene diamine) were attached with anticancer drug-Methotrexate. In vitro bioactivity and biocompatibility of CNPs-drug conjugates was evaluated by LDH assay and Sulforhodamine B assay using human lung carcinoma cell lines (H157). Our results reveled that CNPs showed biocompatibility and CNPs-anticancer drug conjugates have shown potent cytotoxic effects and high antitumor activities in lung cancer cell lines. CNPs are proved to be excellent substitute for conventional drug delivery cargo systems and anticancer therapeutics in vitro. Our future studies will be more focused on using the same nanoparticles in vivo model system.

Keywords: carbon nanoparticles, carbon nanoparticles-methotrexate conjugates, human lung carcinoma cell lines, lactate dehydrogenase, methotrexate

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Authors: Jillian M. Hagel, Joseph E. Tucker, Peter J. Facchini

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With the aim of establishing a holistic approach for the treatment of central nervous system (CNS) disorders, we are pursuing a drug development program rapidly progressing through discovery and characterization phases. The drug candidates identified in this program are referred to as neuroplastogens owing to their ability to mediate neuroplasticity, which can be beneficial to patients suffering from anxiety, depression, or posttraumatic stress disorder. These and other related neuropsychiatric conditions are associated with the onset of neuronal atrophy, which is defined as a reduction in the number and/or productivity of neurons. The stimulation of neuroplasticity results in an increase in the connectivity between neurons and promotes the restoration of healthy brain function. We have synthesized a substantial catalogue of proprietary indolethylamine derivatives based on the general structures of serotonin (5-hydroxytryptamine) and psychedelic molecules such as N,N-dimethyltryptamine (DMT) and psilocin (4-hydroxy-DMT) that function as neuroplastogens. A primary objective in our screening protocol is the identification of derivatives associated with a significant reduction in hallucination, which will allow administration of the drug at a dose that induces neuroplasticity and triggers other efficacious outcomes in the treatment of targeted CNS disorders but which does not cause a psychedelic response in the patient. Both neuroplasticity and hallucination are associated with engagement of the 5HT2A receptor, requiring drug candidates differentially coupled to these two outcomes at a molecular level. We use novel and proprietary artificial intelligence algorithms to predict the mode of binding to the 5HT2A receptor, which has been shown to correlate with the hallucinogenic response. Hallucination is tested using the mouse head-twitch response model, whereas mouse marble-burying and sucrose preference assays are used to evaluate anxiolytic and anti-depressive potential. Neuroplasticity is assays using dendritic outgrowth assays and cell-based ELISA analysis. Pharmacokinetics and additional receptor-binding analyses also contribute the selection of lead candidates. A summary of the program is presented.

Keywords: neuroplastogen, non-hallucinogenic, drug development, anxiety, depression, PTSD, indolethylamine derivatives, psychedelic-inspired, 5-HT2A receptor, computational chemistry, head-twitch response behavioural model, neurite outgrowth assay

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Authors: V. Naga Sravan Kumar Varma, H. G. Shivakumar

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The aim of the study was to develop dual sensitive poly (N-isopropylacrylamide-co-acrylic acid) (PNA) nanogels(NGs) and studying its applications for Anti-Cancer therapy. NGs were fabricated by free radical polymerization using different amount of N-isopropylacrylamide and acrylic acid. A study for polymer composition over the effect on LCST in different pH was evaluated by measuring the absorbance at 500nm using UV spectrophotometer. Further selected NG’s were evaluated for change in hydrodynamic diameters in response to pH and temperature. NGs which could sharply respond to low pH value of cancer cells at body temperature were loaded with Fluorouracil (5-FU) using equilibrium swelling method and studied for drug release behaviour in different pH. A significant influence of NGs polymer composition over pH dependent LCST was observed. NGs which were spherical with an average particle size of 268nm at room temperature, shrinked forming an irregular shape when heated above to their respective LCST. 5FU loaded NGs did not intervene any difference in pH depended LCST behaviour of NGs. The in vitro drug release of NGs exhibited a pH and thermo-dependent control release. The cytoxicity study of blank carrier to MCF7 cell line showed no cytotoxicity. The results indicated that PNA NGs could be used as a potential drug carrier for anti-cancer therapy.

Keywords: pH and thermo-sensitive, nanogels, P(NIPAM-co-AAc), anti-cancer, 5-FU

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Authors: Leila Jafari, Viliam Makis

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In this paper, the joint optimization of the economic manufacturing quantity (EMQ), safety stock level, and condition-based maintenance (CBM) is presented for a partially observable, deteriorating system subject to random failure. The demand is stochastic and it is described by a Poisson process. The stochastic model is developed and the optimization problem is formulated in the semi-Markov decision process framework. A modification of the policy iteration algorithm is developed to find the optimal policy. A numerical example is presented to compare the optimal policy with the policy considering zero safety stock.

Keywords: condition-based maintenance, economic manufacturing quantity, safety stock, stochastic demand

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Authors: Kelly Jaunzems

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Social media is a powerful instrument of communication, enabling the presentation of information in multiple forms and modes, amplifying the interactions between people, organisations, and stakeholders, and increasing the range of communication channels available. Younger generations are highly engaged with social media and more likely to use this channel than any other to seek information. Given this, it may appear extraordinary that occupational safety and health professionals have yet to seriously engage with social media for communicating safety messages to younger audiences who, in many industries, might be statistically more likely to encounter more workplace harm or injury. Millennials, defined as those born between 1981-2000, have distinctive characteristics that also impact their interaction patterns rendering many traditional occupational safety and health communication channels sub-optimal or near obsolete. Used to immediate responses, 280-character communication, shares, likes, and visual imagery, millennials struggle to take seriously the low-tech, top-down communication channels such as safety noticeboards, toolbox meetings, and passive tick-box online inductions favoured by traditional OSH professionals. This paper draws upon well-established communication findings, which argue that it is important to know a target audience and reach them using their preferred communication pathways, particularly if the aim is to impact attitudes and behaviours. Health practitioners have adopted social media as a communication channel with great success, yet safety practitioners have failed to follow this lead. Using a digital ethnography approach, this paper examines seven organisations’ Facebook posts from two one-month periods one year apart, one in 2018 and one in 2019. Each of the years informs organisation-based case studies. Comparing, contrasting, and drawing upon these case studies, the paper discusses and evaluates the (non) use of social media communication of safety information in terms of user engagement, shareability, and overall appeal. The success of health practitioners’ use of social media provides a compelling template for the implementation of social media into organisations’ safety communication strategies. Highly visible content such as that found on social media allows an organization to become more responsive and engage in two-way conversations with their audience, creating more engaged and participatory conversations around safety. Further, using social media to address younger audiences with a range of tonal qualities (for example, the use of humour) can achieve cut through in a way that grim statistics fail to do. On the basis of 18 months of interviews, filed work, and data analysis, the paper concludes with recommendations for communicating safety information via social media. It proposes exploration of the social media communication formula that, when utilised by safety practitioners, may create an effective social media presence. It is anticipated that such social media use will increase engagement, expand the number of followers and reduce the likelihood and severity of safety-related incidents. The tools offered may provide a path for safety practitioners to reach a disengaged generation of workers to build a cohesive and inclusive conversation around ways to keep people safe at work.

Keywords: social media, workplace safety, communication strategies, young workers

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Authors: Swanand Pathak, Kiran R. Giri, Reena R. Giri, Kamlesh Palandurkar, Sangita Totade, Rajesh Jha, S. S. Patel

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Background: Population burden, illiteracy, availability of few doctors for larger group of population leads to many unanswered questions left in a patient’s mind. Incomplete information results into noncompliance, therapeutic failure, and adverse drug reactions (ADR). It is very important to establish a system which will provide noncommercial, independent, unbiased source of medicine information. Medicines Info OPD is a concept and step towards safe and appropriate use of medicines. Objective: (1) to assess the present status of knowledge about the medicines in the patients and its correlation with education; (2) to assess the medicine information dispensing modalities, their use and sufficiency from the patients view point; (3) to assess the overall need for Medicines Information OPD in present scenario. Materials and Methods: A pre-validated questionnaire based study was conducted amongst 500 patients of tertiary health care hospital. The questionnaire consisted of specific questions regarding understanding of prescription, knowledge about adverse drug reaction, view about self-medication and opinion regarding the need of Medicines Info OPD. Results: Significantly large proportion of patients opined that doctors do not have sufficient time in current Indian healthcare to explain the prescription and they are not aware of adverse drug reactions, expiry date or use the package inserts etc. Conclusion: Clinically relevant, up to date, user specific, independent, objective and unbiased Medicines Info OPD is essential for appropriate drug use and can help in a big way to common public to address many problems faced by them.

Keywords: information, prescription, unbiased, clinically relevant

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Authors: Giancarlo La Marca, Engy Shokry, Fabio Villanelli

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Epilepsy is one of the most common neurological disorders, with an estimated prevalence of 50 million people worldwide. Twenty five percent of the epilepsy population is represented in children under the age of 15 years. For antiepileptic drugs (AED), there is a poor correlation between plasma concentration and dose especially in children. This was attributed to greater pharmacokinetic variability than adults. Hence, therapeutic drug monitoring (TDM) is recommended in controlling toxicity while drug exposure is maintained. Carbamazepine (CBZ) is a first-line AED and the drug of first choice in trigeminal neuralgia. CBZ is metabolised in the liver into carbamazepine-10,11-epoxide (CBZE), its major metabolite which is equipotent. This develops the need for an assay able to monitor the levels of both CBZ and CBZE. The aim of the present study was to develop and validate a LC-MS/MS method for simultaneous quantification of CBZ and CBZE in dried blood spots (DBS). DBS technique overcomes many logistical problems, ethical issues and technical challenges faced by classical plasma sampling. LC-MS/MS has been regarded as superior technique over immunoassays and HPLC/UV methods owing to its better specificity and sensitivity, lack of interference or matrix effects. Our method combines advantages of DBS technique and LC-MS/MS in clinical practice. The extraction process was done using methanol-water-formic acid (80:20:0.1, v/v/v). The chromatographic elution was achieved by using a linear gradient with a mobile phase consisting of acetonitrile-water-0.1% formic acid at a flow rate of 0.50 mL/min. The method was linear over the range 1-40 mg/L and 0.25-20 mg/L for CBZ and CBZE respectively. The limit of quantification was 1.00 mg/L and 0.25 mg/L for CBZ and CBZE, respectively. Intra-day and inter-day assay precisions were found to be less than 6.5% and 11.8%. An evaluation of DBS technique was performed, including effect of extraction solvent, spot homogeneity and stability in DBS. Results from a comparison with the plasma assay are also presented. The novelty of the present work lies in being the first to quantify CBZ and its metabolite from only one 3.2 mm DBS disc finger-prick sample (3.3-3.4 µl blood) by LC-MS/MS in a 10 min. chromatographic run.

Keywords: carbamazepine, carbamazepine-10, 11-epoxide, dried blood spots, LC-MS/MS, therapeutic drug monitoring

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Authors: Young-Hun Lee, Tae-Gwan Kim, Jong-Kyu Kim, Young-Chul Park

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In this study, Spring safety valve Heat - structure coupled analysis was carried out. Full analysis procedure and performing thermal analysis at a maximum temperature, them to the results obtained through to give an additional load and the pressure on the valve interior, and Disc holder Heat-Coupled structure Analysis was carried out. Modeled using a 3D design program Solidworks, For the modeling of the safety valve was used 3D finite element analysis program ANSYS. The final result to be obtained through the Analysis examined the stability of the maximum displacement and the maximum stress to the valve internal components occurring in the high-pressure conditions.

Keywords: finite element method, spring safety valve, gap, stress, strain, deformation

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Authors: Rodrigo Aguiar, Adelino Ferreira

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Road traffic accidents are the leading cause of unnatural death and injuries worldwide, representing a significant problem of road safety. In this context, the use of artificial intelligence with advanced machine learning techniques has gained prominence as a promising approach to predict traffic accidents. This article investigates the application of machine learning algorithms to develop traffic accident frequency prediction models. Models are evaluated based on performance metrics, making it possible to do a comparative analysis with traditional prediction approaches. The results suggest that machine learning can provide a powerful tool for accident prediction, which will contribute to making more informed decisions regarding road safety.

Keywords: machine learning, artificial intelligence, frequency of accidents, road safety

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Authors: Subrata Kar, Banani Kundu, Papiya Nandy, Ruma Basu, Sukhen Das

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Natural montmorilollite clay is a common ingredient in pharmaceutical products, both as excipients and active support; hence considered as suitable candidate for Drug Delivery System. In this work, cationic detergent CTAB is used to increase the interlayer spacing of Na+-Montmoriollite clay to intercalate curcumin and methotrexate. Methotrexate is a folic acid antagonist, anti-proliferative and immunosuppressive agent; while curcumin is a bioactive constituent of rhizomes of Curcuma longa, possessing remarkable chemo-preventive and anti-inflammatory properties. The resultant inorganic-organic hybrids are characterized by X-ray diffraction (XRD), Infrared spectroscopy (FTIR) and Thermo Gravimetric Analysis (TGA) to confirm successful intercalation of curcumin and Methotrexate within clay layers. Pharmaceutical investigation of the hybrids is explored by studying the drug loading (%), encapsulation efficiency and release kinetics. Finally in-vitro studies are performed using cancer cells to find the effect of released curcumin to improve the sensitivity of clay bound methotrexate to ameliorate cell death compared to their effectiveness when used without the inorganic aluminosilicate vehicle.

Keywords: montmorillonite, methotrexate, curcumin, loading efficiency, release kinetics, anticancer activity

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Authors: Sarah P. Wuebbolt, Ashlee N. Sawyer-Mays

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Non-medical prescription and other drug (NMPOD) use has been a significant public health issue for the last few decades, with problematic use increasing among university students more recently. The current study focused on associations between NMPOD use and mental health, well-being, and world beliefs among young adults. Young adults (N=513) completed online questionnaires assessing stress, demographic characteristics, self-esteem, NMPOD use, coping mechanisms, and anxiety. A substantial portion of participants reported using cannabis (48.5%, n=249), while smaller portions of participants reported using stimulants (26.7%, n = 137), sedatives (17.2%, n=88), opioids (10.8%, n=55), and hallucinogens (14.4%, n=74). Five hierarchical logistic regressions were performed to determine the independent relationships between mental health, well-being, and world belief factors and NMPOD use for the five classes of substances. After controlling for demographic factors (age, gender, race/ethnicity, sexual orientation, and religious affiliation), depression was associated with increased non-medical stimulant, opioid, and cannabis use; coping self-efficacy was associated with increased hallucinogen use, and attendance of worship services was associated with decreased non-medical cannabis and hallucinogen use. Results suggest that depression was strongly associated with non-medical stimulant, opioid, and cannabis use, and attendance of worship services was protective against cannabis and hallucinogen use. To the best of our knowledge, this is one of the first studies to investigate the relationships between mental health, well-being, world beliefs, and NMPOD use among young adults. The present study illuminates future targets for intervention, such as increased access to mental health diagnosis and treatment and the exploration of the roles of religion and shared community in the prevention of drug use among young adults.

Keywords: cannabis, mental health, non-medical prescription and other drug use, world beliefs

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Authors: Krutika K. Sawant, Anil Solanki

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The present study deals with the preparation and optimization of ethyl cellulose-containing disopyramide phosphate loaded microspheres using solvent evaporation technique. A central composite design consisting of a two-level full factorial design superimposed on a star design was employed for optimizing the preparation microspheres. The drug:polymer ratio (X1) and speed of the stirrer (X2) were chosen as the independent variables. The cumulative release of the drug at a different time (2, 6, 10, 14, and 18 hr) was selected as the dependent variable. An optimum polynomial equation was generated for the prediction of the response variable at time 10 hr. Based on the results of multiple linear regression analysis and F statistics, it was concluded that sustained action can be obtained when X1 and X2 are kept at high levels. The X1X2 interaction was found to be statistically significant. The drug release pattern fitted the Higuchi model well. The data of a selected batch were subjected to an optimization study using Box-Behnken design, and an optimal formulation was fabricated. Good agreement was observed between the predicted and the observed dissolution profiles of the optimal formulation.

Keywords: disopyramide phosphate, ethyl cellulose, microspheres, controlled release, Box-Behnken design, factorial design

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Authors: Chee Wee Gan, Anthony Herr Cheun Ng, Yee Shan Wong, Subbu Venkatraman, Lynne Hsueh Yee Lim

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Otitis media with effusion (OME) is the leading cause of hearing loss in children worldwide. Surgery to insert grommet tube into the eardrum is usually indicated for OME unresponsive to antimicrobial therapy. It is the most common surgery for children. However, current commercially available grommet tubes are non-bioresorbable, not drug-treated, with unpredictable duration of retention on the eardrum to ventilate middle ear. Their functionality is impaired when clogged or chronically infected, requiring additional surgery to remove/reinsert grommet tubes. We envisaged that a novel fully bioresorbable grommet tube with sustained antibiotic release technology could address these drawbacks. In this study, drug-loaded bioresorbable poly(L-lactide-co-ε-caprolactone)(PLC) copolymer grommet tubes were fabricated by microinjection moulding technique. In vitro drug release and degradation model of PLC tubes were studied. Antibacterial property was evaluated by incubating PLC tubes with P. aeruginosa broth. Surface morphology was analyzed using scanning electron microscopy. A preliminary animal study was conducted using guinea pigs as an in vivo model to evaluate PLC tubes with and without drug, with commercial Mini Shah grommet tube as comparison. Our in vitro data showed sustained drug release over 3 months. All PLC tubes revealed exponential degradation profiles over time. Modeling predicted loss of tube functionality in water to be approximately 14 weeks and 17 weeks for PLC with and without drug, respectively. Generally, PLC tubes had less bacteria adherence, which were attributed to the much smoother tube surfaces compared to Mini Shah. Antibiotic from PLC tube further made bacteria adherence on surface negligible. They showed neither inflammation nor otorrhea after 18 weeks post-insertion in the eardrums of guinea pigs, but had demonstrated severe degree of bioresorption. Histology confirmed the new PLC tubes were biocompatible. Analyses on the PLC tubes in the eardrums showed bioresorption profiles close to our in vitro degradation models. The bioresorbable antibiotic-loaded grommet tubes showed good predictability in functionality. The smooth surface and sustained release technology reduced the risk of tube infection. Tube functional duration of 18 weeks allowed sufficient ventilation period to treat OME. Our ongoing studies include modifying the surface properties with protein coating, optimizing the drug dosage in the tubes to enhance their performances, evaluating their functional outcome on hearing after full resoption of grommet tube and healing of eardrums, and developing animal model with OME to further validate our in vitro models.

Keywords: bioresorbable polymer, drug release, grommet tube, guinea pigs, otitis media with effusion

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Authors: Mani Mofidi, Neda Valizadeh, Ali Hashemaghaee, Mona Hashemaghaee, Soudabeh Shafiee Ardestani

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Background: Acute pain and its management remained the most complaint of emergency service admission. Diagnostic and therapeutic procedures add to patients’ pain. Diminishing the pain increases the quality of patient’s feeling and improves the patient-physician relationship. Aim: The aim of this study was to evaluate the outcomes and side effects of opioid administration in emergency patients. Material and Methods: patients admitted to ward II emergency service of Imam Khomeini hospital, who received one of the opioids: morphine, pethidine, methadone or fentanyl as an analgesic were evaluated. Their vital signs and general condition were examined before and after drug injection. Also, patient’s pain experience were recorded as numerical rating score (NRS) before and after analgesic administration. Results: 268 patients were studied. 34 patients were addicted to opioid drugs. Morphine had the highest rate of prescription (86.2%), followed by pethidine (8.5%), methadone (3.3%) and fentanyl (1.68). While initial NRS did not show significant difference between addicted patients and non-addicted ones, NRS decline and its score after drug injection were significantly lower in addicted patients. All patients had slight but statistically significant lower respiratory rate, heart rate, blood pressure and O2 saturation. There was no significant difference between different kind of opioid prescription and its outcomes or side effects. Conclusion: Pain management should be always in physicians’ mind during emergency admissions. It should not be assumed that an addicted patient complaining of pain is malingering to receive drug. Titration of drug and close monitoring must be in the curriculum to prevent any hazardous side effects.

Keywords: numerical rating score, opioid, pain, emergency department

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Authors: Mensah-Akoto Julius, Kenichi Matsui

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This paper examines the impact of COVID-19 on waste management workers in Ghana. A questionnaire survey was conducted among 60 waste management workers in Accra metropolis, the capital region of Ghana, to understand the impact of the COVID-19 pandemic on waste generation, workers’ safety in collecting solid waste, and service delivery. To find out correlations between the pandemic and safety of waste management workers, a regression analysis was used. Regarding waste generation, the results show the pandemic led to the highest annual per capita solid waste generation, or 3,390 tons, in 2020. Regarding the safety of workers, the regression analysis shows a significant and inverse association between COVID-19 and waste management services. This means that contaminated wastes may infect field workers with COVID-19 due to their direct exposure. A rise in new infection cases would have a negative impact on the safety and service delivery of the workers. The result also shows that an increase in economic activities negatively impacts waste management workers. The analysis, however, finds no statistical relationship between workers’ service deliveries and employees’ salaries. The study then discusses how municipal waste management authorities can ensure safe and effective waste collection during the pandemic.

Keywords: Covid-19, waste management worker, waste collection, Ghana

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Authors: Prasanna Kumar Khaund, Sukanya Talukdar

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A concrete gravity dam is a major hydraulic structure and it is very essential to consider the earthquake forces, to get a proper design base width, so that the entire weight of the dam resists the overturning moment due to earthquake and other forces. The main objective of this study is to obtain the design base width of a dam for different seismic conditions by varying the earthquake coefficients in both vertical and horizontal directions. This shall be done by equating the factor of safety against overturning, factor of safety against sliding and factor of safety against shear friction factor for a dam with their limiting values, under both tail water and no tail water condition. The shape of the Mettur dam in India is considered for the study. The study has been done taking a constant head of water at the reservoir, which is the maximum reservoir water level and a constant height of tail water. Using linear approximation method of Newton Raphson, the obtained equations against different factors of safety under different earthquake conditions are solved using a programme in C++ to get different values of base width of dam for varying earthquake conditions.

Keywords: design base width, horizontal earthquake coefficient, tail water, vertical earthquake coefficient

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Authors: Seyed Abbas Tabatabaei, Marjan Naderan Tahan, Arman Kadkhodai

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An efficient optimization approach, called feasible gate (FG), is developed to enhance the computation efficiency and solution quality of the previously developed highway alignment optimization (HAO) model. This approach seeks to realistically represent various user preferences and environmentally sensitive areas and consider them along with geometric design constraints in the optimization process. This is done by avoiding the generation of infeasible solutions that violate various constraints and thus focusing the search on the feasible solutions. The proposed method is simple, but improves significantly the model’s computation time and solution quality. On the other, highway alignment optimization through Feasible Gates, eventuates only economic model by considering minimum design constrains includes minimum reduce of circular curves, minimum length of vertical curves and road maximum gradient. This modelling can reduce passenger comfort and road safety. In most of highway optimization models, by adding penalty function for each constraint, final result handles to satisfy minimum constraint. In this paper, we want to propose a safety-function solution by introducing gift function.

Keywords: safety, highway geometry, optimization, alignment

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Authors: Gagan Dhawan

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Mycobacterium tuberculosis was described as ‘captain of death’ with an inherent property of multiple drug resistance majorly caused by the competent mechanism of efflux pumps. In this study, various open source tools combining chemo-informatics with bioinformatics were used for efficient in-silico drug designing. The efflux pump, Rv1218c, belonging to the ABC transporter superfamily, which is predicted to be a tetronasin-transporter in M. tuberculosis was targeted. Recent studies have shown that Rv1218c forms a complex with two more efflux pumps (Rv1219c and Rv1217c) to provide multidrug resistance to the bacterium. The 3D structure of the protein was modeled (as the structure was unavailable in the previously collected databases on this gene). The TMHMM analysis of this protein in TubercuList has shown that this protein is present in the outer membrane of the bacterium. Virtual screening of compounds from various publically available chemical libraries was performed on the M. tuberculosis protein using various open source tools. These ligands were further assessed where various physicochemical properties were evaluated and analyzed. On comparison of different physicochemical properties, toxicity and docking, the ligand 2-(hydroxymethyl)-6-[4, 5, 6-trihydroxy-2-(hydroxymethyl) tetrahydropyran-3-yl] oxy-tetrahydropyran-3, 4, 5-triol was found to be best suited for further studies.

Keywords: drug resistance, efflux pump, molecular docking, virtual screening

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Authors: Syed Asif Hassan, Tabrej Khan

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Multiple sclerosis (MS) is a chronic demyelinating autoimmune disorder, of the central nervous system (CNS). In the present scenario, the current therapies either do not halt the progression of the disease or have side effects which limit the usage of current Disease Modifying Therapies (DMTs) for a longer period of time. Therefore, keeping the current treatment failure schema, we are focusing on screening novel analogues of the available DMTs that specifically bind and inhibit the Sphingosine1-phosphate receptor1 (S1PR1) thereby hindering the lymphocyte propagation toward CNS. The novel drug-like analogs molecule will decrease the frequency of relapses (recurrence of the symptoms associated with MS) with higher efficacy and lower toxicity to human system. In this study, an integrated approach involving ligand-based virtual screening protocol (Ultrafast Shape Recognition with CREDO Atom Types (USRCAT)) to identify the non-toxic drug like analogs of the approved DMTs were employed. The potency of the drug-like analog molecules to cross the Blood Brain Barrier (BBB) was estimated. Besides, molecular docking and simulation using Auto Dock Vina 1.1.2 and GOLD 3.01 were performed using the X-ray crystal structure of Mtb LprG protein to calculate the affinity and specificity of the analogs with the given LprG protein. The docking results were further confirmed by DSX (DrugScore eXtented), a robust program to evaluate the binding energy of ligands bound to the ligand binding domain of the Mtb LprG lipoprotein. The ligand, which has a higher hypothetical affinity, also has greater negative value. Further, the non-specific ligands were screened out using the structural filter proposed by Baell and Holloway. Based on the USRCAT, Lipinski’s values, toxicity and BBB analysis, the drug-like analogs of fingolimod and BG-12 showed that RTL and CHEMBL1771640, respectively are non-toxic and permeable to BBB. The successful docking and DSX analysis showed that RTL and CHEMBL1771640 could bind to the binding pocket of S1PR1 receptor protein of human with greater affinity than as compared to their parent compound (Fingolimod). In this study, we also found that all the drug-like analogs of the standard MS drugs passed the Bell and Holloway filter.

Keywords: antagonist, binding affinity, chemotherapeutics, drug-like, multiple sclerosis, S1PR1 receptor protein

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Authors: Özlem Turan, Şule Turhan

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About 1 billion people in the world are suffering from hunger. Approximately 1.3 billion tons of produced food is wasted each year as well. While the waste of industrialized countries is 670 million tons per year, the waste per year in developing countries is estimated as 630 million tons. When evaluated in this respect, the importance of sustainability and food security can be seen clearly. Food safety is defined as taking the necessary measures and eliminating all risk arising from food. The goal of sustainable food security is, protection of consumer health, development of safe food and beverages trade nationally and internationally and to ensure reliable fair trade schemes. In this study, this study will focus on sustainable food systems and food security, by examining the food wastage and losses from environmental and economic point of views and the precautions that need to be taken will be discussed.

Keywords: food, food safety, food systems, sustainability

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Authors: Issam Alnader, Aboubaker Lasebae, Rand Raheem

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Wireless sensor networks (WSNs) are distributed network systems used in a wide range of applications, including safety-critical systems. The latter provide critical services, often concerned with human life or assets. Therefore, ensuring the dependability requirements of Safety critical systems is of paramount importance. The purpose of this paper is to utilize the Hidden Markov Model (HMM) to elongate the service availability of WSNs by increasing the time it takes a node to become obsolete via optimal load balancing. We propose an HMM algorithm that, given a WSN, analyses and predicts undesirable situations, notably, nodes dying unexpectedly or prematurely. We apply this technique to improve on C. Lius’ algorithm, a scheduling-based algorithm which has served to improve the lifetime of WSNs. Our experiments show that our HMM technique improves the lifetime of the network, achieved by detecting nodes that die early and rebalancing their load. Our technique can also be used for diagnosis and provide maintenance warnings to WSN system administrators. Finally, our technique can be used to improve algorithms other than C. Liu’s.

Keywords: wireless sensor networks, IoT, dependability of safety WSNs, energy conservation, sleep awake schedule

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Authors: Feras Darwish Elhajji, Alberto Berardi, Manal Ayyash, Iman Basheti

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The concept of the use of probiotics for humans now has been known for decades however, their intake by the Jordanian population seems to be less common when compared to population in the developed countries. Community pharmacy is the main supplier of probiotics, however, after conducting an extensive literature review, not any published research article could be found talking about the role, knowledge, and practice of the pharmacists in the area of probiotics. The main aim of this study was to evaluate the level of knowledge about probiotics and their dispensing practice in community pharmacies in Jordan. Community pharmacy staff (pharmacists and technicians) in Amman and north of Jordan were randomly selected to complete an anonymous questionnaire that had been pre-tested and validated. Ethical approval was obtained from the university ethics committee. The questionnaire included the following sections: demographics, knowledge and perceptions about probiotics, and role of the pharmacist Pharmacists and technicians were visited and interviewed in 281 community pharmacies. Asking about probiotics, 90.4% of them said that they know what probiotics are, although only 29.5% agreed that pharmacy staff in Jordan have good knowledge about probiotics, and 88.3% agreed that pharmacy staff in Jordan need more training and knowledge about probiotics. Variables that were significantly related to knowledge about probiotics were being a pharmacist (ρ= 0.012), area of the community pharmacy (ρ= 0.019), and female staff (ρ= 0.031) after conducting logistic regression statistical analysis. More than two-thirds of the participants thought that probiotics are classified as dietary supplements by Jordan Food and Drug Administration (JFDA). Of those who knew probiotics, the majority of them – 76.8% and 91.7% – agreed that probiotics are effective and safe, respectively. Believing in efficacy of the probiotics was significantly associated with answering their use to be with or after antibiotic administration and to increase normal flora gut population (ρ= 0.007). Efficacy was also significantly associated with recommending probiotics to consumers by the pharmacist (ρ< 0.001) and by the doctor (ρ= 0.041). At the same time, the concept of safety was mainly associated with their use for flatulence and gases (ρ= 0.048). Level of knowledge about probiotics and their uses, efficacy and safety amongst community pharmacy staff in Jordan is found to be good. However, this level can be raised in the future, especially knowledge about uses of probiotics.

Keywords: community pharmacy, Jordan, prebiotics, probiotics

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Authors: Reynaldo Esquivel, Pedro Hernandez, Aaron Martinez-Higareda, Sergio Tena-Cano, Enrique Alvarez-Ramos, Armando Lucero-Acuna

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Stimuli-responsive nanomaterials play an essential role in loading, transporting and well-distribution of anti-cancer compounds in the cellular surroundings. The outstanding properties as the Lower Critical Solution Temperature (LCST), hydrolytic cleavage and protonation/deprotonation cycle, govern the release and delivery mechanisms of payloads. In this contribution, we experimentally determine the load efficiency and release of antineoplastic Vincristine Sulfate into PNIPAM-Interpenetrated-Chitosan (PIntC) nanoparticles. Structural analysis was performed by Fourier Transform Infrared Spectroscopy (FT-IR) and Proton Nuclear Magnetic Resonance (1HNMR). ζ-Potential (ζ) and Hydrodynamic diameter (DH) measurements were monitored by Electrophoretic Mobility (EM) and Dynamic Light scattering (DLS) respectively. Mathematical analysis of the release pharmacokinetics reveals a three-phase model above LCST, while a monophasic of Vincristine release model was observed at 32 °C. Cytotoxic essays reveal a noticeable enhancement of Vincristine effectiveness at low drug concentration on HeLa cervix cancer and MDA-MB-231 breast cancer.

Keywords: nanoparticles, vincristine, drug delivery, PNIPAM

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Authors: Akinsola Oluwatosin, Udofia Samuel, Odofin Mayowa

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The study is aimed at assessing the Geographic Information System (GIS)-based spatial analysis of Survival Pattern and Treatment Outcomes of Multi-Drug Resistant Tuberculosis (MDR-TB) cases for Lagos, Nigeria, with an objective to inform priority areas for public health planning and resource allocation. Multi-drug resistant tuberculosis (MDR-TB) develops due to problems such as irregular drug supply, poor drug quality, inappropriate prescription, and poor adherence to treatment. The shapefile(s) for this study were already georeferenced to Minna datum. The patient’s information was acquired on MS Excel and later converted to . CSV file for easy processing to ArcMap from various hospitals. To superimpose the patient’s information the spatial data, the addresses was geocoded to generate the longitude and latitude of the patients. The database was used for the SQL query to the various pattern of the treatment. To show the pattern of disease spread, spatial autocorrelation analysis was used. The result was displayed in a graphical format showing the areas of dispersing, random and clustered of patients in the study area. Hot and cold spot analysis was analyzed to show high-density areas. The distance between these patients and the closest health facility was examined using the buffer analysis. The result shows that 22% of the points were successfully matched, while 15% were tied. However, the result table shows that a greater percentage of it was unmatched; this is evident in the fact that most of the streets within the State are unnamed, and then again, most of the patients are likely to supply the wrong addresses. MDR-TB patients of all age groups are concentrated within Lagos-Mainland, Shomolu, Mushin, Surulere, Oshodi-Isolo, and Ifelodun LGAs. MDR-TB patients between the age group of 30-47 years had the highest number and were identified to be about 184 in number. The outcome of patients on ART treatment revealed that a high number of patients (300) were not ART treatment while a paltry 45 patients were on ART treatment. The result shows the Z-score of the distribution is greater than 1 (>2.58), which means that the distribution is highly clustered at a significance level of 0.01.

Keywords: tuberculosis, patients, treatment, GIS, MDR-TB

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Authors: Anna Bjällmark, Victoria Persson, Bodil Karlsson, May Bazzi

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Introduction: Interventional radiology (IR) is a continuously growing discipline that allows minimally invasive treatments of various medical conditions. The IR environment is, in several ways, comparable to the complex and accident-prone operation room (OR) environment. This implies that the IR environment may also be associated with various types of risks related to the work process and communication in the team. Patient safety is a central aspect of healthcare and involves the prevention and reduction of adverse events related to patient care. To maintain patient safety, it is crucial to build a safety culture where the staff are encouraged to report events and incidents that may have affected patient safety. It is also important to continuously evaluate the staff´s attitudes to patient safety. Despite the increasing number of IR procedures, research on the staff´s view regarding patients is lacking. Therefore, the main aim of the study was to describe and compare the IR team members' attitudes to patient safety. The secondary aim was to evaluate whether the WHO safety checklist was routinely used for IR procedures. Methods: An electronic survey was distributed to 25 interventional units in Sweden. The target population was the staff working in the IR team, i.e., physicians, radiographers, nurses, and assistant nurses. A modified version of the Safety Attitudes Questionnaire (SAQ) was used. Responses from 19 of 25 IR units (44 radiographers, 18 physicians, 5 assistant nurses, and 1 nurse) were received. The respondents rated their level of agreement for 27 items related to safety culture on a five-point Likert scale ranging from “Disagree strongly” to “Agree strongly.” Data were analyzed statistically using SPSS. The percentage of positive responses (PPR) was calculated by taking the percentage of respondents who got a scale score of 75 or higher. The respondents rated which corresponded to response options “Agree slightly” or “Agree strongly”. Thus, average scores ≥ 75% were classified as “positive” and average scores < 75% were classified as “non-positive”. Findings: The results indicated that the IR team had the highest factor scores and the highest percentages of positive responses in relation to job satisfaction (90/94%), followed by teamwork climate (85/92%). In contrast, stress recognition received the lowest ratings (54/25%). Attitudes related to these factors were relatively consistent between different professions, with only a few significant differences noted (Factor score: p=0.039 for job satisfaction, p=0.050 for working conditions. Percentage of positive responses: p=0.027 for perception of management). Radiographers tended to report slightly lower values compared to other professions for these factors (p<0.05). The respondents reported that the WHO safety checklist was not routinely used at their IR unit but acknowledged its importance for patient safety. Conclusion: This study reported high scores concerning job satisfaction and teamwork climate but lower scores concerning perception of management and stress recognition indicating that the latter are areas of improvement. Attitudes remained relatively consistent among the professions, but the radiographers reported slightly lower values in terms of job satisfaction and perception of the management. The WHO safety checklist was considered important for patient safety.

Keywords: interventional radiology, patient safety, safety attitudes questionnaire, WHO safety checklist

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Authors: Odd Ivar Haugen

Abstract:

This paper explores the relationship between assurance, risk, and risk management in the context of complex safety-related systems. It introduces a nuanced understanding of assurance and argues that the foundation for grounds for justified confidence in claims made about a complex system is related to the system behaviour. It emphasises the importance of knowledge as the cornerstone of assurance. The paper addresses the challenges of epistemic and aleatory uncertainties inherent in safety-critical systems. A systems approach is proposed to model emergent properties and complexity using the composition, environment, structure, mechanisms (CESM) metamodel, offering a structured framework for analysing system behaviour. The interplay between assurance and risk management is conceptualised through two models: the domain model and the control model. Assurance and risk management are mutually dependent on each other to reduce uncertainty and control risk levels. This work highlights the dual roles of assurance in risk management, acting as an epistemic actuator on the one side and providing feedback about the strength of the justification on the other. Assurance and risk management have inseparable roles in ensuring safety in complex systems.

Keywords: assurance, CESM metamodel, confidence, emergent properties, knowledge, objectivity, risk, system behaviour, system safety

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Authors: Ismail Muratoglu, Ahmet Meyveci, Abdurrahman Tuncer, Erkan Demirci

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This study is dedicated to the analysis of the problems of occupational safety in Turkey, Italy and Poland. The need analysis was applied to three different countries which are Turkey; 4, Poland; 1, Italy; 1 state. The number of the subjects is 891 in Turkey. The number of the subjects is 26 in Italy and the number of the subjects is 19 in Poland. The total number of samples of study is 936. Four different forms (Job Security Experts Form, Student Form, Teacher Form and Company Form) were applied. Results of experts of job security forms are rate of 7.1%. Then, the students’ forms are rate of 34.3%, teacher or instructor forms are rate of 9.9%. The last corporation forms are rate of 48.7%.

Keywords: Europe, need analysis, occupational safety, Turkey, vocational education

Procedia PDF Downloads 432