Search results for: adverse drug events

Authors: Soo Hyung Kim

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Two different learning approaches were suggested: focusing on factual knowledge or focusing on the embedded meaning in the statements. Each way of learning has positive effects on different question categories, where factual knowledge helps more with simple fact questions, and searching for meaning in given information helps learn causal relationship and the embedded meaning. To test this belief, two groups of learners (12 male and 39 female adults aged 18-37) watched a ten-minute long Youtube video about various factual events of American history, their meaning, and the causal relations of the events. The fact group was asked to focus on factual knowledge in the video, and the meaning group was asked to focus on the embedded meaning in the video. After watching the video, both groups took multiple-choice questions, which consisted of 10 questions asking the factual knowledge addressed in the video and 10 questions asking embedded meaning in the video, such as the causal relationship between historical events and the significance of the event. From ANCOVA analysis, it was found that the factual knowledge showed higher performance on the factual questions than the meaning group, although there was no group difference on the questions about the meaning between the two groups. The finding suggests that teacher instruction plays an important role in learners constructing a different type of knowledge in online learning.

Keywords: factual knowledge, instruction, meaning-based knowledge, online learning

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Authors: Hidayah bt Rahmalan, Marhazli Kipli, Muhammad Suffian Sikandar Ghani, Maisarah Abu, Muhammad Faisal Ashaari, Norlizam Md Sukiban

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This study presents an example of activity management system for e-Masjid implementing elements of usability and sociability. It is expected to resolve the shortcomings of the most e-Masjid that provide lot of activities to their community. However, the data on handling a lot of activities or events in which involve a lot of people will be difficult to manipulate. Thus, this paper presents the usability and sociability element on an activity management system that not only eases the job for the user but being practical for future when the community join any events. For the time being, this activity management system was only applied for Sayyidina Abu Bakar Mosque in Utem, Malacca.

Keywords: e-masjid, usability, sociability, activity management system

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Authors: Bailey Houghtaling, Elena Serrano, Vivica Kraak, Samantha Harden, George Davis, Sarah Misyak

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United States (U.S.) Department of Agriculture Supplemental Nutrition Assistance Program (SNAP) participants are low-income Americans receiving federal dollars for supplemental food and beverage purchases. Participants use a variety of (traditional/non-traditional) SNAP-authorized stores for household dietary purchases - also representing food access points for all Americans. Importantly consumers' food and beverage purchases from non-traditional store formats tend to be higher in saturated fats, added sugars, and sodium when compared to purchases from traditional (e.g., grocery/supermarket) formats. Overconsumption of energy-dense and low-nutrient food and beverage products contribute to high obesity rates and adverse health outcomes that differ in severity among urban/rural U.S. locations and high/low-income populations. Little is known about the SNAP-authorized food store format landscape nationally, regionally, or by urban-rural status, as traditional formats are currently used as the gold standard in food access research. This research utilized publicly available U.S. databases to fill this large literature gap and to provide insight into modes of food access for vulnerable U.S. populations: (1) SNAP Retailer Locator which provides a list of all authorized food stores in the U.S., and; (2) Rural-Urban Continuum Codes (RUCC) that categorize U.S. counties as urban (RUCC 1-3) or rural (RUCC 4-9). Frequencies were determined for the highest occurring food store formats nationally and within two regionally diverse U.S. states – Virginia in the east and California in the west. Store format codes were assigned (e.g., grocery, drug, convenience, mass merchandiser, supercenter, dollar, club, or other). RUCC was applied to investigate state-level differences in urbanity-rurality regarding prevalent food store formats and Chi Square test of independence was used to determine if food store format distributions significantly (p < 0.05) differed by region or rurality. The resulting research sample that represented highly prevalent SNAP-authorized food stores nationally included 41.25% of all SNAP stores in the U.S. (N=257,839), comprised primarily of convenience formats (31.94%) followed by dollar (25.58%), drug (19.24%), traditional (10.87%), supercenter (6.85%), mass merchandiser (1.62%), non-food store or restaurant (1.81%), and club formats (1.09%). Results also indicated that the distribution of prevalent SNAP-authorized formats significantly differed by state. California had a lower proportion of traditional (9.96%) and a higher proportion of drug (28.92%) formats than Virginia- 11.55% and 19.97%, respectively (p < 0.001). Virginia also had a higher proportion of dollar formats (26.11%) when compared to California (10.64%) (p < 0.001). Significant differences were also observed for rurality variables (p < 0.001). Prominently, rural Virginia had a significantly higher proportion of dollar formats (41.71%) when compared to urban Virginia (21.78%) and rural California (21.21%). Non-traditional SNAP-authorized formats are highly prevalent and significantly differ in distribution by U.S. region and rurality. The largest proportional difference was observed for dollar formats where the least nutritious consumer purchases are documented in the literature. Researchers/practitioners should investigate non-traditional food stores at the local level using these research findings and similar applied methodologies to determine how access to various store formats impact obesity prevalence. For example, dollar stores may be prime targets for interventions to enhance nutritious consumer purchases in rural Virginia while targeting drug formats in California may be more appropriate.

Keywords: food access, food store format, nutrition interventions, SNAP consumers

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Authors: Saeed Abbasi, Davood Farsi, Soudabeh Shafiee Ardestani, Neda Valizadeh

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Objectives: Peripheral vertigo is a common complaint of patients who are visited in emergency departments. In our study, we wanted to evaluate the effect of betahistine as an oral drug vs. intravenous diazepam for the treatment of acute peripheral vertigo. We also wanted to see the possibility of substitution of parenteral drug with an oral one with fewer side effects. Materials and Methods: In this randomized, double-blind study, 101 patients were enrolled in the study. The patients were divided in two groups in a double-blind randomized manner. Group A took oral placebo and 10 mg of intravenous diazepam. Group B received 8mg of oral betahistine and intravenous placebo. Patients’ symptoms and signs (Vertigo severity, Nausea, Vomiting, Nistagmus and Gate) were evaluated after 0, 2, 4, 6 hours by emergency physicians and data were collected by a questionnaire. Results: In both groups, there was significant improvement in vertigo (betahistine group P=0.02 and Diazepam group P=0.03). Analysis showed more improvement in vertigo severity after 4 hours of treatment in betahistine group comparing to diazepam group (P=0.02). Nausea and vomiting were significantly lower in patients receiving diazepam after 2 and 6 hours (P=0.02 & P=0.03).No statistically significant differences were found between the groups in nistagmus, equilibrium & vertigo duration. Conclusion: The results of this randomized trial showed that both drugs had acceptable therapeutic effects in peripheral vertigo, although betahistine was significantly more efficacious after 4 hours of drug intake. As for higher nausea and vomiting in betahistine group, physician should consider these side effects before drug prescription.

Keywords: acute peripheral vertigo, betahistine, diazepam, emergency department

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Authors: Salem Abdalla

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Objective: Dipyrone is a widely used, well tolerated analgesic drug which, however, is compromised by agranulocytosis as an adverse effect. Subsequent to no enzymatic hydrolysis, the primary metabolic step is N-demethylation of 4-methylaminoantipyrine (4-MAA) to 4-aminoantipyrine (4-AA). The aim of the present study was to identify the cytochrome P-450 enzyme (CYP) mediating this reaction. Methods: We identified the relevant CYP using virus expressed isolated rat liver microsomes with chemical inhibition studies. The substrate of 4-methylaminantipyrine was employed at six different concentrations (25, 50, 100, 400, 800, and 1200 µmol/l) with varying concentrations of selective inhibitors of CYP1A2 (furafylline, fluvoxamine), CYP3A4 (ketoconazole), CYP2A6 (coumarin), CYP2D6 (quinidine), CYP2C19 (omeprazole, fluvoxamine, tranylcypromine), CYP2C9 (sulfaphenazole), and CYP1A1 (alpha-naphthoflavone). 4-MAA and 4-AA were analyzed by HPLC, and enzyme kinetic parameters (Km and Vmax) were determined by regression (Sigma plot 9.0). Results: The N-demethylation of 4-MAA by microsomes prepared from baculovirus-expressing human CYP was pronounced with CYP2C19. Intrinsic clearances of the most active enzymes were 0.092, 0.027, and 0.026 for the CYP enzymes 2C19, 2D6, and 1A2, respectively. Metabolism by rat liver microsomes was strongly inhibited by omeprazole (IC50 of 0.05). Conclusion: The enzyme CYP2C19 apparently has an important role in N-demethylation of 4-methylaminoantipyrine which should be further analyzed in clinical studies and which may also be interesting concerning the agranulocytosis.

Keywords: dipyrone, 4-methylaminoantipyrine (4-MAA), 4- aminoantipyrine (4-AA), metabolism, human CYP2C19

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Authors: Ahmad Shah Farhat, Anahita Alizadeh Qamsari, Ashraf Mohammadzadeh, Hamid Reza Goldouzian, Ezat Khodashenas

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Introduction: Newborns may be treated with phenobarbital for many reasons. Because in each region, depending on different races and genetic factors, different pharmacokinetic conditions govern the drug. It is essential to control blood levels of certain drugs, especially phenobarbital, and maintain these levels during treatment. Methods: In this study, venous blood was collected from 50 neonates who received intravenous phenobarbital at a loading dose of 20 mg/kg weight and at least three days had passed since the maintenance dose of 5 mg/kg body weight. in 24 hours. and sent to the laboratory. Phenobarbital blood levels were measured, then the results were analyzed descriptively. Results: In this study, the average weight of newborns was 9.93 ± 2.58. The mean blood concentration of phenobarbital, three days after starting the maintenance dose in the group of infants weighing more than 2.5 kg, was 3.33 ± 9.1 micrograms/liter in the group of infants weighing less than 2 kg. and half a kilogram or LBW was 5.9 ± 9.5 micrograms/liter and in the group weighing less than 1.5 kg VLBW was 14.4 ± 15.46 micrograms/liter. There was no significant difference between groups (p>0.05). Three days after starting the maintenance dose in all three groups, the mean blood phenobarbital concentration was 9.86 ± 0.86 micrograms/liter. Conclusion: Blood phenobarbital levels in our newborns are below therapeutic levels, so phenobarbital levels should be evaluated.

Keywords: poisining, neonats, phenobarbital, drug

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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: K. K. Balavenkatraman, B. Bertschi, K. Bigot, A. Grevot, A. Doelemeyer, S. D. Chibout, A. Wolf, F. Pognan, N. Manevski, O. Kretz, P. Swart, K. Litherland, J. Ashton-Chess, B. Ling, R. Wettstein, D. J. Schaefer

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Skin toxicity is poorly detected during preclinical studies, and drug-induced side effects in humans such as rashes, hyperplasia or more serious events like bullous pemphigus or toxic epidermal necrolysis represent an important hurdle for clinical development. In vitro keratinocyte-based epidermal skin models are suitable for the detection of chemical-induced irritancy, but do not recapitulate the biological complexity of full skin and fail to detect potential serious side-effects. Normal healthy skin explants may represent a valuable complementary tool, having the advantage of retaining the full skin architecture and the resident immune cell diversity. This study investigated several conditions for the maintenance of good morphological structure after several days of culture and the retention of phase II metabolism for 24 hours in skin explants in vitro. Human skin samples were collected with informed consent from patients undergoing plastic surgery and immediately transferred and processed in our laboratory by removing the underlying dermal fat. Punch biopsies of 4 mm diameter were cultured in an air-liquid interface using transwell filters. Different cultural conditions such as the effect of calcium, temperature and cultivation media were tested for a period of 14 days and explants were histologically examined after Hematoxylin and Eosin staining. Our results demonstrated that the use of Williams E Medium at 32°C maintained the physiological integrity of the skin for approximately one week. Upon prolonged incubation, the upper layers of the epidermis become thickened and some dead cells are present. Interestingly, these effects were prevented by addition of EGFR inhibitors such as Afatinib or Erlotinib. Phase II metabolism of the skin such as glucuronidation (4-methyl umbeliferone), sulfation (minoxidil), N-acetyltransferase (p-toluidene), catechol methylation (2,3-dehydroxy naphthalene), and glutathione conjugation (chlorodinitro benzene) were analyzed by using LCMS. Our results demonstrated that the human skin explants possess metabolic activity for a period of at least 24 hours for all the substrates tested. A time course for glucuronidation with 4-methyl umbeliferone was performed and a linear correlation was obtained over a period of 24 hours. Longer-term culture studies will indicate the possible evolution of such metabolic activities. In summary, these results demonstrate that human skin explants maintain a normal structure for several days in vitro and are metabolically active for at least the first 24 hours. Hence, with further characterisation, this model may be suitable for the study of drug-induced toxicity.

Keywords: human skin explant, phase II metabolism, epidermal growth factor receptor, toxicity

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Authors: J. P. Lavande, A. V.Chandewar

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Mouth dissolving tablet is the speedily growing and highly accepted drug delivery system. This study was aimed at development of Ketorolac Tromethamine mouth dissolving tablet (MDTs), which can disintegrate or dissolve rapidly once placed in the mouth. Conventional Ketorolac tromethamine tablet requires water to swallow it and has limitation like low disintegration rate, low solubility etc. Ketorolac Tromethamine mouth dissolving tablets (formulation) consist of super-disintegrate like Heat Modified Karaya Gum, Co-treated Heat Modified Agar & Filler microcrystalline cellulose (MCC). The tablets were evaluated for weight variation, friability, hardness, in vitro disintegration time, wetting time, in vitro drug release profile, content uniformity. The obtained results showed that low weight variation, good hardness, acceptable friability, fast wetting time. Tablets in all batches disintegrated within 15-50 sec. The formulation containing superdisintegrants namely heat modified karaya gum and heat modified agar showed better performance in disintegration and drug release profile.

Keywords: mouth dissolving tablet, Ketorolac tromethamine, disintegration time, heat modified karaya gum, co-treated heat modified agar

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Authors: Tao Zhang

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As the competition of all kinds of festival events becomes more and more fierce, more and more event organizers try to design a blended festivalscape by integrating multifaceted environmental cues in order to raise the service quality of festival events and then raise visitors’ satisfaction. As the main type of festival events, food festivals are popular in all over the world. The organizers’ of food festivals also try to mix food with multifaceted environmental cues (e.g., music, stage, light, dance) to design a blended festivalscape. However, until now little studies explore the environmental cues of food festivals and their relationship with visitors’ satisfaction. Therefore, the aim of this study is to ascertain the environmental cues of food festival and their relationship with visitors’ satisfaction by using the blended festivalscape theory. Using convenient sampling method, this study investigated 1,000 food festival visitors in Macau. Factor analysis showed there are mainly six environmental cues (i.e., food, atmosphere, program, staff, facility, and information). All six environmental cues are positively related with visitors’ satisfaction, while the most influential factors are food, atmosphere, and program. This study showed that festival event organizers’ should focus on the topic of their festival event, build festival atmosphere, and create interesting programs in order to design a blended festivalscape and then raise visitors’ satisfaction.

Keywords: environmental cue, event, festival, satisfaction

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Authors: Sahar Iqrar, Malik Adeel Anwar, Zain Akram, Maria Noor

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Introduction: Oral lichen planus is a chronic inflammatory condition of unknown etiology. Oral lichen planus may be related with several other diseases. Grinspan's Syndrome is characterized by a triad of oral lichen planus, hypertension, and diabetes mellitus. Other associations reported in the literature are with chronic liver disease and, with dyslipidemia. The nature of these associations is still not fully understood. Material and methods: Study was conducted in Department of Oral Medicine, Fatima Memorial Hospital College of Medicine and Dentistry, Lahore, Pakistan. A total of n=89 clinically diagnosed patients of oral lichen planus of both gender and all age groups were recruited and detailed history were recorded in the designed performs. Results: A total of n=89 patients were taken with male to female ratio of 3:8 in which 24 were male and 65 females. Mean age was 48.8 ± 13.8 years. Age range of 10-74 years was seen. Among these patients suffering from oral lichen planus, 41.6% (n=37) had a positive history for hypertension with 59.5% (n=22) of these patients were taking different medication for their condition. Whereas Diabetes Mellitus was found in 24.7% (n=22) patients with 72.7% (n=16) of these patients using the hypoglycemic drug (oral or injectable) to control their blood glucose levels. Out of these n=89 lichen planus patients 21.3% had both hypertension and diabetes mellitus (fulfilling the criteria for Grinspan's Syndrome). Out of this Grinspan's Syndrome pool 94.7% (n=19) were taking drug atleast for one of the two conditions. Conclusion: As noticed form the medical history of the patients, most of them were using hypoglycemic drugs for diabetes mellitus and beta blockers, diuretics and calcium channel blockers for hypertension. These drugs are known for lichenoid reaction. Therefore, it should be ruled out at histopathological/ immunological and molecular level whether these patients are suffering from lichen planus or lichenoid drug reaction to truly declare them as patients with Grinspan’s Syndrome.

Keywords: diabetes mellitus, grinspan's syndrome, lichenoid drug reaction, oral lichen planus

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Authors: Pritika Ramharack, Mahmoud E. S. Soliman

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The re-emerging Zika virus is an arthropod-borne virus that has been described to have explosive potential as a worldwide pandemic. The initial transmission of the virus was through a mosquito vector, however, evolving modes of transmission has allowed the spread of the disease over continents. The virus already been linked to irreversible chronic central nervous system (CNS) conditions. The concerns of the scientific and clinical community are the consequences of Zika viral mutations, thus suggesting the urgent need for viral inhibitors. There have been large strides in vaccine development against the virus but there are still no FDA-approved drugs available. Rapid rational drug design and discovery research is fundamental in the production of potent inhibitors against the virus that will not just mask the virus, but destroy it completely. In silico drug design allows for this prompt screening of potential leads, thus decreasing the consumption of precious time and resources. This study demonstrates an optimized and proven screening technique in the discovery of two potential small molecule inhibitors of Zika virus Methyltransferase and RNA-dependent RNA polymerase. This in silico “per-residue energy decomposition pharmacophore” virtual screening approach will be critical in aiding scientists in the discovery of not only effective inhibitors of Zika viral targets, but also a wide range of anti-viral agents.

Keywords: NS5 protein inhibitors, per-residue decomposition, pharmacophore model, virtual screening, Zika virus

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Authors: E. Kilicay, Z. Karahaliloglu, B. Hazer, E. B. Denkbas

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In this study, we have prepared concanavaline A (ConA) functionalized curcumin (CUR) loaded PHBHHx (poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)) nanoparticles as a novel and efficient drug delivery system. CUR is a promising anticancer agent for various cancer types. The aim of this study was to evaluate therapeutic potential of curcumin loaded PHBHHx nanoparticles (CUR-NPs) and concanavaline A conjugated curcumin loaded NPs (ConA-CUR NPs) for ovarian cancer treatment. ConA was covalently connected to the carboxylic group of nanoparticles by EDC/NHS activation method. In the ligand attachment experiment, the binding capacity of ConA on the surface of NPs was found about 90%. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) analysis showed that the prepared nanoparticles were smooth and spherical in shape. The size and zeta potential of prepared NPs were about 228±5 nm and −21.3 mV respectively. ConA-CUR NPs were characterized by FT-IR spectroscopy which confirmed the existence of CUR and ConA in the nanoparticles. The entrapment and loading efficiencies of different polymer/drug weight ratios, 1/0.125 PHBHHx/CUR= 1.25CUR-NPs; 1/0.25 PHBHHx/CUR= 2.5CUR-NPs; 1/0.5 PHBHHx/CUR= 5CUR-NPs, ConA-1.25CUR NPs, ConA-2.5CUR NPs and ConA-5CUR NPs were found to be ≈ 68%-16.8%; 55%-17.7 %; 45%-33.6%; 70%-15.7%; 60%-17%; 51%-30.2% respectively. In vitro drug release showed that the sustained release of curcumin was observed from CUR-NPs and ConA-CUR NPs over a period of 19 days. After binding of ConA, the release rate was slightly increased due to the migration of curcumin to the surface of the nanoparticles and the matrix integrities was decreased because of the conjugation reaction. This functionalized nanoparticles demonstrated high drug loading capacity, sustained drug release profile, and high and long term anticancer efficacy in human cancer cell lines. Anticancer activity of ConA-CUR NPs was proved by MTT assay and reconfirmed by apoptosis and necrosis assay. The anticancer activity of ConA-CUR NPs was measured in ovarian cancer cells (SKOV-3) and the results revealed that the ConA-CUR NPs had better tumor cells decline activity than free curcumin. The nacked nanoparticles have no cytotoxicity against human ovarian carcinoma cells. Thus the developed functionalized nanoformulation could be a promising candidate in cancer therapy.

Keywords: curcumin, curcumin-PHBHHx nanoparticles, concanavalin A, concanavalin A-curcumin PHBHHx nanoparticles, PHBHHx nanoparticles, ovarian cancer cell

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Authors: Pawan Kumar, Dhananjoy Shaw, Manoj Kumar Rathi

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Purpose of the study were to compare between (a) frequencies among the four quartiles of percentile norms of autonomic variables from power events and (b) frequencies among the four quartiles percentile norms of autonomic variables from aerobic events of Indian sportspersons withdrawn from competitive games and sports in regard to number of samples falling in each quartile. The study was conducted on 430 males of 30 to 35 years of age. Based on the nature of game/sports the retired sportspersons were classified into power events (throwers, judo players, wrestlers, short distance swimmers, cricket fast bowlers and power lifters) and aerobic events (long distance runners, long distance swimmers, water polo players). Date was collected using ECG polygraphs. Data were processed and extracted using frequency domain analysis and time domain analysis. Collected data were computed with frequency, percentage of each quartile and finally the frequencies were compared with the chi square analysis. The finding pertaining to norm reference comparison of frequencies among the four quartiles of Indian sportspersons withdrawn from competitive games and sports from (a) power events suggests that frequency distribution in four quartile namely Q1, Q2, Q3, and Q4 are significantly different at .05 level in regard to variables namely, SDNN, Total Power (Absolute Power), HF (Absolute Power), LF (Normalized Power), HF (Normalized Power), LF/HF ratio, deep breathing test, expiratory respiratory ratio, valsalva manoeuvre, hand grip test, cold pressor test and lying to standing test, whereas, insignificantly different at .05 level in regard to variables namely, SDSD, RMSSD, SDANN, NN50 Count, pNN50 Count, LF (Absolute Power) and 30: 15 Ratio (b) aerobic events suggests that frequency distribution in four quartile are significantly different at .05 level in regard to variables namely, SDNN, LF (Normalized Power), HF (Normalized Power), LF/HF ratio, deep breathing test, expiratory respiratory ratio, hand grip test, cold pressor test, lying to standing test and 30: 15 ratio, whereas, insignificantly different at .05 level in regard to variables namely, SDSD, RMSSD. SDANN, NN50 count, pNN50 count, Total Power (Absolute Power), LF(Absolute Power) HF(Absolute Power), and valsalva manoeuvre. The study concluded that comparison of frequencies among the four quartiles of Indian retired sportspersons from power events and aerobic events are different in four quartiles in regard to selected autonomic functions, hence the developed percentile norms are not homogenously distributed across the percentile scale; hence strengthen the percentage distribution towards normal distribution.

Keywords: power, aerobic, absolute power, normalized power

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Authors: Wasantha Pushpakumara Hitihami Mudiyanselage

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Since recent past, Sri Lanka is highly vulnerable to reoccurring climate shocks that severely impact the food security, loss of human & animal lives, destructions of human settlements, displacement of people and damaging properties. Hence, the Government of Sri Lanka has taken important steps towards strengthening legal and institutional arrangements for Disaster Risks management in the country in May 2005. Puttalam administrative district is one of the disaster prone districts in Sri Lanka which constantly face the devastating consequences of the increasing natural disasters annually. Therefore disaster risk management will be a timely intervention in the area to minimize the adverse impacts of the disasters. The few functioning Disaster Risk management networks do not take children’s specific needs and vulnerabilities during emergencies into account. The most affected children and their families were evacuated to the government schools and temples and it was observed that children were left to roaming around as their parents were busy queuing up for relief goods and other priorities. In this sense, VOICE understands that the community has vital role that has to be played in facing challenges of disaster management in the area. During and after the disaster, it was viewed that some children were having psychological disorders which could be impacted negatively to children well–being. Need of child friendly space at emergency is a must action in the area to turn away negative impact coming from the hazards. VOICE with the support of national & international communities have established safer places for the children (Child Centered Spaces – CCS) and their families at emergencies. Village religious venues and schools were selected and equipped with necessary materials to be used for the children at emergency. Materials such as tools, stationeries, play materials, which couldn’t be easily found in surrounding environment, were provided for CCS centers. Village animators, youth and elders were given comprehensive training on Disaster management and their role at CCS. They did the facilitation in keeping children without fear and stress at flooding occurred in 2015 as well as they were able to improve their skills when working with children. Flooding in 2016, the government agencies have taken service of these village animators at early stage of flooding to make all disaster-related recovery actions productively & efficiently. This mechanism is sustained at village level that can be used for disaster events.

Keywords: child centered space, impacts, psychological disorders, village animators

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Authors: Luke McGowan, David Pickernell, Martini Battisti

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In this paper, Adversity Triggers were explored through the lens of Organisational Resilience. Adversity Triggers are contextualized by temporal factors, thus, naturally aligning to Resilience literature. Resilience has been chosen as the theoretical framework as risk management approaches are often not geared towards providing meaningful responses to high-impact, low-probability events. Adversity Triggers and Organisational Resilience both consider temporal factors which enabled investigation of each phase of recovery. A systematic literature was employed to assess previous literature and define further areas of research. The systematic literature review method was chosen to catalogue and identify gaps in current literature.

Keywords: adversity triggers, crisis, extreme events, organisational resilience, resilience

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Authors: Basma Khelfa, Antoine Tordeux, Ibrahima Ba

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We present a descriptive analysis data of lane-changing events in multi-lane roads. The data are provided from The Highway Drone Dataset (HighD), which are microscopic trajectories in highway. This paper describes and analyses the role of the different parameters and their significance. Thanks to HighD data, we aim to find the most frequent reasons that motivate drivers to change lanes. We used the programming language R for the processing of these data. We analyze the involvement and relationship of different variables of each parameter of the ego vehicle and the four vehicles surrounding it, i.e., distance, speed difference, time gap, and acceleration. This was studied according to the class of the vehicle (car or truck), and according to the maneuver it undertook (overtaking or falling back).

Keywords: autonomous driving, physical traffic model, prediction model, statistical learning process

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Authors: Oktira Roka Aji, Maelita R. Moeis, Ihsanawati, Ernawati A. Giri-Rachman

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Globally, tuberculosis (TB) remains a leading cause of death. The emergence of multidrug-resistant strains and extensively drug-resistant strains have become a major public concern. One of the potential candidates for drug target is the cytoplasmic domain of PhoR Histidine Kinase, a part of the Two Component System (TCS) PhoR-PhoP in Mycobacterium tuberculosis (Mtb). TCS PhoR-PhoP relay extracellular signal to control the expression of 114 virulent associated genes in Mtb. The 3D structure of PhoR cytoplasmic domain is needed to screen novel drugs using structure based drug discovery. The PhoR cytoplasmic domain from Mtb H37Rv was overexpressed in E. coli BL21(DE3), then purified using IMAC Ni-NTA Agarose his-tag affinity column and DEAE-ion exchange column chromatography. The molecular weight of the purified protein was estimated to be 37 kDa after SDS-PAGE analysis. This sample was used for pre-crystallization screening by applying sitting drop vapor diffusion method using Natrix (HR2-116) 48 solutions crystal screen kit at 25ºC. Needle-like crystals were observed after the seventh day of incubation in test solution No.47 (0.1 M KCl, 0.01 M MgCl2.6H2O, 0.05 M Tris-Cl pH 8.5, 30% v/v PEG 4000). Further testing is required for confirming the crystal.

Keywords: tuberculosis, two component system, histidine kinase, needle-like crystals

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Authors: Domingos Viegas, Miguel Almeida, Carmen Rocha, Ilda Novo, Yolanda Luna

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Forest fires along the more than 1200km of the Spanish-Portuguese border are more and more frequent, currently achieving around 2000 fire events per year. Some of these events develop to large international wildfire requiring concerted operations based on shared information between the two countries. The fire event of Valencia de Alcantara (2003) causing several fatalities and more than 13000ha burnt, is a reference example of these international events. Currently, Portugal and Spain have a specific cross-border cooperation protocol on wildfires response for a strip of about 30km (15 km for each side). It is recognized by public authorities the successfulness of this collaboration however it is also assumed that this cooperation should include more functionalities such as the development of a common risk information system for transboundary fire events. Since Portuguese and Spanish authorities use different approaches to determine the fire risk indexes inputs and different methodologies to assess the fire risk, sometimes the conjoint firefighting operations are jeopardized since the information is not harmonized and the understanding of the situation by the civil protection agents from both countries is not unique. Thus, a methodology aiming the harmonization of the fire risk calculation and perception by Portuguese and Spanish Civil protection authorities is hereby presented. The final results are presented as well. The fire risk index used in this work is the Canadian Fire Weather Index (FWI), which is based on meteorological data. The FWI is limited on its application as it does not take into account other important factors with great effect on the fire appearance and development. The combination of these factors is very complex since, besides the meteorology, it addresses several parameters of different topics, namely: sociology, topography, vegetation and soil cover. Therefore, the meaning of FWI values is different from region to region, according the specific characteristics of each region. In this work, a methodology for FWI calibration based on the number of fire occurrences and on the burnt area in the transboundary regions of Portugal and Spain, in order to assess the fire risk based on calibrated FWI values, is proposed. As previously mentioned, the cooperative firefighting operations require a common perception of the information shared. Therefore, a common classification of the fire risk for the fire events occurred in the transboundary strip is proposed with the objective of harmonizing this type of information. This work is integrated in the ECHO project SpitFire - Spanish-Portuguese Meteorological Information System for Transboundary Operations in Forest Fires, which aims the development of a web platform for the sharing of information and supporting decision tools to be used in international fire events involving Portugal and Spain.

Keywords: data harmonization, FWI, international collaboration, transboundary wildfires

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Authors: Abhay Asthana, Shally Toshkhani, Gyati Shilakari

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The objective of the present research work is to develop a topical biodegradable dermal patch based formulation to aid accelerated wound healing. It is always better for patient compliance to be able to reduce the frequency of dressings with improved drug delivery and overall therapeutic efficacy. In present study optimized formulation using biodegradable components was obtained evaluating polymers and excipients (HPMC K4M, Ethylcellulose, Povidone, Polyethylene glycol and Gelatin) to impart significant folding endurance, elasticity, and strength. Molten gelatin was used to get a mixture using ethylene glycol. Chitosan dissolved in acidic medium was mixed with stirring to Gelatin mixture. With continued stirring to the mixture Curcumin was added with the aid of DCM and Methanol in an optimized ratio of 60:40 to get homogenous dispersion. Polymers were dispersed with stirring in the final formulation. The mixture was sonicated casted to get the film form. All steps were carried out under strict aseptic conditions. The final formulation was a thin uniformly smooth textured film with dark brown-yellow color. The film was found to have folding endurance was around 20 to 21 times without a crack in an optimized formulation at RT (23°C). The drug content was in range 96 to 102% and it passed the content uniform test. The final moisture content of the optimized formulation film was NMT 9.0%. The films passed stability study conducted at refrigerated conditions (4±0.2°C) and at room temperature (23 ± 2°C) for 30 days. Further, the drug content and texture remained undisturbed with stability study conducted at RT 23±2°C for 45 and 90 days. Percentage cumulative drug release was found to be 80% in 12h and matched the biodegradation rate as tested in vivo with correlation factor R2>0.9. In in vivo study administration of one dose in equivalent quantity per 2 days was applied topically. The data demonstrated a significant improvement with percentage wound contraction in contrast to control and plain drug respectively in given period. The film based formulation developed shows promising results in terms of stability and in vivo performance.

Keywords: wound healing, biodegradable, polymers, patch

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Authors: Rui Teixeira, Alan O’Connor, Maria Nogal

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The statistical theory of extreme events is progressively a topic of growing interest in all the fields of science and engineering. The changes currently experienced by the world, economic and environmental, emphasized the importance of dealing with extreme occurrences with improved accuracy. When it comes to the design of offshore structures, particularly offshore wind turbines, the importance of efficiently characterizing extreme events is of major relevance. Extreme events are commonly characterized by extreme values theory. As an alternative, the accurate modeling of the tails of statistical distributions and the characterization of the low occurrence events can be achieved with the application of the Peak-Over-Threshold (POT) methodology. The POT methodology allows for a more refined fit of the statistical distribution by truncating the data with a minimum value of a predefined threshold u. For mathematically approximating the tail of the empirical statistical distribution the Generalised Pareto is widely used. Although, in the case of the exceedances of significant wave data (H_s) the 2 parameters Weibull and the Exponential distribution, which is a specific case of the Generalised Pareto distribution, are frequently used as an alternative. The Generalized Pareto, despite the existence of practical cases where it is applied, is not completely recognized as the adequate solution to model exceedances over a certain threshold u. References that set the Generalised Pareto distribution as a secondary solution in the case of significant wave data can be identified in the literature. In this framework, the current study intends to tackle the discussion of the application of statistical models to characterize exceedances of wave data. Comparison of the application of the Generalised Pareto, the 2 parameters Weibull and the Exponential distribution are presented for different values of the threshold u. Real wave data obtained in four buoys along the Irish coast was used in the comparative analysis. Results show that the application of the statistical distributions to characterize significant wave data needs to be addressed carefully and in each particular case one of the statistical models mentioned fits better the data than the others. Depending on the value of the threshold u different results are obtained. Other variables of the fit, as the number of points and the estimation of the model parameters, are analyzed and the respective conclusions were drawn. Some guidelines on the application of the POT method are presented. Modeling the tail of the distributions shows to be, for the present case, a highly non-linear task and, due to its growing importance, should be addressed carefully for an efficient estimation of very low occurrence events.

Keywords: extreme events, offshore structures, peak-over-threshold, significant wave data

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Authors: Zahid Iqbal, Ijaz Javed, Riaz Hussain, Ibadullah Jan, Amir Ali Khan

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This study was conducted to investigate the disposition kinetics of ciprofloxacin and calculate its optimal dosage in Pakistani sheep of Lohi breed. Injectable preparation of ciprofloxacin was given intramuscularly to eight sheep at a dose of 5 mg/Kg. Before administration of drug blood sample was drawn from each animal. Post drug administration, blood samples were also drawn at various predetermined time periods. Drug concentration in the blood samples was assessed through high performance liquid chromatograph (HPLC). Data were best described by two compartment open model and different pharmacokinetic (PK) parameters were calculated. Cmax of 1.97 ± 0.15 µg/ml was reached at Tmax of 0.88 ± 0.09 hours. Half life of absorption (t1/2 abs) was observed to be 0.63 ± 0.16 hours while t1/2 α (distribution half life) and t1/2 ß (elimination half life) were found to be 0.46 ± 0.05 and 2.93 ± 0.45 hours, respectively. Vd (apparent volume of distribution) was calculated as 2.89 ± 0.30 L/kg while AUC (area under the curve) was 7.19 ± 0.38 µg.hr/mL and CL (total body clearance) was 0.75 ± 0.04 L/hr/kg. Using these parameters, an optimal intramuscular dosage of ciprofloxacin in adult Lohi sheep was calculated as 21.43 mg/kg, advised to be repeated after 24 hours. From this, we came to the conclusion that calculated dose was much higher than the dose advised by the foreign manufacturer and to avoid antimicrobial resistance, it is advised that this locally investigated dosage regimen should be strictly followed in local sheep.

Keywords: pharmacokinetics, dosage regimen, ciprofloxacin, HPLC, sheep

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Authors: G. Wagner, R. Herrmann

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Cytotoxic platinum compounds play a major role in the chemotherapy of a large number of human cancers. However, due to the severe side effects for the patient and other problems associated with their use, there is a need for the development of more efficient drugs and new methods for their selective delivery to the tumours. One way to achieve the latter could be in the use of nanoparticular substrates that can adsorb or chemically bind the drug. In the cell, the drug is supposed to be slowly released, either by physical desorption or by dissolution of the particle framework. Ideally, the cytotoxic properties of the platinum drug unfold only then, in the cancer cell and over a longer period of time due to the gradual release. In this paper, we report on our first steps in this direction. The binding properties of a series of cytotoxic Pt(II) oxadiazoline compounds to mesoporous silica particles has been studied by NMR and UV/vis spectroscopy. High loadings were achieved when the Pt(II) compound was relatively polar, and has been dissolved in a relatively nonpolar solvent before the silica was added. Typically, 6-10 hours were required for complete equilibration, suggesting the adsorption did not only occur to the outer surface but also to the interior of the pores. The untreated and Pt(II) loaded particles were characterised by C, H, N combustion analysis, BET/BJH nitrogen sorption, electron microscopy (REM and TEM) and EDX. With the latter methods we were able to demonstrate the homogenous distribution of the Pt(II) compound on and in the silica particles, and no Pt(II) bulk precipitate had formed. The in vitro cytotoxicity in a human cancer cell line (HeLa) has been determined for one of the new platinum compounds adsorbed to mesoporous silica particles of different size, and compared with the corresponding compound in solution. The IC50 data are similar in all cases, suggesting that the release of the Pt(II) compound was relatively fast and possibly occurred before the particles reached the cells. Overall, the platinum drug is chemically stable on silica and retained its activity upon prolonged storage.

Keywords: cytotoxicity, mesoporous silica, nanoparticles, platinum compounds

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Authors: Sertac Arslan, Guven Guney, Ayse Ipek Akyuz Unsal, Emre Demir, Buket Demirci

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Purpose: There is little histologic data concerning effects of nasal decongestants on the respiratory tract. We aimed to put forth the effects of nasal decongestants on the trachea and lower airways of rats. Materials and Methods: Four to six months old 60 male rats were randomly categorized into 6 groups. Experimental drugs were applied to the same nostril of rats twice daily for 8 weeks (Xylometazolin, Benzalkolyum, EDTA, Sorbitol and combined drug solutions). We applied normal saline solution (NaCl %0.9) for the control group. In the end, trachea and both lungs were dissected and kept in formaldehyde for histopathologic evaluation. Results: Inflammation and bronchial edema were most common findings. While all rats in sorbitol group had increased numbers of type 2 pneumocytes; 80% of BAC group had increased numbers of type 2 pneumocytes. Spillover of tracheal epithelium was seen mostly in sorbitol, EDTA and combined drug groups (60%, 87.5%, 50% respectively). Bronchial smooth muscle hypertrophy was seen mostly in BAC and EDTA group (70%, 62.5% respectively). The number of goblet cells showed the significant difference between control-combined drug (p=0.025) and control-BAC (p=0.001) groups. Conclusions: Nasal decongestants can cause permanent changes at lower respiratory tract in addition to changes in upper respiratory tract.

Keywords: decongestive agents, xylometazoline, lung, trachea

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Authors: Muhammad Mustaqeem, Musa Kaleem Baloch, Irfan Ullah, Ammarah Luqman, Afshan Ahmad

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Flurbiprofen is one of the most potent nonsteroidal anti-inflammatory drugs. It is widely used for relief of pain in patients suffering from rheumatic diseases, migraine, sore throat and primary dysmenorrhea. However, its aqueous solubility is very low and hinders the skin permeation. Thus, it is imperative to develop such a drug delivery systems which can improve its aqueous solubility and hence improve the skin permeation and therapeutic compliance. Microemulsions have been also proven to increase the cutaneous absorption of lipophilic drugs as compared to conventional vehicles. Micro-emulsion is thermodynamically stable emulsion that has the capacity to ‘hide/solubilize’ water-insoluble molecules within a continuous oil phase. Therefore, flurbiprofen was converted to Easters through chemical reactions with alcohols such as methanol, ethanol, propanol and butanol. The product was further treated with hydrazine to get hydrazide. The solubility of the parent drug Flurbiprofen and the products were solubilized in microemulsions formed using various surfactants like ionic, non-ionic and zwitterions. It has been concluded that the product was more soluble than the parent compound. The biological activities of these were also investigated. The outcome was very promising and the product was more active than the parent compound. It, therefore, concluded that in this way, we can not only enhance the solubility of the drug and increase its bioactivity, but also reduce the risk of stomach cancer.

Keywords: Flurbiprofen, microemulsion, surfactants, hyrazides

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Authors: Tewelde Gebreslassie Gebreanenia, Frie Ayalew Yimam, Seada Hussen Adem

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Patient safety and quality of care are essential goals of health care delivery, but they are often compromised by human errors, system failures, or resource constraints. In a variety of healthcare contexts, artificial intelligence (AI), a quickly developing field, can provide fresh approaches to enhancing patient safety and treatment quality. Artificial Intelligence (AI) has the potential to decrease errors and enhance patient outcomes by carrying out tasks that would typically require human intelligence. These tasks include the detection and prevention of adverse events, monitoring and warning patients and clinicians about changes in vital signs, symptoms, or risks, offering individualized and evidence-based recommendations for diagnosis, treatment, or prevention, and assessing and enhancing the effectiveness of health care systems and services. This study examines the state-of-the-art and potential future applications of AI-based technologies for enhancing patient safety and care quality, as well as the opportunities and problems they present for patients, policymakers, researchers, and healthcare providers. In order to ensure the safe, efficient, and responsible application of AI in healthcare, the paper also addresses the ethical, legal, social, and technical challenges that must be addressed and regulated.

Keywords: artificial intelligence, health care, human intelligence, patient safty, quality of care

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Authors: Abdul Musaweer Habib, Habibul Hasan Mazumder, Saiful Islam, Sohel Sikder, Omar Faruk Sikder

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The plethora of genome sequence information of bacteria in recent times has ushered in many novel strategies for antibacterial drug discovery and facilitated medical science to take up the challenge of the increasing resistance of pathogenic bacteria to current antibiotics. In this study, we adopted subtractive genomics approach to analyze the whole genome sequence of the Fusobacterium nucleatum, a human oral pathogen having association with colorectal cancer. Our study divulged 1499 proteins of Fusobacterium nucleatum, which has no homolog in human genome. These proteins were subjected to screening further by using the Database of Essential Genes (DEG) that resulted in the identification of 32 vitally important proteins for the bacterium. Subsequent analysis of the identified pivotal proteins, using the KEGG Automated Annotation Server (KAAS) resulted in sorting 3 key enzymes of F. nucleatum that may be good candidates as potential drug targets, since they are unique for the bacterium and absent in humans. In addition, we have demonstrated the 3-D structure of these three proteins. Finally, determination of ligand binding sites of the key proteins as well as screening for functional inhibitors that best fitted with the ligands sites were conducted to discover effective novel therapeutic compounds against Fusobacterium nucleatum.

Keywords: colorectal cancer, drug target, Fusobacterium nucleatum, homology modeling, ligands

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Authors: Stijn Horck

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Background: The value of lessons learned from failure increases when these insights can be put to use by those who did not experience the failure. While learning from others has mostly been researched between individuals or teams within the same environment, transferring knowledge from the person who experienced the failure to an outsider comes with extra challenges. As sense-making of failure is an individual process leading to different learning experiences, the potential of lessons learned from failure is highly variable depending on who is transferring the lessons learned. Using an integrated framework of linguistic aspects related to attributional egotism, this study aims to offer a complete explanation of the challenges in transferring lessons learned from failures that are experienced by others. Method: A case study of a failed foundation established to address the information needs for GPs in times of COVID-19 has been used. An overview of failure causes and lessons learned were made through a preliminary analysis of data collected in two phases with metaphoric examples of failure types. This was followed up by individual narrative interviews with the board members who have all experienced the same events to analyse the individual variance of lessons learned through discourse analysis. This research design uses the researcher-as-instrument approach since the recipient of these lessons learned is the author himself. Results: Thirteen causes were given why the foundation has failed, and nine lessons were formulated. Based on the individually emphasized events, the explanation of the failure events mentioned by all or three respondents consisted of more linguistic aspects related to attributional egotism than failure events mentioned by only one or two. Moreover, the learning events mentioned by all or three respondents involved lessons learned that are based on changed insight, while the lessons expressed by only one or two are more based on direct value. Retrospectively, the lessons expressed as a group in the first data collection phase seem to have captured some but not all of the direct value lessons. Conclusion: Individual variance in expressing lessons learned to outsiders can be reduced using metaphoric or analogical explanations from a third party. In line with the attributional egotism theory, individuals separated from a group that has experienced the same failure are more likely to refer to failure causes of which the chances to be contradicted are the smallest. Lastly, this study contributes to the academic literature by demonstrating that the use of linguistic analysis is suitable for investigating the knowledge transfer from lessons learned after failure.

Keywords: failure, discourse analysis, knowledge transfer, attributional egotism

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Authors: Saeed Farhadypour, Majid Azadi, Habibolla Sayyari, Mahmood Mosavi, Shahram Irani, Aliakbar Bidokhti, Omid Alizadeh Choobari, Ziba Hamidi

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In the recent decades, frequencies of dust events have increased significantly in west and south west of Iran. First, a survey on the dust events during the period (1990-2013) is investigated using historical dust data collected at 6 weather stations scattered over west and south-west of Iran. After statistical analysis of the observational data, one of the most severe dust storm event that occurred in the region from 3rd to 6th July 2009, is selected and analyzed. WRF-Chem model is used to simulate the amount of PM10 and how to transport it to the areas. The initial and lateral boundary conditions for model obtained from GFS data with 0.5°×0.5° spatial resolution. In the simulation, two aerosol schemas (GOCART and MADE/SORGAM) with 3 options (chem_opt=106,300 and 303) were evaluated. Results of the statistical analysis of the historical data showed that south west of Iran has high frequency of dust events, so that Bushehr station has the highest frequency between stations and Urmia station has the lowest frequency. Also in the period of 1990 to 2013, the years 2009 and 1998 with the amounts of 3221 and 100 respectively had the highest and lowest dust events and according to the monthly variation, June and July had the highest frequency of dust events and December had the lowest frequency. Besides, model results showed that the MADE / SORGAM scheme has predicted values and trends of PM10 better than the other schemes and has showed the better performance in comparison with the observations. Finally, distribution of PM10 and the wind surface maps obtained from numerical modeling showed that the formation of dust plums formed in Iraq and Syria and also transportation of them to the West and Southwest of Iran. In addition, comparing the MODIS satellite image acquired on 4th July 2009 with model output at the same time showed the good ability of WRF-Chem in simulating spatial distribution of dust.

Keywords: dust storm, MADE/SORGAM scheme, PM10, WRF-Chem

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Authors: Ritu Shitak

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Humans are social mammals, of the primate order. Our biology, behaviour, and pathologies are unique to us. In our desire to understand, reduce solitary confinement one source of information is the many reports of social isolation of other social mammals, especially primates. A behavioural study was conducted in the department of pharmacology at Indira Gandhi Medical College, Shimla in Himachal Pradesh province in India using white albino mice. Different behavioural parameters were observed by using open field, tail suspension, tests for aggressive behaviour and social interactions and the effect of isolation was studied. The results were evaluated and the standard statistics were applied. The said study was done to establish facts that isolation itself impairs social behaviour and can lead to alcohol dependence as well as related drug dependence.

Keywords: social isolation, albino mice, drug dependence, isolation on social behaviour

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