Search results for: drug errors

Authors: Heba A. Hazzah, Ragwa M. Farid, Maha M. A. Nasra, Mennatallah Zakria, Magda A. El Massik, Ossama Y. Abdallah

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Introduction: Curcumin (Cur) is a polyphenol derived from the herbal remedy and dietary spice turmeric. It possesses diverse anti-inflammatory and anti-cancer properties following oral or topical administration. The buccal delivery of curcumin can be useful for both systemic and local disease treatments such as gingivitis, periodontal diseases, oral carcinomas, and precancerous oral lesions. Despite of its high activity, it suffers a limited application due to its low oral bioavailability, poor aqueous solubility, and instability. Aim: Preparation and characterization of curcumin solid lipid nanoparticles with a high loading capacity into a mucoadhesive gel for buccal application. Methodology: Curcumin was formulated as nanoparticles using different lipids, namely Gelucire 39/01, Gelucire 50/13, Precirol, Compritol, and Polaxomer 407 as a surfactant. The SLN were dispersed in a mucoadhesive gel matrix to be applied to the buccal mucosa. All formulations were evaluated for their content, entrapment efficiency, particle size, in vitro drug dialysis, ex vivo mucoadhesion test, and ex vivo permeation study using chicken buccal mucosa. Clinical evaluation was conducted on 15 cases suffering oral erythroplakia and erosive lichen planus. Results: The results showed high entrapment efficiency reaching almost 90 % using Gelucire 50, the loaded gel with Cur-SLN showed good adhesion property and 25 minutes in vivo residence time. In addition to stability enhancement for the Cur powder. All formulae did not show any drug permeated however, a significant amount of Cur was retained within the mucosal tissue. Pain and lesion sizes were significantly reduced upon topical treatment. Complete healing was observed after 6 weeks of treatment. Conclusion: These results open a room for the pharmaceutical technology to optimize the use of this golden magical powder to get the best out of it. In addition, the lack of local anti-inflammatory compounds with reduced side effects intensifies the importance of studying natural products for this purpose.

Keywords: curcumin, erythroplakia, mucoadhesive, pain, solid lipid nanoparticles

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Authors: Shorena Sadzaglishvili, Teona Gotsiridze, Ketevan Lekishvili, Darejan Javakhishvili, Alida Bouris

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Globally, adolescents and young people experience high levels of HIV vulnerability and risk. Estimates suggest that AIDS-related deaths among young people are increasing, suggesting poor prioritization of adolescents in national plans for HIV testing and treatment services. HIV/AIDS is currently the sixth leading cause of death in people aged 10-24 years. Among young people, street connected youth are clearly distinguished as being among the most at risk for HIV infection. The present study recognizes the urgent need to scale up effective HIV responses that are tailored to the unique needs of street connected youth for the global HIV agenda and especially, the former Soviet country - Georgia, where 'street kids' are a new phenomenon and estimated to be about 2,500. During two months trained interviewers conducted individual semi-structured qualitative interviews with 22 key informants from the local governmental and nongovernmental service organizations, including psychologists, social workers, peer educators, mobile health workers, and managers. Informants discussed social network characteristics influencing street connected youth’s sexual risk behaviors. Data were analyzed using Dedoose. It was revealed that there are three types of homogeneous networks of street-connected youth aged 10-19 based on ethnical background: (1) Georgians; (2) migrant kids of Azeri-Kurdish origin, and (3) local Roma-Moldavian kids. These networks are distinguished with various HIV risk through both risky sexual and drug-related behaviors. In addition, there are several cases of HIV infection identified through reactive social services. Street connected youth do not have basic information about the HIV related sexual, alcohol and drug behaviors nor there are any systematic programs providing HIV testing and consultation for reducing the vulnerability of HIV infection. There is a need to systematically examine street-connected youth risk-taking behaviors by applying an integrated, multilevel framework to a population at great risk of HIV. Acknowledgment: This work was supported by Shota Rustaveli National Science Foundation of Georgia (SRNSFG) [#FR 17_31], Ilia State University.

Keywords: street connected youth, social networks, HIV/AIDS, HIV testing

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Authors: Mansour Al Qubeissi, Sergei S. Sazhin, Cyril Crua, Morgan R. Heikal

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This paper presents the application of the Discrete Component Model for heating and evaporation to multi-component biodiesel fuel droplets in direct injection internal combustion engines. This model takes into account the effects of temperature gradient, recirculation and species diffusion inside droplets. A distinctive feature of the model used in the analysis is that it is based on the analytical solutions to the temperature and species diffusion equations inside the droplets. Nineteen types of biodiesel fuels are considered. It is shown that a simplistic model, based on the approximation of biodiesel fuel by a single component or ignoring the diffusion of components of biodiesel fuel, leads to noticeable errors in predicted droplet evaporation time and time evolution of droplet surface temperature and radius.

Keywords: heat/mass transfer, biodiesel, multi-component fuel, droplet

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Authors: M. Mousavi-Daramoroudi, H. Yousefnia, F. Abbasi-Davani, S. Zolghadri

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In this study, ¹⁷⁷Lu-DOTATOC was prepared under optimized conditions (radiochemical purity: > 99%, radionuclidic purity: > 99%). The percentage of injected dose per gram (%ID/g) was calculated for organs up to 168 h post injection. Compartmental model was applied to mathematical description of the drug behaviour in tissue at different times. The biodistribution data showed the significant excretion of the radioactivity from the kidneys. The adrenal and pancreas, as major expression sites for somatostatin receptor (SSTR), had significant uptake. A pharmacokinetic model of ¹⁷⁷Lu-DOTATOC was presented by compartmental analysis which demonstrates the behavior of the complex.

Keywords: biodistribution, compartmental modeling, ¹⁷⁷Lu, Octreotide

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Authors: Khaled ElEbyary, Ramy Shabara

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L2 research has generally acknowledged the role of noticing in language learning. The role of teacher feedback is to trigger learners’ noticing of errors and direct the writing process. Recently L2 learners are seemingly using computerized applications which provide corrective feedback (CF) at different stages of writing (i.e., during and after writing). This study aimed principally to answer the question, “Is noticing likely to be maximized when feedback on erroneous output is electronically provided either during or after the composing stage, or does teacher annotated feedback have a stronger effect?”. Seventy-five participants were randomly distributed into four groups representing four conditions. These include receiving automated feedback at the composing stage, automated feedback after writing, teacher feedback, and no feedback. Findings demonstrate the impact of CF on writing and the intensity of noticing certain language areas at different writing stages and from different feedback sources.

Keywords: written corrective feedback, error correction, noticing, automated written corrective feedback, L2 acquisition

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Authors: Pouya Kaafi, Gholamreza Ghodrati Amiri

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Abnormal loads due to natural events, implementation errors and some other issues can lead to occurrence of progressive collapse in structures. Most of the past researches consist of 2- Dimensional (2D) models of steel frames without consideration of the floor system effects, which reduces the accuracy of the modeling. While employing a 3-Dimensional (3D) model and modeling the concrete slab system for the floors have a crucial role in the progressive collapse evaluation. In this research, a 3D finite element model of a 5-story steel building is modeled by the ABAQUS software once with modeling the slabs, and the next time without considering them. Then, the progressive collapse potential is evaluated. The results of the analyses indicate that the lack of the consideration of the slabs during the analyses, can lead to inaccuracy in assessing the progressive failure potential of the structure.

Keywords: abnormal loads, composite floor system, intermediate steel moment resisting frame system, progressive collapse

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Authors: Arunas Burinskas, Aurelija Burinskiene

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On average, ten percent of drugs - commercial products are not available in pharmacies due to shortage. The shortage event disbalance sales and requires a recovery period, which is too long. Therefore, one of the critical issues that pharmacies do not record potential sales transactions during shortage and recovery periods. The authors suggest estimating outliers during shortage and recovery periods. To shorten the recovery period, the authors suggest using average sales per sales day prediction, which helps to protect the data from being downwards or upwards. Authors use the outlier’s visualization method across different drugs and apply the Grubbs test for significance evaluation. The researched sample is 100 drugs in a one-month time frame. The authors detected that high demand variability products had outliers. Among analyzed drugs, which are commercial products i) High demand variability drugs have a one-week shortage period, and the probability of facing a shortage is equal to 69.23%. ii) Mid demand variability drugs have three days shortage period, and the likelihood to fall into deficit is equal to 34.62%. To avoid shortage events and minimize the recovery period, real data must be set up. Even though there are some outlier detection methods for drug data cleaning, they have not been used for the minimization of recovery period once a shortage has occurred. The authors use Grubbs’ test real-life data cleaning method for outliers’ adjustment. In the paper, the outliers’ adjustment method is applied with a confidence level of 99%. In practice, the Grubbs’ test was used to detect outliers for cancer drugs and reported positive results. The application of the Grubbs’ test is used to detect outliers which exceed boundaries of normal distribution. The result is a probability that indicates the core data of actual sales. The application of the outliers’ test method helps to represent the difference of the mean of the sample and the most extreme data considering the standard deviation. The test detects one outlier at a time with different probabilities from a data set with an assumed normal distribution. Based on approximation data, the authors constructed a framework for scaling potential sales and estimating outliers with Grubbs’ test method. The suggested framework is applicable during the shortage event and recovery periods. The proposed framework has practical value and could be used for the minimization of the recovery period required after the shortage of event occurrence.

Keywords: drugs, Grubbs' test, outlier, shortage event

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Authors: Ade O. Oyewole, Sunday O. Okoh, Ruth O. Ishola, Adenike D. Odusote, Chima C. Igwe, Gloria N. Elemo, Anthony I. Okoh

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Azadirachta indica (Neem tree) also referred to as an all-purpose tree is used in a wide range of medical preparations in tropical and subtropical countries for prevention and management of various livestock, crops products and human diseases. In Nigeria however, the potentials of this plant have not been fully exploited thus it causes an environmental nuisance during the fruiting season. With a rise in the demand for herbal personal care products globally extracts from different parts of the neem plant were used as the bio-active ingredients in the formulation of personal care products. In this study, formulated neem soap, body cream, lotion, toothpaste and shampoo are analyzed to determine their antibacterial, antifungal, and toxicity properties. The efficacies of these products for management of infectious diseases, both oral and dermal, were also investigated in vitro. Oil from the neem seeds obtained using a mechanical press and acetone extracts of both the neem bark and leaves obtained by the maceration method were used in the formulation and production of the neem personal care products. The antimicrobial and toxicity properties of these products were investigated by agar diffusion, and haemolytic methods respectively. The five neem products (NPs) exhibited strong antibacterial activities against four multi–drug resistant pathogenic and three none pathogenic bacterial strains (Escherichia coli (180), Listeria ivanovii, Staphylococcus aureus, Enterobacter cloacae, Vibro spp., Streptococcus uberis, Mycobacterium smegmatis), except the neem lotion with insignificant activity against E. coli and S. aureus. The minimum inhibitory concentration (MIC) range was between 0.20-0.40 mg/ mL. The 5 NPs demonstrated moderate activity against three clinical dermatophytes isolates (Tinea corporis, Tinea capitis, and Tinea cruiz) as well as one fungal strain (Candida albican) with the MIC ranging between 0.30 - 0.50 mg/ mL and 0.550 mg/mL respectively. The soap and shampoo were the most active against test bacteria and fungi. The haemolytic analysis results on the 5 NPs indicated none toxicity at 0.50 mg/ mL in sheep red blood cells (SRBC).

Keywords: antimicrobial, Azadirachta indica, multi–drug resistant pathogenic bacteria, personal care products

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Authors: Agata Migdalska, Joanna Berczynska, Ewa Bieniek, Jacek Sterna

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Muscle relaxation is considered important during general anesthesia for spine stabilization. In a presented case peripherally acting muscle relaxant was applied during general anesthesia for spine stabilization surgery. The patient was a dog, 11-years old, 26 kg, male, mix breed. Spine fracture was situated between Th13-L1-L2, probably due to the car accident. Preanesthetic physical examination revealed no sign underlying health issues. The dog was premedicated with midazolam 0.2 mg IM and butorphanol 2.4 mg IM. General anesthesia was induced with propofol IV. After the induction, the dog was intubated with an endotracheal tube and connected to an open-ended rebreathing system and maintained with the use of inhalation anesthesia with isoflurane in oxygen. 0,5 mg/ kg of rocuronium was given IV. Use of muscle relaxant was accompanied by an assessment of the degree of neuromuscular blockade by peripheral nerve stimulator. Electrodes were attached to the skin overlying at the peroneal nerve at the lateral cranial tibia. Four electrical pulses were applied to the nerve over a 2 second period. When satisfying nerve block was detected dog was prepared for the surgery. No further monitoring of the effectiveness of blockade was performed during surgery. Mechanical ventilation was kept during anesthesia. During surgery dog maintain stable, and no anesthesiological complication occur. Intraoperatively surgeon claimed that neuromuscular blockade results in a better approach to the spine and easier muscle manipulation which was helpful in order to see the fracture and replace bone fragments. Finally, euthanasia was performed intraoperatively as a result of vast myelomalacia process of the spinal cord. This prevented examination of the recovering process. Neuromuscular blocking agents act at the neuromuscular junction to provide profound muscle relaxation throughout the body. Muscle blocking agents are neither anesthetic nor analgesic; therefore inappropriately used may cause paralysis in fully conscious and feeling pain patient. They cause paralysis of all skeletal muscles, also diaphragm and intercostal muscles when given in higher doses. Intraoperative management includes maintaining stable physiological conditions, which involves adjusting hemodynamic parameters, ensuring proper ventilation, avoiding variations in temperature, maintain normal blood flow to promote proper oxygen exchange. Neuromuscular blocking agent can cause many side effects like residual paralysis, anaphylactic or anaphylactoid reactions, delayed recovery from anesthesia, histamine release, recurarization. Therefore reverse drug like neostigmine (with glikopyrolat) or edrofonium (with atropine) should be used in case of a life-threatening situation. Another useful drug is sugammadex, although the cost of this drug strongly limits its use. Muscle relaxant improves surgical conditions during spinal surgery, especially in heavily muscled individuals. They are also used to facilitate the replacement of dislocated joints as they improve conditions during fracture reduction. It is important to emphasize that in a patient with muscle weakness neuromuscular blocking agents may result in intraoperative and early postoperative cardiovascular and respiratory complications, as well as prolonged recovery from anesthesia. This should not appear in patients with recent spine fracture or luxation. Therefore it is believed that neuromuscular blockers could be useful during spine stabilization procedures.

Keywords: anesthesia, dog, neuromuscular block, spine surgery

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Authors: Banu Pradheepa Kamarajan, Muthusamy Ananthasubramanian

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Biofilm forming Pseudomonads occupy the top third position in causing hospital acquired infections. P. aeruginosa is notoriously known for its tendency to develop drug resistance. Major classes of drug such as β-lactams, aminoglycosides, quinolones, and polymyxins are found ineffective against multi-drug resistance Pseudomonas. To combat the infections, rather than administration of a single antibiotic, use of combinations (tobramycin and essential oils from plants and/or silver nanoparticles, chitosan, nitric oxide, cis-2-decenoic acid) in single formulation are suggested to control P. aeruginosa biofilms. Conventional techniques to prevent hospital-acquired implant infections such as coatings with antibiotics, controlled release of antibiotics from the implant material, contact-killing surfaces, coating the implants with functional DNase I and, coating with glycoside hydrolase are being followed. Coatings with bioactive components besides having limited shelf-life, require cold-chain and, are likely to fail when bacteria develop resistance. Recently identified nano-scale physical architectures on the insect wings are expected to have potential bactericidal property. Nanopillars are bactericidal to Staphylococcus aureus, Bacillus subtilis, K. pnuemoniae and few species of Pseudomonas. Our study aims to investigate the survival rate of biofilm forming Pseudomonas aeruginosa strain over non-biofilm forming strain on the nanopillar architecture of dragonfly (Pantala flavescens) wing. Dragonflies were collected near house-hold areas and, insect identification was carried out by the Department of Entomology, Tamilnadu Agricultural University, Coimbatore, India. Two strains of P. aeruginosa such as PAO1 (potent biofilm former) and MTCC 1688 (non-weak biofilm former) were tested against the glass coverslip (control) and wings of dragonfly (test) for 48 h. The wings/glass coverslips were incubated with bacterial suspension in 48-well plate. The plates were incubated at 37 °C under static condition. Bacterial attachment on the nanopillar architecture of the wing surface was visualized using FESEM. The survival rate of P. aeruginosa was tested using colony counting technique and flow cytometry at 0.5 h, 1 h, 2 h, 7 h, 24 h, and 48 h post-incubation. Cell death was analyzed using propidium iodide staining and DNA quantification. The results indicated that the survival rate of non-biofilm forming P. aeruginosa is 0.2 %, whilst that of biofilm former is 45 % on the dragonfly wings at the end of 48 h. The reduction in the survival rate of biofilm and non-biofilm forming P. aeruginosa was 20% and 40% respectively on the wings compared to the glass coverslip. In addition, Fourier Transformed Infrared Radiation was used to study the modification in the surface chemical composition of the wing during bacterial attachment and, post-sonication. This result indicated that the chemical moieties are not involved in the bactericidal property of nanopillars by the conserved characteristic peaks of chitin pre and post-sonication. The nanopillar architecture of the dragonfly wing efficiently deters the survival of non-biofilm forming P. aeruginosa, but not the biofilm forming strain. The study highlights the ability of biofilm formers to survive on wing architecture. Understanding this survival strategy will help in designing the architecture that combats the colonization of biofilm forming pathogens.

Keywords: biofilm, nanopillars, Pseudomonas aeruginosa, survival rate

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Authors: Kostas Kouvaris, Anastasia Eleftheriou, Georgios A. Sarantitis, Apostolos Chondronasios

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To achieve the objective of almost zero carbon energy solutions by 2050, the EU needs to accelerate the development of integrated, highly efficient and environmentally friendly solutions. In this direction, district heating and cooling (DHC) emerges as a viable and more efficient alternative to conventional, decentralized heating and cooling systems, enabling a combination of more efficient renewable and competitive energy supplies. In this paper, we develop a forecasting tool for near real-time local weather and thermal energy demand predictions for an entire DHC network. In this fashion, we are able to extend the functionality and to improve the energy efficiency of the DHC network by predicting and adjusting the heat load that is distributed from the heat generation plant to the connected buildings by the heat pipe network. Two case-studies are considered; one for Vransko, Slovenia and one for Montpellier, France. The data consists of i) local weather data, such as humidity, temperature, and precipitation, ii) weather forecast data, such as the outdoor temperature and iii) DHC operational parameters, such as the mass flow rate, supply and return temperature. The external temperature is found to be the most important energy-related variable for space conditioning, and thus it is used as an external parameter for the energy demand models. For the development of the forecasting tool, we use state-of-the-art deep neural networks and more specifically, recurrent networks with long-short-term memory cells, which are able to capture complex non-linear relations among temporal variables. Firstly, we develop models to forecast outdoor temperatures for the next 24 hours using local weather data for each case-study. Subsequently, we develop models to forecast thermal demand for the same period, taking under consideration past energy demand values as well as the predicted temperature values from the weather forecasting models. The contributions to the scientific and industrial community are three-fold, and the empirical results are highly encouraging. First, we are able to predict future thermal demand levels for the two locations under consideration with minimal errors. Second, we examine the impact of the outdoor temperature on the predictive ability of the models and how the accuracy of the energy demand forecasts decreases with the forecast horizon. Third, we extend the relevant literature with a new dataset of thermal demand and examine the performance and applicability of machine learning techniques to solve real-world problems. Overall, the solution proposed in this paper is in accordance with EU targets, providing an automated smart energy management system, decreasing human errors and reducing excessive energy production.

Keywords: machine learning, LSTMs, district heating and cooling system, thermal demand

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Authors: Kamel Belammi, Houria Fatrim

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imbalanced data set, a problem often found in real world application, can cause seriously negative effect on classification performance of machine learning algorithms. There have been many attempts at dealing with classification of imbalanced data sets. In medical diagnosis classification, we often face the imbalanced number of data samples between the classes in which there are not enough samples in rare classes. In this paper, we proposed a learning method based on a cost sensitive extension of Least Mean Square (LMS) algorithm that penalizes errors of different samples with different weight and some rules of thumb to determine those weights. After the balancing phase, we applythe different classifiers (support vector machine (SVM), k- nearest neighbor (KNN) and multilayer neuronal networks (MNN)) for balanced data set. We have also compared the obtained results before and after balancing method.

Keywords: multilayer neural networks, k- nearest neighbor, support vector machine, imbalanced medical data, least mean square algorithm, diabetes

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Authors: Mami Miyasaka, Kaichi Yanaoka

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Attention Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder characterized by inattention, hyperactivity, and impulsivity; symptoms often manifest during childhood. In children with ADHD, the development of inhibitory processes is impaired. Inhibitory control allows people to avoid processing unnecessary stimuli and to behave appropriately in various situations; thus, people with ADHD require interventions to improve inhibitory control. Positive or negative reinforcements (i.e., reward or punishment) help improve the performance of children with such difficulties. However, in order to optimize impact, reward and punishment must be presented immediately following the relevant behavior. In regular elementary school classrooms, such supports are uncommon; hence, an alternative practical intervention method is required. One potential intervention involves setting goals to keep children motivated to perform tasks. This study examined whether goal setting improved inhibitory performances, especially for children with severe ADHD-related symptoms. We also focused on giving feedback on children's task performances. We expected that giving children feedback would help them set reasonable goals and monitor their performance. Feedback can be especially effective for children with severe ADHD-related symptoms because they have difficulty monitoring their own performance, perceiving their errors, and correcting their behavior. Our prediction was that goal setting by itself would be effective for children with mild ADHD-related symptoms, and goal setting based on feedback would be effective for children with severe ADHD-related symptoms. Japanese elementary school children and their parents were the sample for this study. Children performed two kinds of go/no-go tasks, and parents completed a checklist about their children's ADHD symptoms, the ADHD Rating Scale-IV, and the Conners 3rd edition. The go/no-go task is a cognitive task to measure inhibitory performance. Children were asked to press a key on the keyboard when a particular symbol appeared on the screen (go stimulus) and to refrain from doing so when another symbol was displayed (no-go stimulus). Errors obtained in response to a no-go stimulus indicated inhibitory impairment. To examine the effect of goal-setting on inhibitory control, 37 children (Mage = 9.49 ± 0.51) were required to set a performance goal, and 34 children (Mage = 9.44 ± 0.50) were not. Further, to manipulate the presence of feedback, in one go/no-go task, no information about children’s scores was provided; however, scores were revealed for the other type of go/no-go tasks. The results revealed a significant interaction between goal setting and feedback. However, three-way interaction between ADHD-related inattention, feedback, and goal setting was not significant. These results indicated that goal setting was effective for improving the performance of the go/no-go task only with feedback, regardless of ADHD severity. Furthermore, we found an interaction between ADHD-related inattention and feedback, indicating that informing inattentive children of their scores made them unexpectedly more impulsive. Taken together, giving feedback was, unexpectedly, too demanding for children with severe ADHD-related symptoms, but the combination of goal setting with feedback was effective for improving their inhibitory control. We discuss effective interventions for children with ADHD from the perspective of goal setting and feedback. This work was supported by the 14th Hakuho Research Grant for Child Education of the Hakuho Foundation.

Keywords: attention deficit disorder with hyperactivity, feedback, goal-setting, go/no-go task, inhibitory control

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Authors: M. F. Haroun, T. A. Gulliver

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In this paper, an encryption algorithm is proposed for real-time image encryption. The scheme employs a dual chaotic generator based on a three dimensional (3D) discrete Lorenz attractor. Encryption is achieved using non-autonomous modulation where the data is injected into the dynamics of the master chaotic generator. The second generator is used to permute the dynamics of the master generator using the same approach. Since the data stream can be regarded as a random source, the resulting permutations of the generator dynamics greatly increase the security of the transmitted signal. In addition, a technique is proposed to mitigate the error propagation due to the finite precision arithmetic of digital hardware. In particular, truncation and rounding errors are eliminated by employing an integer representation of the data which can easily be implemented. The simple hardware architecture of the algorithm makes it suitable for secure real-time applications.

Keywords: chaotic systems, image encryption, non-autonomous modulation, FPGA

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Authors: Weijing Zhou, Yuting Lei, Francis Nolan

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In the domain of second language acquisition, whenever pronunciation errors or acquisition difficulties are found, researchers habitually attribute them to the negative transfer of the native language or local dialect. To what extent do Mandarin and local dialects affect English phonological acquisition for Chinese learners of English as a foreign language (EFL)? Little evidence, however, has been found via empirical research in China. To address this core issue, the present study conducted phonetic experiments to explore the roles of local dialects and Mandarin in Chinese EFL learners’ acquisition of L2 English consonants. Besides Mandarin, the sole national language in China, Suzhou dialect was selected as the target local dialect because of its distinct phonology from Mandarin. The experimental group consisted of 30 junior English majors at Yangzhou University, who were born and lived in Suzhou, acquired Suzhou Dialect since their early childhood, and were able to communicate freely and fluently with each other in Suzhou Dialect, Mandarin as well as English. The consonantal target segments were all the consonants of English, Mandarin and Suzhou Dialect in typical carrier words embedded in the carrier sentence Say again. The control group consisted of two Suzhou Dialect experts, two Mandarin radio broadcasters, and two British RP phoneticians, who served as the standard speakers of the three languages. The reading corpus was recorded and sampled in the phonetic laboratories at Yangzhou University, Soochow University and Cambridge University, respectively, then transcribed, segmented and analyzed acoustically via Praat software, and finally analyzed statistically via EXCEL and SPSS software. The main findings are as follows: First, in terms of correct acquisition rates (CARs) of all the consonants, Mandarin ranked top (92.83%), English second (74.81%) and Suzhou Dialect last (70.35%), and significant differences were found only between the CARs of Mandarin and English and between the CARs of Mandarin and Suzhou Dialect, demonstrating Mandarin was overwhelmingly more robust than English or Suzhou Dialect in subjects’ multilingual phonological ecology. Second, in terms of typical acoustic features, the average duration of all the consonants plus the voice onset time (VOT) of plosives, fricatives, and affricatives in 3 languages were much longer than those of standard speakers; the intensities of English fricatives and affricatives were higher than RP speakers but lower than Mandarin and Suzhou Dialect standard speakers; the formants of English nasals and approximants were significantly different from those of Mandarin and Suzhou Dialects, illustrating the inconsistent acoustic variations between the 3 languages. Thirdly, in terms of typical pronunciation variations or errors, there were significant interlingual interactions between the 3 consonant systems, in which Mandarin consonants were absolutely dominant, accounting for the strong transfer from L1 Mandarin to L2 English instead of from earlier-acquired L1 local dialect to L2 English. This is largely because the subjects were knowingly exposed to Mandarin since their nursery and were strictly required to speak in Mandarin through all the formal education periods from primary school to university.

Keywords: acquisition of L2 English consonants, role of Mandarin, role of local dialect, Chinese EFL learners from Suzhou Dialect areas

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Authors: Tejinder Singh

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Information system is the flow of data from different levels to different directions for decision making and data operations in information system (IS). Data can be violated by different manner like manual or technical errors, data tampering or loss of integrity. Security system called firewall of IS is effected by such type of violations. The flow of data among various levels of Information System is done by networking system. The flow of data on network is in form of packets or frames. To protect these packets from unauthorized access, virus attacks, and to maintain the integrity level, network security is an important factor. To protect the data to get pirated, various security techniques are used. This paper represents the various security techniques and signifies different harmful attacks with the help of detailed data analysis. This paper will be beneficial for the organizations to make the system more secure, effective, and beneficial for future decisions making.

Keywords: information systems, data integrity, TCP/IP network, vulnerability, decision, data

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Authors: Masoud Mirzaee, Ghobad Behzadi Pour

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An aircraft tire is designed to tolerate extremely heavy loads for a short duration. The number of tires increases with the weight of the aircraft, as it is needed to be distributed more evenly. Generally, aircraft tires work at high pressure, up to 200 psi (14 bar; 1,400 kPa) for airliners and higher for business jets. Tire assemblies for most aircraft categories provide a recommendation of compressed nitrogen that supports the aircraft’s weight on the ground, including a mechanism for controlling the aircraft during taxi, takeoff; landing; and traction for braking. Accurate tire pressure is a key factor that enables tire assemblies to perform reliably under high static and dynamic loads. Concerning ambient temperature change, considering the condition in which the temperature between the origin and destination airport was different, tire pressure should be adjusted and inflated to the specified operating pressure at the colder airport. This adjustment superseding the normal tire over an inflation limit of 5 percent at constant ambient temperature is required because the inflation pressure remains constant to support the load of a specified aircraft configuration. On the other hand, without this adjustment, a tire assembly would be significantly under/over-inflated at the destination. Due to an increase of human errors in the aviation industry, exorbitant costs are imposed on the airlines for providing consumable parts such as aircraft tires. The existence of an intelligent system to adjust the aircraft tire pressure based on weight, load, temperature, and weather conditions of origin and destination airports, could have a significant effect on reducing the aircraft maintenance costs, aircraft fuel and further improving the environmental issues related to the air pollution. An intelligent tire pressure regulation system (ITPRS) contains a processing computer, a nitrogen bottle with 1800 psi, and distribution lines. Nitrogen bottle’s inlet and outlet valves are installed in the main wheel landing gear’s area and are connected through nitrogen lines to main wheels and nose wheels assy. Controlling and monitoring of nitrogen will be performed by a computer, which is adjusted according to the calculations of received parameters, including the temperature of origin and destination airport, the weight of cargo loads and passengers, fuel quantity, and wind direction. Correct tire inflation and deflation are essential in assuring that tires can withstand the centrifugal forces and heat of normal operations, with an adequate margin of safety for unusual operating conditions such as rejected takeoff and hard landings. ITPRS will increase the performance of the aircraft in all phases of takeoff, landing, and taxi. Moreover, this system will reduce human errors, consumption materials, and stresses imposed on the aircraft body.

Keywords: avionic system, improve efficiency, ITPRS, human error, reduced cost, tire pressure

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Authors: Teguh Sugiarto

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Background: The research aims to explore if there is fraud in a financial statement, use the Act stated that Benford's distribution all digits must compare the number will follow the trend of lower number. Research methods: This research uses all the analysis number being in Benford's law. After receiving the results of the analysis of all the digits, the author makes a distinction between implementation using the scale above and below 5%, the rate of occurrence of difference. With the number which have differences in the range of 5%, then can do the follow-up and the detection of the onset of fraud against the financial statements. The findings: From the research that has been done can be drawn the conclusion that the average of all numbers appear in the financial statements, and compare the rates of occurrence of numbers according to the characteristics of Benford's law. About the existence of errors and fraud in the financial statements of PT medco Energy Tbk did not occur. Conclusions: The study concludes that Benford's law can serve as indicator tool in detecting the possibility of in financial statements to case studies of PT Medco Energy Tbk for the fiscal year 2000-2010.

Keywords: Benford law, first digits, all digits number Benford law, financial statement

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Authors: Reem AlKabbi, Hayat Ali, Mariam Yasser

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Nowadays, eGovernment websites are becoming indispensable for public, business, personal efficiency or even improvement of livelihoods. Using these websites, citizens undertake number of tasks that would otherwise be difficult or impossible. However, many of these websites are not accessible to all people' types including People with Disabilities (PWDs). Through Web Accessibility Guidelines, Web developers can develop Web applications that are accessible to PWDs. This research is to investigate the Accessibility of eGovernment websites in Kingdom of Bahrain. The accessibility was measured using Web Content Accessibility Guidelines (WCAG) and section 508. For the evaluation purpose, some automatic tools were used. Samples of 43 eGovernment websites were selected. The accessibility of the websites was analyzed by using several automatic evaluation tools such as Total Validator and Functional Accessibility Evaluator (FAE). The evaluation process revealed several errors according to the accessibility guidelines. This research provides few recommendations for further improvement of accessibility features of eGovernment websites based on the highlighted issues and key findings reported in this research.

Keywords: website accessibility, W3C, PWD, e-government

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Authors: Mike Yaw Osei-Atweneboana, John Asiedu Larbi, Edward Jenner Tettevi

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Background: The lymphatic filariasis (LF) control programme has been on-going in Ghana since 2000. This community-wide approach involves the use of ivermectin (IVM) and albendazole (ALB). Soil-transmitted helminth (STH) infections control is augmented within this programme; however, in areas where LF is not prevalent, albendazole alone is administered to school children. The purpose of this study was therefore, to determine the efficacy of albendazole against soils transmitted helminths and the impact of mass drug administration of albendazole and ivermectin on the health status of children of school going age and pregnant women. Material/Methods: This was a twelve months longitudinal study. A total of 412 subjects including school children (between the ages of 2-17 years) and pregnant women were randomly selected from four endemic communities in Kpandai district of the Northern region. Coprological assessment for parasites was based on the Kato–Katz technique in both dry and rainy seasons at baseline, 21 days and 3 months post-treatment. Single-dose albendazole treatment was administered to all patients at baseline. Preserved samples are currently under molecular studies to identify possible single nucleotide polymorphism (SNP) within the beta tubulin gene which is associated with benzimidazole resistance. Results: Of all the parasites found (hookworm, Trichuris trichiura, Hymenolepis nana, and Taenia sp.); hookworm was the most prevalent. In the dry season, the overall STHs prevalence at pre-treatment was 29%, while 9% and 13% prevalence was recorded at 21 days, and three months after treatment respectively. However, in the rainy season, the overall STHs prevalence was 8%, while 4% and 12% was recorded at 21 days and three months respectively after ALB treatment. In general, ALB treatment resulted in an overall hookworm egg count reduction rate of 89% in the dry season and 93% in the rainy season, while the T. trichiura egg count reduction rate was 100% in both seasons. Conclusions: STH infections still remains a significant public health burden in Ghana. Hookworm infection seems to respond poorly or sub-optimally to ALB, raising concerns of possible emergence of resistance which may lead to a major setback for the control and elimination of STH infections, especially hookworm infections.

Keywords: hookworm, sub-optimal response, albendazole, trichuriasis, soil-transmitted helminths

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Authors: Elvin P. Chizenga, Heidi Abrahamse

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Cancer cell resistance to therapy is the main cause of treatment failures and the poor prognosis of cancer convalescence. The progression of cervical cancer to other parts of the genitourinary system and the reported recurrence rates are overwhelming. Current treatments, including surgery, chemo and radiation have been inefficient in eradicating the tumor cells. These treatments are also associated with poor prognosis and reduced quality of life, including fertility loss. This has inspired the need for the development of new treatment modalities to eradicate cervical cancer successfully. Photodynamic Therapy (PDT) is a modern treatment modality that induces cell death by photochemical interactions of light and a photosensitizer, which in the presence of molecular oxygen, yields a set of chemical reactions that generate Reactive Oxygen Species (ROS) and other free radical species causing cell damage. Enhancing PDT using modified drug delivery can increase the concentration of the photosensitizer in the tumor cells, and this has the potential to maximize its therapeutic efficacy. In cervical cancer, all infected cells constitutively express genes of the E6 and E7 HPV viral oncoproteins, resulting in high concentrations of E6 and E7 in the cytoplasm. This provides an opportunity for active targeting of cervical cancer cells using immune-mediated drug delivery to maximize therapeutic efficacy. The use of nanoparticles in PDT has also proven effective in enhancing therapeutic efficacy. Gold nanoparticles (AuNps) in particular, are explored for their use in biomedicine due to their biocompatibility, low toxicity, and enhancement of drug uptake by tumor cells. In this present study, a biomolecule comprising of AuNPs, anti-E6 monoclonal antibodies, and Aluminium Phthalocyanine photosensitizer was synthesized for use in targeted PDT of cervical cancer. The AuNp-Anti-E6-Sulfonated Aluminium Phthalocyanine mix (AlPcSmix) photosensitizing biomolecule was synthesized by coupling AuNps and anti-E6 monoclonal antibodies to the AlPcSmix via Polyethylene Glycol (PEG) chemical links. The final product was characterized using Transmission Electron Microscope (TEM), Zeta Potential, Uv-Vis Spectrophotometry, Fourier Transform Infrared Spectroscopy (FTIR), and X-ray diffraction (XRD), to confirm its chemical structure and functionality. To observe its therapeutic role in treating cervical cancer, cervical cancer cells, HeLa cells were seeded in 3.4 cm² diameter culture dishes at a concentration of 5x10⁵ cells/ml, in vitro. The cells were treated with varying concentrations of the photosensitizing biomolecule and irradiated using a 673.2 nm wavelength of laser light. Post irradiation cellular responses were performed to observe changes in morphology, viability, proliferation, cytotoxicity, and cell death pathways induced. Dose-Dependent response of the cells to treatment was demonstrated as significant morphologic changes, increased cytotoxicity, and decreased cell viability and proliferation This study presented a synthetic biomolecule for targeted PDT of cervical cancer. The study suggested that PDT using this AuNp- Anti-E6- AlPcSmix photosensitizing biomolecule is a very effective treatment method for the eradication of cervical cancer cells, in vitro. Further studies in vivo need to be conducted to support the use of this biomolecule in treating cervical cancer in clinical settings.

Keywords: anti-E6 monoclonal antibody, cervical cancer, gold nanoparticles, photodynamic therapy

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Authors: Rauf R. Hussein, Devon M. Ramey

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Integrating Ground Penetrating Radar (GPR) with Geographic Information Systems (GIS) can provide valuable insights for various applications, such as archaeology, transportation, and utility locating. Although there has been progress toward automating the integration of GPR data with GIS, fully automatic integration has not been achieved yet. Additionally, manually integrating GPR data with GIS can be a time-consuming and error-prone process. In this study, actual, real-world GPR applications are presented, and a software named GPR-GIS 10 is created to interactively extract subsurface targets from GPR radargrams and automatically integrate them into GIS. With this software, it is possible to quickly and reliably integrate the two techniques to create informative subsurface maps. The results indicated that automatic integration of GPR with GIS can be an efficient tool to map and view any subsurface targets in their appropriate location in a 3D space with the needed precision. The findings of this study could help GPR-GIS integrators save time and reduce errors in many GPR-GIS applications.

Keywords: GPR, GIS, GPR-GIS 10, drone technology, automation

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Authors: Christopher Holroyd

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With the various terrorist organizations and drug cartels that are currently active, there is a myriad of security concerns facing countries around the world. Organizations that focus their attacks on others through terror, such as what is seen with the Islamic State of Iraq and the Levant (ISIS), have no boundaries when it comes to doing what is needed to fulfill their desired intent. For countries such as Iraq, who have been trying to rebuild their country since the fall of the Saddam Hussein Regime, organizations such as Al-Qaeda and ISIS have been impeding the country’s efforts toward peace and stability. One method utilized by terrorist organizations around the world is human trafficking. This method is one that is seen around the world; modern slavery is still exploited by those who have no concern for human decency and morality, their only concern is to achieve their goals by any means. It is understandable that some people may not have even heard of 'modern slavery', or they just might not believe that it is even an issue in today’s world. Organizations such as ISIS are not the only ones in the world that seek to benefit from the immoral trading of humans. Various drug cartels in the world, such as those seen in Mexico and Central America, have recently begun to take part in the trade – moving humans from state to state, or country to country, to better fuel their overall operations. This now makes the possibility of human trafficking more real for those in the United States because of the proximity of the cartels to the southern border of the country. An issue that, at one time, might have only seen as a distant threat, is now close to home for those in the United States. Looking at these two examples is how we begin to understand why human trafficking is utilized by various organizations around the world. This trade of human beings and the violation of basic human rights is a plague that effects the entire world and not just those that are in a country other than your own. One of the security issues that stem from the trade includes the movement and recruitment of members of the organizations. With individuals being smuggled from one location to another in secrecy, this only puts those trying to combat this trade at a disadvantage. This creates concern over the accurate number of potential recruits, combatants, and other individuals who are working against the host nation, and for the mission of the cartel or terrorist organization they are a part of. An uphill battle is created, and the goals of peace and stability are now harder to reach. Aside from security aspects, it cannot be forgotten that those being traded and forced into slavery, are being done so against their will. Families are separated, children trained to be fighters or worse. This makes the goal of eradicating human trafficking even more dire and important.

Keywords: human trafficking, reconstruction, security, terrorism

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Authors: Olga A. Gnatyuk

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The article is devoted to the phenomenon of interference that occurs in the case of the Russian-Spanish language contact. The questions of the definition of the term and levels, as well as prerequisites of interference occurrence, are considered. Interference, which is an essential part of bilingualism, may become apparent at different linguistic levels. Interference is especially evident in oral speech. The article reviews some examples of grammatical interference in Russian-Spanish bilingualism of Russian immigrants living in Spain. According to the results of the research, some cases of mother-tongue interference in Russian-Speaking Spanish language learners’ speech were revealed. Special attention is paid to such key spheres of grammatical interference as articles, personal pronouns, gender, and number of nouns. In the research, the drop of a link-verb, as well as its usage in some incorrect form, are observed in Russian immigrants’ speech. Conclusions are drawn that in the Spanish language, interference errors appear because of a consequence of both the absence in the Russian language of certain phenomena and categories of the Spanish language and the discrepancy of the linguistic systems of the two languages.

Keywords: bilingualism, interference, grammatical interference, Russian language, Spanish language

Procedia PDF Downloads 138

Authors: Edlira Donefski, Tina Donefski, Lorenc Ekonomi

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Edgeworth Approximation, Bootstrap, and Monte Carlo Simulations have considerable impacts on achieving certain results related to different problems taken into study. In our paper, we have treated a financial case related to the effect that has the components of a cash-flow of one of the most successful businesses in the world, as the financial activity, operational activity, and investment activity to the cash and cash equivalents at the end of the three-months period. To have a better view of this case, we have created a vector autoregression model, and after that, we have generated the impulse responses in the terms of asymptotic analysis (Edgeworth Approximation), Monte Carlo Simulations, and residual bootstrap based on the standard errors of every series created. The generated results consisted of the common tendencies for the three methods applied that consequently verified the advantage of the three methods in the optimization of the model that contains many variants.

Keywords: autoregression, bootstrap, edgeworth expansion, Monte Carlo method

Procedia PDF Downloads 129

Authors: Igbakura I. Luga, Alex A. Adikwu

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A comparison of resistance to quinolones was carried out on isolates of Shiga toxin-producing Escherichia coliO157:H7 from cattle and mecA and nuc genes harbouring Staphylococcus aureus from pigs. The isolates were separately tested in the first and current decades of the 21^st century. The objective was to demonstrate the dissemination of resistance to this frontline class of antibiotic by bacteria from food animals and bring to the limelight the spread of antibiotic resistance in Nigeria. A total of 10 isolates of the E. coli O157:H7 and 9 of mecA and nuc genes harbouring S. aureus were obtained following isolation, biochemical testing, and serological identification using the Remel Wellcolex E. coli O157:H7 test. Shiga toxin-production screening in the E. coli O157:H7 using the verotoxin E. coli reverse passive latex agglutination (VTEC-RPLA) test; and molecular identification of the mecA and nuc genes in S. aureus. Detection of the mecA and nuc genes were carried out using the protocol by the Danish Technical University (DTU) using the following primers mecA-1:5'-GGGATCATAGCGTCATTATTC-3', mecA-2: 5'-AACGATTGTGACACGATAGCC-3', nuc-1: 5'-TCAGCAAATGCATCACAAACAG-3', nuc-2: 5'-CGTAAATGCACTTGCTTCAGG-3' for the mecA and nuc genes, respectively. The nuc genes confirm the S. aureus isolates and the mecA genes as being methicillin-resistant and so pathogenic to man. The fluoroquinolones used in the antibiotic resistance testing were norfloxacin (10 µg) and ciprofloxacin (5 µg) in the E. coli O157:H7 isolates and ciprofloxacin (5 µg) in the S. aureus isolates. Susceptibility was tested using the disk diffusion method on Muller-Hinton agar. Fluoroquinolone resistance was not detected from isolates of E. coli O157:H7 from cattle. However, 44% (4/9) of the S. aureus were resistant to ciprofloxacin. Resistance of up to 44% in isolates of mecA and nuc genes harbouring S. aureus is a compelling evidence for the rapid spread of antibiotic resistance from bacteria in food animals from Nigeria. Ciprofloxacin is the drug of choice for the treatment of Typhoid fever, therefore widespread resistance to it in pathogenic bacteria is of great public health significance. The study concludes that antibiotic resistance in bacteria from food animals is on the increase in Nigeria. The National Food and Drug Administration and Control (NAFDAC) agency in Nigeria should implement the World Health Organization (WHO) global action plan on antimicrobial resistance. A good starting point can be coordinating the WHO, Office of International Epizootics (OIE), Food and Agricultural Organization (FAO) tripartite draft antimicrobial resistance monitoring and evaluation (M&E) framework in Nigeria.

Keywords: Fluoroquinolone, Nigeria, resistance, Staphylococcus aureus

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Authors: Mohamed A. Etman, Mona G. Abd-Elnasser, Mohamed A. Shams-Eldin, Aly H. Nada

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Orally disintegrating tablets (ODTs) are gaining importance as new drug delivery systems and emerged as one of the popular and widely accepted dosage forms, especially for the pediatric and geriatric patients. Their advantages such as administration without water, anywhere, anytime lead to their suitability to geriatric and pediatric patients. They are also suitable for the mentally ill, the bed-ridden and patients who do not have easy access to water. The benefits, in terms of patient compliance, rapid onset of action, increased bioavailability, and good stability make these tablets popular as a dosage form of choice in the current market. These dosage forms dissolve or disintegrate in the oral cavity within a matter of seconds without the need of water or chewing. Desloratadine is a tricyclic antihistaminic, which has a selective and peripheral H1-antagonist action. It is an antagonist at histamine H1 receptors, and an antagonist at all subtypes of the muscarinic acetylcholine receptor. Desloratadine is the major metabolite of loratadine. Twelve different placebos ODT were prepared (F1-F12) using different functional excipients. They were evaluated for their compressibility, hardness and disintegration time. All formulations were non sticky except four formulations; namely (F8, F9, F10, F11). All formulations were compressible with the exception of (F2). Variable disintegration times were found ranging between 20 and 120 seconds. It was found that (F12) showed the least disintegration time (20 secs) without showing any sticking which could be due to the use of high percentage of superdisintegrants. Desloratadine showed bitter taste when formulated as ODT without any treatment. Therefore, different techniques were tried in order to mask its bitter taste. Using Eudragit EPO resulted in complete masking of the bitter taste of the drug and increased the acceptability to volunteers. The compressible non sticky formulations (F1, F3, F4, F5, F6, F7 and F12) were subjected to further evaluation tests after addition of coated desloratadine, including weight uniformity, wetting time, and friability testing.. Fairly good weight uniformity values were observed in all the tested formulations. F12 exhibiting the shortest wetting time (14.7 seconds) and consequently the lowest (20 seconds) disintegration time. Dissolution profile showed that 100% desloratadine release was attained after only 2.5 minutes from the prepared ODT (F12) with dissolution efficiency of 95%.

Keywords: Desloratadine, orally disintegrating tablets (ODTs), formulations, taste masking

Procedia PDF Downloads 435

Authors: Amr Saeb, Khalid Al-Rubeaan, Mohamed Abouelhoda, Manojkumar Selvaraju, Hamsa Tayeb

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Background: P. mirabilis is a common uropathogenic bacterium that can cause major complications in patients with long-standing indwelling catheters or patients with urinary tract anomalies. In addition, P. mirabilis is a common cause of chronic osteomyelitis in diabetic foot ulcer (DFU) patients. Methodology: P. mirabilis SCDR1 was isolated from a diabetic ulcer patient. We examined P. mirabilis SCDR1 levels of resistance against nano-silver colloids, the commercial nano-silver and silver containing bandages and commonly used antibiotics. We utilized next generation sequencing techniques (NGS), bioinformatics, phylogenetic analysis and pathogenomics in the identification and characterization of the infectious pathogen. Results: P. mirabilis SCDR1 is a multi-drug resistant isolate that also showed high levels of resistance against nano-silver colloids, nano-silver chitosan composite and the commercially available nano-silver and silver bandages. The P. mirabilis-SCDR1 genome size is 3,815,621 bp with G+C content of 38.44%. P. mirabilis-SCDR1 genome contains a total of 3,533 genes, 3,414 coding DNA sequence genes, 11, 10, 18 rRNAs (5S, 16S, and 23S), and 76 tRNAs. Our isolate contains all the required pathogenicity and virulence factors to establish a successful infection. P. mirabilis SCDR1 isolate is a potential virulent pathogen that despite its original isolation site, wound, it can establish kidney infection and its associated complications. P. mirabilis SCDR1 contains several mechanisms for antibiotics and metals resistance including, biofilm formation, swarming mobility, efflux systems, and enzymatic detoxification. Conclusion: P. mirabilis SCDR1 is the spontaneous nano-silver resistant bacterial strain. P. mirabilis SCDR1 strain contains all reported pathogenic and virulence factors characteristic for the species. In addition, it possesses several mechanisms that may lead to the observed nano-silver resistance.

Keywords: Proteus mirabilis, multi-drug resistance, silver nanoparticles, resistance, next generation sequencing techniques, genome analysis, bioinformatics, phylogeny, pathogenomics, diabetic foot ulcer, xenobiotics, multidrug resistance efflux, biofilm formation, swarming mobility, resistome, glutathione S-transferase, copper/silver efflux system, altruism

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Authors: Cynthia K. Burzell

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Aequor's Founder, a Marine and Medical Microbiologist, discovered novel, non-toxic chemicals in the ocean that uniquely remove biofilm in minutes and prevent its formation for days. These chemicals and over 70 synthesized analogs that Aequor developed can replace thousands of toxic biocides used in consumer and industrial products and, as new drug candidates, kill biofilm-forming bacteria and fungi Superbugs -the antimicrobial-resistant (AMR) pathogens for which there is no cure. Cynthia Burzell, PhD., is a Marine and Medical Microbiologist studying natural mechanisms that inhibit biofilm formation on surfaces in contact with water. In 2002, she discovered a new genus and several new species of marine microbes that produce small molecules that remove biofilm in minutes and prevent its formation for days. The molecules include new antimicrobials that can replace thousands of toxic biocides used in consumer and industrial products and can be developed into new drug candidates to kill the biofilm-forming bacteria and fungi -- including the antimicrobial-resistant (AMR) Superbugs for which there is no cure. Today, Aequor has over 70 chemicals that are divided into categories: (1) Novel natural chemicals. Lonza validated that the primary natural chemical removed biofilm in minutes and stated: "Nothing else known can do this at non-toxic doses." (2) Specialty chemicals. 25 of these structural analogs are already approved under the U.S. Environmental Protection Agency (EPA)'s Toxic Substances Control Act, certified as "green" and available for immediate sale. These have been validated for the following agro-industrial verticals: (a) Surface cleaners: The U.S. Department of Agriculture validated that low concentrations of Aequor's formulations provide deep cleaning of inert, nano and organic surfaces and materials; (b) Water treatments: NASA validated that one dose of Aequor's treatment in the International Space Station's water reuse/recycling system lasted 15 months without replenishment. DOE validated that our treatments lower energy consumption by over 10% in buildings and industrial processes. Future validations include pilot projects with the EPA to test efficacy in hospital plumbing systems. (c) Algae cultivation and yeast fermentation: The U.S. Department of Energy (DOE) validated that Aequor's treatment boosted biomass of renewable feedstocks by 40% in half the time -- increasing the profitability of biofuels and biobased co-products. DOE also validated increased yields and crop protection of algae under cultivation in open ponds. A private oil and gas company validated decontamination of oilfield water. (3) New structural analogs. These kill Gram-negative and Gram-positive bacteria and fungi alone, in combinations with each other, and in combination with low doses of existing, ineffective antibiotics (including Penicillin), "potentiating" them to kill AMR pathogens at doses too low to trigger resistance. Both the U.S. National Institutes for Health (NIH) and Department of Defense (DOD) has executed contracts with Aequor to provide the pre-clinical trials needed for these new drug candidates to enter the regulatory approval pipelines. Aequor seeks partners/licensees to commercialize its specialty chemicals and support to evaluate the optimal methods to scale-up of several new structural analogs via activity-guided fractionation and/or biosynthesis in order to initiate the NIH and DOD pre-clinical trials.

Keywords: biofilm, potentiation, prevention, removal

Procedia PDF Downloads 77

Authors: Abdulaziz Alakeel, Abdulrahman Alomair, Mohammed Fouda

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Introduction: Methotrexate (MTX) is an antimetabolite used to treat multiple conditions, including neoplastic diseases, severe psoriasis, and rheumatoid arthritis. Skin cancer is the out-of-control growth of abnormal cells in the epidermis, the outermost skin layer, caused by unrepaired DNA damage that triggers mutations. These mutations lead the skin cells to multiply rapidly and form malignant tumors. The aim of this review is to evaluate the risk of skin cancer associated with the use of methotrexate and to suggest regulatory recommendations if required. Methodology: Signal Detection team at Saudi Food and Drug Authority (SFDA) performed a safety review using National Pharmacovigilance Center (NPC) database as well as the World Health Organization (WHO) VigiBase, alongside with literature screening to retrieve related information for assessing the causality between skin cancer and methotrexate. The search conducted in July 2020. Results: Four published articles support the association seen while searching in literature, a recent randomized control trial published in 2020 revealed a statistically significant increase in skin cancer among MTX users. Another study mentioned methotrexate increases the risk of non-melanoma skin cancer when used in combination with immunosuppressant and biologic agents. In addition, the incidence of melanoma for methotrexate users was 3-fold more than the general population in a cohort study of rheumatoid arthritis patients. The last article estimated the risk of cutaneous malignant melanoma (CMM) in a cohort study shows a statistically significant risk increase for CMM was observed in MTX exposed patients. The WHO database (VigiBase) searched for individual case safety reports (ICSRs) reported for “Skin Cancer” and 'Methotrexate' use, which yielded 121 ICSRs. The initial review revealed that 106 cases are insufficiently documented for proper medical assessment. However, the remaining fifteen cases have extensively evaluated by applying the WHO criteria of causality assessment. As a result, 30 percent of the cases showed that MTX could possibly cause skin cancer; five cases provide unlikely association and five un-assessable cases due to lack of information. The Saudi NPC database searched to retrieve any reported cases for the combined terms methotrexate/skin cancer; however, no local cases reported up to date. The data mining of the observed and the expected reporting rate for drug/adverse drug reaction pair is estimated using information component (IC), a tool developed by the WHO Uppsala Monitoring Centre to measure the reporting ratio. Positive IC reflects higher statistical association, while negative values translated as a less statistical association, considering the null value equal to zero. Results showed that a combination of 'Methotrexate' and 'Skin cancer' observed more than expected when compared to other medications in the WHO database (IC value is 1.2). Conclusion: The weighted cumulative pieces of evidence identified from global cases, data mining, and published literature are sufficient to support a causal association between the risk of skin cancer and methotrexate. Therefore, health care professionals should be aware of this possible risk and may consider monitoring any signs or symptoms of skin cancer in patients treated with methotrexate.

Keywords: methotrexate, skin cancer, signal detection, pharmacovigilance

Procedia PDF Downloads 99