Search results for: critical alarms checklist
1841 Calculation of Secondary Neutron Dose Equivalent in Proton Therapy of Thyroid Gland Using FLUKA Code
Authors: M. R. Akbari, M. Sadeghi, R. Faghihi, M. A. Mosleh-Shirazi, A. R. Khorrami-Moghadam
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Proton radiotherapy (PRT) is becoming an established treatment modality for cancer. The localized tumors, the same as undifferentiated thyroid tumors are insufficiently handled by conventional radiotherapy, while protons would propose the prospect of increasing the tumor dose without exceeding the tolerance of the surrounding healthy tissues. In spite of relatively high advantages in giving localized radiation dose to the tumor region, in proton therapy, secondary neutron production can have significant contribution on integral dose and lessen advantages of this modality contrast to conventional radiotherapy techniques. Furthermore, neutrons have high quality factor, therefore, even a small physical dose can cause considerable biological effects. Measuring of this neutron dose is a very critical step in prediction of secondary cancer incidence. It has been found that FLUKA Monte Carlo code simulations have been used to evaluate dose due to secondaries in proton therapy. In this study, first, by validating simulated proton beam range in water phantom with CSDA range from NIST for the studied proton energy range (34-54 MeV), a proton therapy in thyroid gland cancer was simulated using FLUKA code. Secondary neutron dose equivalent of some organs and tissues after the target volume caused by 34 and 54 MeV proton interactions were calculated in order to evaluate secondary cancer incidence. A multilayer cylindrical neck phantom considering all the layers of neck tissues and a proton beam impinging normally on the phantom were also simulated. Trachea (accompanied by Larynx) had the greatest dose equivalent (1.24×10-1 and 1.45 pSv per primary 34 and 54 MeV protons, respectively) among the simulated tissues after the target volume in the neck region.Keywords: FLUKA code, neutron dose equivalent, proton therapy, thyroid gland
Procedia PDF Downloads 4251840 How Message Framing and Temporal Distance Affect Word of Mouth
Authors: Camille Lacan, Pierre Desmet
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In the crowdfunding model, a campaign succeeds by collecting the funds required over a predefined duration. The success of a CF campaign depends both on the capacity to attract members of the online communities concerned, and on the community members’ involvement in online word-of-mouth recommendations. To maximize the campaign's success probability, project creators (i.e., an organization appealing for financial resources) send messages to contributors to ask them to issue word of mouth. Internet users relay information about projects through Word of Mouth which is defined as “a critical tool for facilitating information diffusion throughout online communities”. The effectiveness of these messages depends on the message framing and the time at which they are sent to contributors (i.e., at the start of the campaign or close to the deadline). This article addresses the following question: What are the effect of message framing and temporal distance on the willingness to share word of mouth? Drawing on Perspectives Theory and Construal Level Theory, this study examines the interplay between message framing (Gains vs. Losses) and temporal distance (message while the deadline is coming vs. far) on intention to share word of mouth. A between-subject experimental design is conducted to test the research model. Results show significant differences between a loss-framed message (lack of benefits if the campaign fails) associated with a short deadline (ending tomorrow) compared to a gain-framed message (benefits if the campaign succeeds) associated with a distant deadline (ending in three months). However, this effect is moderated by the anticipated regret of a campaign failure and the temporal orientation. These moderating effects contribute to specifying the boundary condition of the framing effect. Handling the message framing and the temporal distance are thus the key decisions to influence the willingness to share word of mouth.Keywords: construal levels, crowdfunding, message framing, word of mouth
Procedia PDF Downloads 2521839 Causes of Death in Neuromuscular Disease Patients: 15-Year Experience in a Tertiary Care Hospital
Authors: Po-Ching Chou, Wen-Chen Liang, I. Chen Chen, Jong-Hau Hsu, Yuh-Jyh Jong
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Background:Cardiopulmonary complications seem to cause high morbidity and mortality in patients with neuromuscular diseases (NMD) but so far there is no domestic data reported in Taiwan. We, therefore attempted to analyze the factors to cause the death in NMD patients from our cohort. Methods:From 1998 to 2013, we retrospectively collected the information of the NMD patients treated and followed up in Kaohsiung Medical University Hospital. Forty-two patients with NMD who expired during these fifteen years were enrolled. The medical records of these patients were reviewed and the causes of death and the associated affecting factors were analyzed. Results:Eighteen patients with NMD (mean age=13.3, SD=12.4) with complete medical record and detailed information were finally included in this study, including spinal muscular atrophy (SMA) (n=9, 7/9: type 1), Duchenne muscular dystrophy (n=6), congenital muscular dystrophy (n=1), carnitine acyl-carnitine translocase (CACT) deficiency (n=1) and spinal muscular atrophy with respiratory distress (SMARD)(n=1). The place of death was in ICU (n=11, 61%), emergency room (n=3, 16.6%) or home (n=4, 22.2%). For SMA type 1 patients, most of them (71.4%, 5/7) died in emergency room or home and the other two expired during an ICU admission. The causes of death included acute respiratory failure due to pneumonia (n=13, 72.2 %), ventilator failure or dislocation (n=2, 11.1%), suffocation/choking (n=2, 11.1%), and heart failure with hypertrophic cardiomyopathy (n=1, 5.55%). Among the 15 patients died of respiratory failure or choking, 73.3% of the patients (n=11) received no ventilator care at home. 80% of the patients (n=12) received no cough assist at home. The patient died of cardiomyopathy received no medications for heart failure until the last admission. Conclusion: Respiratory failure and choking are the leading causes of death in NMD patients. Appropriate respiratory support and airway clearance play the critical role to reduce the mortality.Keywords: neuromuscular disease, cause of death, tertiary care hospital, medical sciences
Procedia PDF Downloads 5331838 Modeling and Design of E-mode GaN High Electron Mobility Transistors
Authors: Samson Mil'shtein, Dhawal Asthana, Benjamin Sullivan
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The wide energy gap of GaN is the major parameter justifying the design and fabrication of high-power electronic components made of this material. However, the existence of a piezo-electrics in nature sheet charge at the AlGaN/GaN interface complicates the control of carrier injection into the intrinsic channel of GaN HEMTs (High Electron Mobility Transistors). As a result, most of the transistors created as R&D prototypes and all of the designs used for mass production are D-mode devices which introduce challenges in the design of integrated circuits. This research presents the design and modeling of an E-mode GaN HEMT with a very low turn-on voltage. The proposed device includes two critical elements allowing the transistor to achieve zero conductance across the channel when Vg = 0V. This is accomplished through the inclusion of an extremely thin, 2.5nm intrinsic Ga₀.₇₄Al₀.₂₆N spacer layer. The added spacer layer does not create piezoelectric strain but rather elastically follows the variations of the crystal structure of the adjacent GaN channel. The second important factor is the design of a gate metal with a high work function. The use of a metal gate with a work function (Ni in this research) greater than 5.3eV positioned on top of n-type doped (Nd=10¹⁷cm⁻³) Ga₀.₇₄Al₀.₂₆N creates the necessary built-in potential, which controls the injection of electrons into the intrinsic channel as the gate voltage is increased. The 5µm long transistor with a 0.18µm long gate and a channel width of 30µm operate at Vd=10V. At Vg =1V, the device reaches the maximum drain current of 0.6mA, which indicates a high current density. The presented device is operational at frequencies greater than 10GHz and exhibits a stable transconductance over the full range of operational gate voltages.Keywords: compound semiconductors, device modeling, enhancement mode HEMT, gallium nitride
Procedia PDF Downloads 2611837 Academic Success, Problem-Based Learning and the Middleman: The Community Voice
Authors: Isabel Medina, Mario Duran
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Although Problem-based learning provides students with multiple opportunities for rigorous instructional experiences in which students are challenged to address problems in the community; there are still gaps in connecting community leaders to the PBL process. At a south Texas high school, community participation serves as an integral component of the PBL process. Problem-based learning (PBL) has recently gained momentum due to the increase in global communities that value collaboration and critical thinking. As an instructional approach, PBL engages high school students in meaningful learning experiences. Furthermore, PBL focuses on providing students with a connection to real-world situations that require effective peer collaboration. For PBL leaders, providing students with a meaningful process is as important as the final PBL outcome. To achieve this goal, STEM high school strategically created a space for community involvement to be woven within the PBL fabric. This study examines the impact community members had on PBL students attending a STEM high school in South Texas. At STEM High School, community members represent a support system that works through the PBL process to ensure students receive real-life mentoring from business and industry leaders situated in the community. A phenomenological study using a semi-structured approach was used to collect data about students’ perception of community involvement within the PBL process for one South Texas high school. In our proposed presentation, we will discuss how community involvement in the PBL process academically impacted the educational experience of high school students at STEM high school. We address the instructional concerns PBL critics have with the lack of direct instruction, by providing a representation of how STEM high school utilizes community members to assist in impacting the academic experience of students.Keywords: phenomenological, STEM education, student engagement, community involvement
Procedia PDF Downloads 911836 A Multimodal Measurement Approach Using Narratives and Eye Tracking to Investigate Visual Behaviour in Perceiving Naturalistic and Urban Environments
Authors: Khizar Z. Choudhrya, Richard Coles, Salman Qureshi, Robert Ashford, Salim Khan, Rabia R. Mir
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Abstract: The majority of existing landscape research has been derived by conducting heuristic evaluations, without having empirical insight of real participant visual response. In this research, a modern multimodal measurement approach (using narratives and eye tracking) was applied to investigate visual behaviour in perceiving naturalistic and urban environments. This research is unique in exploring gaze behaviour on environmental images possessing different levels of saliency. Eye behaviour is predominantly attracted by salient locations. The concept of methodology of this research on naturalistic and urban environments is drawn from the approaches in market research. Borrowing methodologies from market research that examine visual responses and qualities provided a critical and hitherto unexplored approach. This research has been conducted by using mixed methodological quantitative and qualitative approaches. On the whole, the results of this research corroborated existing landscape research findings, but they also identified potential refinements. The research contributes both methodologically and empirically to human-environment interaction (HEI). This study focused on initial impressions of environmental images with the help of eye tracking. Taking under consideration the importance of the image, this study explored the factors that influence initial fixations in relation to expectations and preferences. In terms of key findings of this research it is noticed that each participant has his own unique navigation style while surfing through different elements of landscape images. This individual navigation style is given the name of ‘visual signature’. This study adds the necessary clarity that would complete the picture and bring an insight for future landscape researchers.Keywords: human-environment interaction (HEI), multimodal measurement, narratives, eye tracking
Procedia PDF Downloads 3391835 Deconstructing the Niger-Delta Crises: In Esiaba Irobi's Cemetery Road and Hangmen Also Die
Authors: Chukwukelue Uzodinma Umenyilorah
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The history of the crises in Niger-Delta is readily traceable to the post-colonial oil boom of the early 70s. Prior to this time, it was widely believed that the people of Niger-Delta; especially those in the present day Rivers, Delta and Bayelsa States enjoyed a peaceful coexistence pretty much as the rest of Nigerians. In the early 70s however, crude oil was discovered in commercial quantities in these areas and tranquility has become a far cry over the years ever since then. First, a number of multi-national oil explorers moved into the Niger-Delta for business, and then certain conditions resulted in sundry instances of oil spillage, which caused a lot of environmental damage, destroying nearly all of the people’s sources of livelihood. The result was a multiple chain reaction ranging from incessant agitations from the natives to institutionalized dialogue between the oil business owners, the natives and the government, and then to a proposition of compensation packages for the affected communities. The said compensation, which was meant to bring peace seem to have brought even more crises instead. Corruption and greed crept in, money changed hands, suffering increased and so was the agitation from the people. The whole turn of events gradually snowballed into the formation of various militant groups who are now fingered as responsible for the sundry cases of violence in the Niger-Delta. The oil boom can, therefore, be said to be the immediate cause of the Niger-Delta crises, but there are other remote causes as well; including poverty, neglect and illiteracy to mention but a few. This study is therefore aimed at examining the various reasons behind the seemingly unending crises in the Niger-Delta. It will also take a critical look at the roles played by the various parties in the Niger-Delta crises from the 70s to date; as well as the various human and environmental devastations done in the area with a view to making informed suggestions on how to stop further damage and start fixing that, which is already done. Esiaba Irobi’s Cemetery Road and Hangmen Also Die seem to vividly capture the realities of the Niger-Delta situation, and shall, therefore, be reviewed in this study.Keywords: corruption, Niger-delta, oil boom, post-colonial
Procedia PDF Downloads 3141834 Embracing Complex Femininity: A Comparative Analysis of the Representation of Female Sexuality in John Webster and William Faulkner
Authors: Elisabeth Pedersen
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Representations and interpretations of womanhood and female sexualities bring forth various questions regarding gender norms, and the implications of these norms, which are permeating and repetitive within various societies. Literature is one form of media which provides the space to represent and interpret women, their bodies, and sexualities, and also reveals the power of language as an affective and affected force. As literature allows an opportunity to explore history and the representations of gender, power dynamics, and sexuality through historical contexts, this paper uses engaged theory through a comparative analysis of two work of literature, The Duchess of Malfi by John Wester, and The Sound and the Fury by William Faulkner. These novels span across space and time, which lends to the theory that repetitive tropes of womanhood and female sexuality in literature are influenced by and have an influence on the hegemonic social order throughout history. It analyzes how the representation of the dichotomy of male chivalry and honor, and female purity are disputed and questioned when a woman is portrayed as sexually emancipated, and explores the historical context in which these works were written to examine how socioeconomic events challenged the hegemonic social order. The analysis looks at how stereotypical ideals of womanhood and manhood have damaging implications on women, as the structure of society provides more privilege and power to men than to women, thus creating a double standard for men and women in regards to sexuality, sexual expression, and rights to sexual desire. This comparative analysis reveals how strict gender norms are permeating and have negative consequences. However, re-reading stories through a critical lens can provide an opportunity to challenge the repetitive tropes of female sexuality, and thus lead to the embrace of the complexity of female sexuality and expression.Keywords: femininity, literature, representation, sexuality
Procedia PDF Downloads 3591833 The Significant of Effective Leadership on Management Growth and Survival: A Case Study of Bunato Limited Company, Ring Road Ibadan
Authors: A. S. Adegoke, O. N. Popoola
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The central purpose of management in any organization is that of coordinating the efforts of people towards the achievement of its goal. Effective and productive management is the function of leadership. Leadership plays a critical role in helping groups, organizations and societies to achieve their goals. Factors considered to make leadership to be effective are intelligence, social maturity, inner motivation and achievement drives and lastly, human relations attitudes. The factors affecting leadership style and effectiveness were examined. Also, the study examined which of the various leadership style best befits an organization and discussed the ways in which the style was determined. In order to meet the objectives of this study, different types of methods of data gathering were carried out. The methods include data from primary and secondary sources. The primary sources include personal interview, personal observation, and questionnaire while data from secondary sources were derived from various books, journal write up and other documentary records. Data were collected from respondents through questionnaire, and the field research carried out through oral interview to test each of the related hypotheses. From the data analysed it was determined that 45% strongly agreed that leadership traits are inborn not acquired and 28.3% agreed that leadership traits are inborn, while 11.7% and 10% strongly disagreed and disagreed respectively and 5% were undecided. 48.4% strongly agreed, and 43.3% agreed that environmental factors determined the appropriate style of leadership to be employed while 3.3% strongly disagreed, 1.7% disagreed and 3.3% were undecided. From the study, no single style of leadership is appropriate in any situation instead of concentrating on single leadership style; leader can vary approaches depending on forces in the leaders, characteristic of the subordinates, situational forces of the organization, lastly the expectations and behaviour of superior.Keywords: hypothesis, leadership, management, organization
Procedia PDF Downloads 1441832 Development of a Multi-Locus DNA Metabarcoding Method for Endangered Animal Species Identification
Authors: Meimei Shi
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Objectives: The identification of endangered species, especially simultaneous detection of multiple species in complex samples, plays a critical role in alleged wildlife crime incidents and prevents illegal trade. This study was to develop a multi-locus DNA metabarcoding method for endangered animal species identification. Methods: Several pairs of universal primers were designed according to the mitochondria conserved gene regions. Experimental mixtures were artificially prepared by mixing well-defined species, including endangered species, e.g., forest musk, bear, tiger, pangolin, and sika deer. The artificial samples were prepared with 1-16 well-characterized species at 1% to 100% DNA concentrations. After multiplex-PCR amplification and parameter modification, the amplified products were analyzed by capillary electrophoresis and used for NGS library preparation. The DNA metabarcoding was carried out based on Illumina MiSeq amplicon sequencing. The data was processed with quality trimming, reads filtering, and OTU clustering; representative sequences were blasted using BLASTn. Results: According to the parameter modification and multiplex-PCR amplification results, five primer sets targeting COI, Cytb, 12S, and 16S, respectively, were selected as the NGS library amplification primer panel. High-throughput sequencing data analysis showed that the established multi-locus DNA metabarcoding method was sensitive and could accurately identify all species in artificial mixtures, including endangered animal species Moschus berezovskii, Ursus thibetanus, Panthera tigris, Manis pentadactyla, Cervus nippon at 1% (DNA concentration). In conclusion, the established species identification method provides technical support for customs and forensic scientists to prevent the illegal trade of endangered animals and their products.Keywords: DNA metabarcoding, endangered animal species, mitochondria nucleic acid, multi-locus
Procedia PDF Downloads 1401831 Aberrant Genome‐Wide DNA Methylation Profiles of Peripheral Blood Mononuclear Cells from Patients Hospitalized with COVID-19
Authors: Inam Ridha, Christine L. Kuryla, Madhuranga Thilakasiri Madugoda Ralalage Don, Norman J. Kleiman, Yunro Chung, Jin Park, Vel Murugan, Joshua LaBaer
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To date, more than 275 million people worldwide have been diagnosed with COVID-19 and the rapid spread of the omicron variant suggests many millions more will soon become infected. Many infections are asymptomatic, while others result in mild to moderate illness. Unfortunately, some infected individuals exhibit more serious symptoms including respiratory distress, thrombosis, cardiovascular disease, multi-organ failure, cognitive difficulties, and, in roughly 2% of cases, death. Studies indicate other coronaviruses can alter the host cell's epigenetic profile and lead to alterations in the immune response. To better understand the mechanism(s) by which SARS-CoV-2 infection causes serious illness, DNA methylation profiles in peripheral blood mononuclear cells (PBMCs) from 90 hospitalized severely ill COVID-19 patients were compared to profiles from uninfected control subjects. Exploratory epigenome-wide DNA methylation analyses were performed using multiplexed methylated DNA immunoprecipitation (MeDIP) followed by pathway enrichment analysis. The findings demonstrated significant DNA methylation changes in infected individuals as compared to uninfected controls. Pathway analysis indicated that apoptosis, cell cycle control, Toll-like receptors (TLR), cytokine interactions, and T cell differentiation were among the most affected metabolic processes. In addition, changes in specific gene methylation were compared to SARS-CoV-2 induced changes in RNA expression using published RNA-seq data from 3 patients with severe COVID-19. These findings demonstrate significant correlations between differentially methylated and differentially expressed genes in a number of critical pathways.Keywords: COVID19, epigenetics, DNA mathylation, viral infection
Procedia PDF Downloads 1811830 Genetic Assessment of The Managed Gharial Population In The Girwa River, India
Authors: Surya Prasad Sharma, Suyash Katdare, Syed Ainul Hussain
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Human-induced factors contributed to the population decline of crocodylians in India which became evident by the mid-20th century when authorities forewarned the extinction risk for the crocodile and proposed regulation in the crocodile trade. The proposed action led to the enactment of national and international wildlife regulations to prohibit the trade-in of crocodile skins and parts. Subsequently, conservation translocation programs were initiated to restore the species in the wild through a 'head-start' approach. In India, the crocodile conservation program, which began in the early 1970s, has been one of India's longest-running conservation initiatives. The gharial (Gavialis gangeticus) population has benefitted, and the gharial number increased rapidly owing to these efforts. The immediate risk of extinction was averted as the gharial has recovered due to decades-long cumulative conservation efforts, the consideration of the genetic for monitoring the recovery of the recovered populations is still lacking. Hence, we assessed the genetic diversity of the Girwa gharial population in India using six polymorphic nuclear microsatellites loci and mitochondrial control region. The number of alleles per loci ranged between 2 to 5, and the allelic richness (Ar) was 2.67 ± 0.49, and the observed (Ho) and expected (He) heterozygosities were 0.42 ± 0.08 and 0.42 ± 0.09, respectively. The M-ratio yielded a value of (0.41 ± 0.16) lower than critical M, suggesting a genetic bottleneck in the Girwa population. We observed more mitochondrial control region haplotypes in the Girwa population than previously reported in the largest gharial population in the Chambal River. Overall, our study indicates that genetic diversity remains low despite the recovery in the Girwa population. Hence, we recommend a range-wide genetic assessment of gharial populations using high-throughput techniques to identify the source population and plan future translocation programs.Keywords: conservation translocation, recovery, crocodile, bottleneck
Procedia PDF Downloads 1101829 Analysis of Rural Roads in Developing Countries Using Principal Component Analysis and Simple Average Technique in the Development of a Road Safety Performance Index
Authors: Muhammad Tufail, Jawad Hussain, Hammad Hussain, Imran Hafeez, Naveed Ahmad
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Road safety performance index is a composite index which combines various indicators of road safety into single number. Development of a road safety performance index using appropriate safety performance indicators is essential to enhance road safety. However, a road safety performance index in developing countries has not been given as much priority as needed. The primary objective of this research is to develop a general Road Safety Performance Index (RSPI) for developing countries based on the facility as well as behavior of road user. The secondary objectives include finding the critical inputs in the RSPI and finding the better method of making the index. In this study, the RSPI is developed by selecting four main safety performance indicators i.e., protective system (seat belt, helmet etc.), road (road width, signalized intersections, number of lanes, speed limit), number of pedestrians, and number of vehicles. Data on these four safety performance indicators were collected using observation survey on a 20 km road section of the National Highway N-125 road Taxila, Pakistan. For the development of this composite index, two methods are used: a) Principal Component Analysis (PCA) and b) Equal Weighting (EW) method. PCA is used for extraction, weighting, and linear aggregation of indicators to obtain a single value. An individual index score was calculated for each road section by multiplication of weights and standardized values of each safety performance indicator. However, Simple Average technique was used for weighting and linear aggregation of indicators to develop a RSPI. The road sections are ranked according to RSPI scores using both methods. The two weighting methods are compared, and the PCA method is found to be much more reliable than the Simple Average Technique.Keywords: indicators, aggregation, principle component analysis, weighting, index score
Procedia PDF Downloads 1581828 Chromatographic Preparation and Performance on Zinc Ion Imprinted Monolithic Column and Its Adsorption Property
Authors: X. Han, S. Duan, C. Liu, C. Zhou, W. Zhu, L. Kong
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The ionic imprinting technique refers to the three-dimensional rigid structure with the fixed pore sizes, which was formed by the binding interactions of ions and functional monomers and used ions as the template, it has a high level of recognition to the ionic template. The preparation of monolithic column by the in-situ polymerization need to put the compound of template, functional monomers, cross-linking agent and initiating agent into the solution, dissolve it and inject to the column tube, and then the compound will have a polymerization reaction at a certain temperature, after the synthetic reaction, we washed out the unread template and solution. The monolithic columns are easy to prepare, low consumption and cost-effective with fast mass transfer, besides, they have many chemical functions. But the monolithic columns have some problems in the practical application, such as low-efficiency, quantitative analysis cannot be performed accurately because of the peak shape is wide and has tailing phenomena; the choice of polymerization systems is limited and the lack of theoretical foundations. Thus the optimization of components and preparation methods is an important research direction. During the preparation of ionic imprinted monolithic columns, pore-forming agent can make the polymer generate the porous structure, which can influence the physical properties of polymer, what’ s more, it can directly decide the stability and selectivity of polymerization reaction. The compounds generated in the pre-polymerization reaction could directly decide the identification and screening capabilities of imprinted polymer; thus the choice of pore-forming agent is quite critical in the preparation of imprinted monolithic columns. This article mainly focuses on the research that when using different pore-forming agents, the impact of zinc ion imprinted monolithic column on the enrichment performance of zinc ion.Keywords: high performance liquid chromatography (HPLC), ionic imprinting, monolithic column, pore-forming agent
Procedia PDF Downloads 2141827 Dermoscopy Compliance: Improving Melanoma Detection Pathways Through Quality Improvement
Authors: Max Butler
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Melanoma accounts for 80% of skin cancer-related deaths globally. The poor prognosis and increasing incidence of melanoma impose a significant burden on global healthcare systems. Early detection, precise diagnosis, and preventative strategies are critical to improving patient outcomes. Dermoscopy is the gold standard for specialist assessments of pigmented skin lesions, as it can differentiate between benign and malignant growths with greater accuracy than visual inspection. In the United Kingdom, guidelines from the National Institute of Clinical Excellence (NICE) state dermoscopy should be used in all specialist assessments of pigmented skin lesions. Compliance with this guideline is low, resulting in missed and delayed melanoma diagnoses. To address this problem, a quality improvement project was initiated at Buckinghamshire Healthcare Trust (BHT) within the plastic surgery department. The target group was a trainee and consultant plastic surgeons conducting outpatient skin cancer clinics. Analysis of clinic documentation over a one-month period found that only 62% (38/61) of patients referred with pigmented skin lesions were examined using dermoscopy. To increase dermoscopy rates, teaching was delivered to the department highlighting national guidelines and the evidence base for dermoscopic examination. In addition, clinic paperwork was redesigned to include a text box for dermoscopic examination. Reauditing after the intervention found a significant increase in dermoscopy rates (52/61, p = 0.014). In conclusion, implementing a quality improvement project with targeted teaching and documentation template templates successfully increased dermoscopy rates. This is a promising step toward improving early melanoma detection and patient outcomes.Keywords: melanoma, dermoscopy, plastic surgery, quality improvement
Procedia PDF Downloads 701826 Redirection of Cytokine Production Patterns by Dydrogesterone, an Orally-Administered Progestogen
Authors: Raj Raghupathy
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Recurrent Spontaneous Miscarriage (RSM) is a common form of pregnancy loss, 50% of which are due to ‘unexplained’ causes. Evidence exists to suggest that RSM may be caused by immunologic factors such as cytokines which are critical molecules of the immune system, with an impressive array of capabilities. An association appears to exist between Th2-type reactivity (mediated by Th2 or anti-inflammatory cytokines) and normal, successful pregnancy, and between unexplained RSM and Th1 cytokine dominance. If pro-inflammatory cytokines are indeed associated with pregnancy loss, the suppression of these cytokines, and thus the ‘redirection’ of maternal reactivity, may help prevent cytokine-mediated pregnancy loss. The objective of this study was to explore the possibility of modulating cytokine production using Dydrogesterone (Duphaston®), an orally-administered progestogen. Peripheral blood mononuclear cells from 34 women with a history of at least 3 unexplained recurrent miscarriages were stimulated in vitro with a mitogen (to elicit cytokine production) in the presence and absence of dydrogesterone. Levels of selected pro- and anti-inflammatory cytokines produced by peripheral blood mononuclear cells were measured after exposure to these progestogens. Dydrogesterone down-regulates the production of pro-inflammatory cytokines and up-regulates the production of anti-inflammatory cytokines. The ratios of Th2 to Th1 cytokines are markedly elevated in the presence of dydrogesterone, indicating a shift from potentially harmful maternal Th1 reactivity to a more pregnancy-conducive Th2 profile. We used a progesterone receptor antagonist to show that this cytokine-modulating effect of dydrogesterone is mediated via the progesterone receptor. Dydrogesterone also induces the production of the Progesterone-Induced Blocking Factor (PIBF); lymphocytes exposed to PIBF produce higher levels of Th2 cytokines, affecting a Th1 → Th2 cytokine shift which could be favourable to the success of pregnancy. We conclude that modulation of maternal cytokine production profiles is possible with dydrogesterone which has the merits that it can be administered orally and that it is safe.Keywords: cytokines, dydrogesterone, progesterone, recurrent spontaneous miscarriage
Procedia PDF Downloads 2891825 Indian Art Education and Career Opportunities: A Critical Analysis on Commercial Art
Authors: Pooja Jain
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Art education is often ignored in syllabus of developing countries like India and in educational planning for development but now days Indian Art with a global recognition is becoming an integral part of the education at all levels. The term art, widely used in all parts of the modern world, carried varied significance in India as its meaning was continuously being extended, covering the many varieties of creative expression such as painting, sculpture, commercial art, design, poetry, music, dance, and architecture. Over the last 100 years Indian artists of all forms have evolved a wide variety of expressive styles. With the recommendations and initiatives by Government of India, Art Education has subsequently gained pace at the school level as a mandatory subject for all making a path way for students with a creative bend of mind. This paper investigates curriculum in various schools of the country at secondary and senior secondary levels along with some eminent institutions running the program. Findings depicted the role of art education and justified its importance primarily with commercial art being perceived to be essential for students learning skills for economic gain in their career ahead. With so many art colleges spread across India, emerging artists and designers are being trained and are creating art of infinite variety and style and have opened up many career avenues. Commercial Art being a plethora of artistic expressions has confidently come of age wherein a creative perception is mixed with an introspective imagination to bring out multi faceted career options with a significant future enveloped in art. Visual arts in education thus is an expanding field of result assured research.
Keywords: modern art, commercial art, introspective imagination, career
Procedia PDF Downloads 1901824 Carbon Footprint of Road Project for Sustainable Development: Lessons Learnt from Traffic Management of a Developing Urban Centre
Authors: Sajjad Shukur Ullah, Syed Shujaa Safdar Gardezi
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Road infrastructure plays a vital role in the economic activities of any economy. Besides derived benefits from these facilities, the utilization of extensive energy resources, fuels, and materials results in a negative impact on the environment in terms of carbon footprint; carbon footprint is the overall amount of greenhouse gas (GHG) generated from any action. However, this aspect of environmental impact from road structure is not seriously considered during such developments, thus undermining a critical factor of sustainable development, which usually remains unaddressed, especially in developing countries. The current work investigates the carbon footprint impact of a small road project (0.8 km, dual carriageway) initiated for traffic management in an urban centre. Life cycle assessment (LCA) with boundary conditions of cradle to the site has been adopted. The only construction phase of the life cycle has been assessed at this stage. An impact of 10 ktons-CO2 (6260 ton-CO2/km) has been assessed. The rigid pavement dominated the contributions as compared to a flexible component. Among the structural elements, the underpass works shared the major portion. Among the materials, the concrete and steel utilized for various structural elements resulted in more than 90% of the impact. The earth-moving equipment was dominant in operational carbon. The results have highlighted that road infrastructure projects pose serious threats to the environment during their construction and which need to be considered during the approval stages. This work provides a guideline for supporting sustainable development that could only be ensured when such endeavours are properly assessed by industry professionals and decide various alternative environmental conscious solutions for the future.Keywords: construction waste management, kiloton, life cycle assessment, rigid pavement
Procedia PDF Downloads 1001823 Slope Stability Analysis and Evaluation of Road Cut Slope in Case of Goro to Abagada Road, Adama
Authors: Ezedin Geta Seid
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Slope failures are among the common geo-environmental natural hazards in the hilly and mountainous terrain of the world causing damages to human life and destruction of infrastructures. In Ethiopia, the demand for the construction of infrastructures, especially highways and railways, has increased to connect the developmental centers. However, the failure of roadside slopes formed due to the difficulty of geographical locations is the major difficulty for this development. As a result, a comprehensive site-specific investigation of destabilizing agents and a suitable selection of slope profiles are needed during design. Hence, this study emphasized the stability analysis and performance evaluation of slope profiles (single slope, multi-slope, and benched slope). The analysis was conducted for static and dynamic loading conditions using limit equilibrium (slide software) and finite element method (Praxis software). The analysis results in selected critical sections show that the slope is marginally stable, with FS varying from 1.2 to 1.5 in static conditions, and unstable with FS below 1 in dynamic conditions. From the comparison of analysis methods, the finite element method provides more valuable information about the failure surface of a slope than limit equilibrium analysis. Performance evaluation of geometric profiles shows that geometric modification provides better and more economical slope stability. Benching provides significant stability for cut slopes (i.e., the use of 2m and 3m bench improves the factor of safety by 7.5% and 12% from a single slope profile). The method is more effective on steep slopes. Similarly, the use of a multi-slope profile improves the stability of the slope in stratified soil with varied strength. The performance is more significant when it is used in combination with benches. The study also recommends drainage control and slope reinforcement as a remedial measure for cut slopes.Keywords: slope failure, slope profile, bench slope, multi slope
Procedia PDF Downloads 321822 The Effects of Green Logistics Management Practices on Sustainability Performance in Nigeria
Authors: Ozoemelam Ikechukwu Lazarus, Nizamuddin B. Zainuddi, Abdul Kafi
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Numerous studies have been carried out on Green Logistics Management Practices (GLMPs) across the globe. The study on the practices and performance of green chain practices in Africa in particular has not gained enough scholarly attention. Again, the majority of supply chain sustainability research being conducted focus on environmental sustainability. Logistics has been a major cause of supply chain resource waste and environmental damage. Many sectors of the economy that engage in logistical operations significantly rely on vehicles, which emit pollutants into the environment. Due to urbanization and industrialization, the logistical operations of manufacturing companies represent a serious hazard to the society and human life, making the sector one of the fastest expanding in the world today. Logistics companies are faced with numerous difficulties when attempting to implement logistics practices along their supply chains. In Nigeria, manufacturing companies aspire to implement reverse logistics in response to stakeholders’ requirements to reduce negative environmental consequences. However, implementing this is impeded by a criteria framework, and necessitates the careful analysis of how such criteria interact with each other in the presence of uncertainty. This study integrates most of the green logistics management practices (GLMPs) into the Nigerian firms to improve generalizability, and credibility. It examines the effect of Green Logistics Management Practices on environmental performance, social performance, market performance, and financial performance in the logistics industries. It seeks to identify the critical success factors in order to develop a model that incorporates different factors from the perspectives of the technology, organization, human and environment to inform the adoption and use of technologies for logistics supply chain social sustainability in Nigeria. It uses exploratory research approach to collect and analyse the data.Keywords: logistics, management, sustainability, environment, operations
Procedia PDF Downloads 811821 Computational Fluid Dynamics Simulation of a Boiler Outlet Header Constructed of Inconel Alloy 740H
Authors: Sherman Ho, Ahmed Cherif Megri
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Headers play a critical role in conveying steam to regulate heating system temperatures. While various materials like steel grades 91 and 92 have been traditionally used for pipes, this research proposes the use of a robust and innovative material, INCONEL Alloy 740H. Boilers in power plant configurations are exposed to cycling conditions due to factors such as daily, seasonal, and yearly variations in weather. These cycling conditions can lead to the deterioration of headers, which are vital components with intricate geometries. Header failures result in substantial financial losses from repair costs and power plant shutdowns, along with significant public inconveniences such as the loss of heating and hot water. To address this issue and seek solutions, a mechanical analysis, as well as a structural analysis, are recommended. Transient analysis to predict heat transfer conditions is of paramount importance, as the direction of heat transfer within the header walls and the passing steam can vary based on the location of interest, load, and operating conditions. The geometry and material of the header are also crucial design factors, and the choice of pipe material depends on its usage. In this context, the heat transfer coefficient plays a vital role in header design and analysis. This research employs ANSYS Fluent, a numerical simulation program, to understand header behavior, predict heat transfer, and analyze mechanical phenomena within the header. Transient simulations are conducted to investigate parameters like heat transfer coefficient, pressure loss coefficients, and heat flux, with the results used to optimize header design.Keywords: CFD, header, power plant, heat transfer coefficient, simulation using experimental data
Procedia PDF Downloads 661820 Adhesive Bonded Joints Characterization and Crack Propagation in Composite Materials under Cyclic Impact Fatigue and Constant Amplitude Fatigue Loadings
Authors: Andres Bautista, Alicia Porras, Juan P. Casas, Maribel Silva
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The Colombian aeronautical industry has stimulated research in the mechanical behavior of materials under different loading conditions aircrafts are generally exposed during its operation. The Calima T-90 is the first military aircraft built in the country, used for primary flight training of Colombian Air Force Pilots, therefore, it may be exposed to adverse operating situations such as hard landings which cause impact loads on the aircraft that might produce the impact fatigue phenomenon. The Calima T-90 structure is mainly manufactured by composites materials generating assemblies and subassemblies of different components of it. The main method of bonding these components is by using adhesive joints. Each type of adhesive bond must be studied on its own since its performance depends on the conditions of the manufacturing process and operating characteristics. This study aims to characterize the typical adhesive joints of the aircraft under usual loads. To this purpose, the evaluation of the effect of adhesive thickness on the mechanical performance of the joint under quasi-static loading conditions, constant amplitude fatigue and cyclic impact fatigue using single lap-joint specimens will be performed. Additionally, using a double cantilever beam specimen, the influence of the thickness of the adhesive on the crack growth rate for mode I delamination failure, as a function of the critical energy release rate will be determined. Finally, an analysis of the fracture surface of the test specimens considering the mechanical interaction between the substrate (composite) and the adhesive, provide insights into the magnitude of the damage, the type of failure mechanism that occurs and its correlation with the way crack propagates under the proposed loading conditions.Keywords: adhesive, composites, crack propagation, fatigue
Procedia PDF Downloads 2041819 Galvinising Higher Education Institutions as Creative, Humanised and Innovative Environments
Authors: A. Martins, I. Martins, O. Pereira
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The purpose of this research is to focus on the importance of distributed leadership in universities and Higher Education Institutions (HEIs). The research question is whether there a significant finding in self-reported ratings of leadership styles of those respondents that are studying management. The study aims to further discover whether students are encouraged to become responsible and proactive citizens, to develop their skills set, specifically shared leadership and higher-level skills to inspire creation knowledge, sharing and distribution thereof. Contemporary organizations need active and responsible individuals who are capable to make decisions swiftly and responsibly. Leadership influences innovative results and education play a dynamic role in preparing graduates. Critical reflection of extant literature indicates a need for a culture of leadership and innovation to promote organizational sustainability in the globalised world. This study debates the need for HEIs to prepare the graduate for both organizations and society as a whole. This active collaboration should be the very essence of both universities and the industry in order for these to achieve responsible sustainability. Learning and innovation further depend on leadership efficacy. This study follows the pragmatic paradigm methodology. Primary data collection is currently being gathered via the web-based questionnaire link which was made available on the UKZN notice system. The questionnaire has 35 items with a Likert scale of five response options. The purposeful sample method was used, and the population entails the undergraduate and postgraduate students in the College of Law and Business, University of KwaZulu-Natal, South Africa. Limitations include the design of the study and the reliance on the quantitative data as the only method of primary data collection. This study is of added value for scholars and organizations in the innovation economy.Keywords: knowledge creation, learning, performance, sustainability
Procedia PDF Downloads 2871818 Four-Way Coupled CFD-Dem Simulation of Concrete Pipe Flow Using a Non-Newtonian Rheological Model: Investigating the Simulation of Lubrication Layer Formation and Plug Flow Zones
Authors: Tooran Tavangar, Masoud Hosseinpoor, Jeffrey S. Marshall, Ammar Yahia, Kamal Henri Khayat
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In this study, a four-way coupled CFD-DEM methodology was used to simulate the behavior of concrete pipe flow. Fresh concrete, characterized as a biphasic suspension, features aggregates comprising the solid-suspended phase with diverse particle-size distributions (PSD) within a non-Newtonian cement paste/mortar matrix forming the liquid phase. The fluid phase was simulated using CFD, while the aggregates were modeled using DEM. Interaction forces between the fluid and solid particles were considered through CFD-DEM computations. To capture the viscoelastic characteristics of the suspending fluid, a bi-viscous approach was adopted, incorporating a critical shear rate proportional to the yield stress of the mortar. In total, three diphasic suspensions were simulated, each featuring distinct particle size distributions and a concentration of 10% for five subclasses of spherical particles ranging from 1 to 17 mm in a suspending fluid. The adopted bi-viscous approach successfully simulated both un-sheared (plug flow) and sheared zones. Furthermore, shear-induced particle migration (SIPM) was assessed by examining coefficients of variation in particle concentration across the pipe. These SIPM values were then compared with results obtained using CFD-DEM under the Newtonian assumption. The study highlighted the crucial role of yield stress in the mortar phase, revealing that lower yield stress values can lead to increased flow rates and higher SIPM across the pipe.Keywords: computational fluid dynamics, concrete pumping, coupled CFD-DEM, discrete element method, plug flow, shear-induced particle migration.
Procedia PDF Downloads 681817 3D Biomechanical Analysis in Shot Put Techniques of International Throwers
Authors: Satpal Yadav, Ashish Phulkar, Krishna K. Sahu
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Aim: The research aims at doing a 3 Dimension biomechanical analysis in the shot put techniques of International throwers to evaluate the performance. Research Method: The researcher adopted the descriptive method and the data was subjected to calculate by using Pearson’s product moment correlation for the correlation of the biomechanical parameters with the performance of shot put throw. In all the analyses, the 5% critical level (p ≤ 0.05) was considered to indicate statistical significance. Research Sample: Eight (N=08) international shot putters using rotational/glide technique in male category was selected as subjects for the study. The researcher used the following methods and tools to obtain reliable measurements the instrument which was used for the purpose of present study namely the tesscorn slow-motion camera, specialized motion analyzer software, 7.260 kg Shot Put (for a male shot-putter) and steel tape. All measurement pertaining to the biomechanical variables was taken by the principal investigator so that data collected for the present study was considered reliable. Results: The finding of the study showed that negative significant relationship between the angular velocity right shoulder, acceleration distance at pre flight (-0.70), (-0.72) respectively were obtained, the angular displacement of knee, angular velocity right shoulder and acceleration distance at flight (0.81), (0.75) and (0.71) respectively were obtained, the angular velocity right shoulder and acceleration distance at transition phase (0.77), (0.79) respectively were obtained and angular displacement of knee, angular velocity right shoulder, release velocity shot, angle of release, height of release, projected distance and measured distance as the values (0.76), (0.77), (-0.83), (-0.79), (-0.77), (0.99) and (1.00) were found higher than the tabulated value at 0.05 level of significance. On the other hand, there exists an insignificant relationship between the performance of shot put and acceleration distance [m], angular displacement shot, C.G at release and horizontal release distance on the technique of shot put.Keywords: biomechanics, analysis, shot put, international throwers
Procedia PDF Downloads 1871816 Signed Language Phonological Awareness: Building Deaf Children's Vocabulary in Signed and Written Language
Authors: Lynn Mcquarrie, Charlotte Enns
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The goal of this project was to develop a visually-based, signed language phonological awareness training program and to pilot the intervention with signing deaf children (ages 6 -10 years/ grades 1 - 4) who were beginning readers to assess the effects of systematic explicit American Sign Language (ASL) phonological instruction on both ASL vocabulary and English print vocabulary learning. Growing evidence that signing learners utilize visually-based signed language phonological knowledge (homologous to the sound-based phonological level of spoken language processing) when reading underscore the critical need for further research on the innovation of reading instructional practices for visual language learners. Multiple single-case studies using a multiple probe design across content (i.e., sign and print targets incorporating specific ASL phonological parameters – handshapes) was implemented to examine if a functional relationship existed between instruction and acquisition of these skills. The results indicated that for all cases, representing a variety of language abilities, the visually-based phonological teaching approach was exceptionally powerful in helping children to build their sign and print vocabularies. Although intervention/teaching studies have been essential in testing hypotheses about spoken language phonological processes supporting non-deaf children’s reading development, there are no parallel intervention/teaching studies exploring hypotheses about signed language phonological processes in supporting deaf children’s reading development. This study begins to provide the needed evidence to pursue innovative teaching strategies that incorporate the strengths of visual learners.Keywords: American sign language phonological awareness, dual language strategies, vocabulary learning, word reading
Procedia PDF Downloads 3331815 The Status of the Actio Popularis under International Environmental Law in Cases of Damage to Global Commons
Authors: Aimite Jorge, Leenekela Usebiu
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In recent years the International Community has seen a rise of what can be termed as ‘actio popularis”;that is to say lawsuits brought by third parties in the interest of the public or the world community as a whole, such as in cases of genocide and terrorism prosecutions under international law. It is equally clear that under current globalized world the effect of multinational activities on the environment is often felt beyond the borders of the territories where they operate. Equally true is the fact that the correspondence of citizens self-determination with national government is increasingly upset by the increasing willingness of states to share some ‘sovereign powers’ in order to address new economic, environmental and security interdependencies. The ‘unbundling’ of functional governance from fixed territories sees continuously citizens give up their formal approval of key decisions in exchange for a more remote, indirect say in supra-national or international decision-making bodies. The efforts to address a growing transnational flow of ecological harm are at the forefront of such indirect transformations, as evidenced by a proliferation of multilateral environmental agreements (MEAs) over the past three decades. However, unlike the defence of the global commons in cases of terrorism and genocide, there is still to be a clear application of action popularis in the case of environment, despite acknowledgement that the effect of the activities of several multinationals on the environment is as destructive to the global commons as genocide or terrorism are. Thus, this paper looking at specific cases of harmful degradation of the environment by certain multinationals transcending national boundaries, argues that it is high-time for a serious consideration of the application of the actio-popularis to environmental concerns. Although it is acknowledged that in international environmental law the challenge to reach a “critical mass” of recognition and support for an ‘actio-popularis’ for environment damage is particularly demanding, it is worth the try.Keywords: actio popularis in environment law, global commons, transnational environmental damage, law and environment
Procedia PDF Downloads 5691814 A Critical Reflection of Ableist Methodologies: Approaching Interviews and Go-Along Interviews
Authors: Hana Porkertová, Pavel Doboš
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Based on a research project studying the experience of visually disabled people with urban space in the Czech Republic, the conference contribution discusses the limits of social-science methodologies used in sociology and human geography. It draws on actor-network theory, assuming that science does not describe reality but produces it. Methodology connects theory, research questions, ways to answer them (methods), and results. A research design utilizing ableist methodologies can produce ableist realities. Therefore, it was necessary to adjust the methods so that they could mediate blind experience to the scientific community without reproducing ableism. The researchers faced multiple challenges, ranging from questionable validity to how to research experience that differs from that of the researchers who are able-bodied. Finding a suitable theory that could be used as an analytical tool that would demonstrate space and blind experience as multiple, dynamic, and mutually constructed was the first step that could offer a range of potentially productive methods and research questions, as well as bring critically reflected results. Poststructural theory, mainly Deleuze-Guattarian philosophy, was chosen, and two methods were used: interviews and go-along interviews that had to be adjusted to be able to explore blind experience. In spite of a thorough preparation of these methods, new difficulties kept emerging, which exposed the ableist character of scientific knowledge. From the beginning of data collecting, there was an agreement to work in teams with slightly different roles of each of the researchers, which was significant especially during go-along interviews. In some cases, the anticipations of the researchers and participants differed, which led to unexpected and potentially dangerous situations. These were not caused only by the differences between scientific and lay communities but also between able-bodied and disabled people. Researchers were sometimes assigned to the assistants’ roles, and this new position – doing research together – required further negotiations, which also opened various ethical questions.Keywords: ableist methodology, blind experience, go-along interviews, research ethics, scientific knowledge
Procedia PDF Downloads 1651813 Comparative Evaluation of the Effectiveness of Different Mindfulness-Based Interventions on Medically Unexplained Symptoms: A Systematic Review
Authors: R. R. Billones, N. Lukkahatai, L. N. Saligan
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Mindfulness based interventions (MBIs) have been used in medically unexplained symptoms (MUS). This systematic review describes the literature investigating the general effect of MBIs on MUS and identifies the effects of specific MBIs on specific MUS conditions. The preferred reporting items for systematic reviews and meta-analysis guidelines (PRISMA) and the modified Oxford quality scoring system (JADAD) were applied to the review, yielding an initial 1,556 articles. The search engines included PubMed, ScienceDirect, Web of Science, Scopus, EMBASE, and PsychINFO using the search terms: mindfulness, or mediations, or mindful or MBCT or MBSR and medically unexplained symptoms or MUS or fibromyalgia or FMS. A total of 24 articles were included in the final systematic review. MBIs showed large effects on socialization skills for chronic fatigue syndrome (d=0.65), anger in fibromyalgia (d=0.61), improvement of somatic symptoms (d=1.6) and sleep (d=1.12) for painful conditions, physical health for chronic back pain (d=0.51), and disease intensity for irritable bowel disease/syndrome (d=1.13). A manualized MBI that applies the four fundamental elements present in all types of interventions were critical to efficacy. These elements were psycho-education sessions specific to better understand the medical symptoms, the practice of awareness, the non-judgmental observance of the experience at the moment, and the compassion to ones’ self. The effectiveness of different mindfulness interventions necessitates giving attention to improve the gaps that were identified related to home-based practice monitoring, competency training of mindfulness teachers, and sound psychometric properties to measure the mindfulness practice.Keywords: mindfulness-based interventions, medically unexplained symptoms, mindfulness-based cognitive therapy, mindfulness-based stress reduction, fibromyalgia, irritable bowel syndrome
Procedia PDF Downloads 1421812 Glycyrrhizic Acid Inhibits Lipopolysaccharide-Stimulated Bovine Fibroblast-Like Synoviocyte, Invasion through Suppression of TLR4/NF-κB-Mediated Matrix Metalloproteinase-9 Expression
Authors: Hosein Maghsoudi
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Rheumatois arthritis (RA) is progressive inflammatory autoimmune diseases that primarily affect the joints, characterized by synovial hyperplasia and inflammatory cell infiltration, deformed and painful joints, which can lead tissue destruction, functional disability systemic complications, and early dead and socioeconomic costs. The cause of rheumatoid arthritis is unknown, but genetic and environmental factors are contributory and the prognosis is guarded. However, advances in understanding the pathogenesis of the disease have fostered the development of new therapeutics, with improved outcomes. The current treatment strategy, which reflects this progress, is to initiate aggressive therapy soon after diagnosis and to escalate the therapy, guided by an assessment of disease activity, in pursuit of clinical remission. The pathobiology of RA is multifaceted and involves T cells, B cells, fibroblast-like synoviocyte (FLSc) and the complex interaction of many pro-inflammatory cytokine. Novel biologic agents that target tumor necrosis or interlukin (IL)-1 and Il-6, in addition T- and B-cells inhibitors, have resulted in favorable clinical outcomes in patients with RA. Despite this, at least 30% of RA patients are résistance to available therapies, suggesting novel mediators should be identified that can target other disease-specific pathway or cell lineage. Among the inflammatory cell population that might participated in RA pathogenesis, FLSc are crucial in initiaing and driving RA in concert of cartilage and bone by secreting metalloproteinase (MMPs) into the synovial fluid and by direct invasion into extracellular matrix (ECM), further exacerbating joint damage. Invasion of fibroblast-like synoviocytes (FLSc) is critical in the pathogenesis of rheumatoid-arthritis. The metalloproteinase (MMPs) and activator of Toll-like receptor 4 (TLR4)/nuclear factor- κB pthway play a critical role in RA-FLS invasion induced by lipopolysaccharide (LPS). The present study aimed to explore the anti-invasion activity of Glycyrrhizic Acid as a pharmacologically safe phytochemical agent with potent anti-inflammatory properties on IL-1beta and TNF-alpha signalling pathways in Bovine fibroblast-like synoviocyte ex- vitro, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Results showed that Glycyrrhizic Acid suppressed LPS-stimulated bovine FLS migration and invasion by inhibition MMP-9 expression and activity. In addition our results revealed that Glycyrrhizic Acid inhibited the transcriptional activity of MMP-9 by suppression the nbinding activity of NF- κB in the MMP-9 promoter pathway. The extract of licorice (Glycyrrhiza glabra L.) has been widely used for many centuries in the traditional Chinese medicine as native anti-allergic agent. Glycyrrhizin (GL), a triterpenoidsaponin, extracted from the roots of licorice is the most effective compound for inflammation and allergic diseases in human body. The biological and pharmacological studies revealed that GL possesses many pharmacological effects, such as anti-inflammatory, anti-viral and liver protective effects, and the biological effects, such as induction of cytokines (interferon-γ and IL-12), chemokines as well as extrathymic T and anti-type 2 T cells. GL is known in the traditional Chinese medicine for its anti-inflammatory effect, which is originally described by Finney in 1959. The mechanism of the GL-induced anti-inflammatory effect is based on different pathways of the GL-induced selective inhibition of the prostaglandin E2 production, the CK-II- mediated activation of both GL-binding lipoxygenas (gbLOX; 17) and PLA2, an anti-thrombin action of GL and production of the reactive oxygen species (ROS; GL exerts liver protection properties by inhibiting PLA2 or by the hydroxyl radical trapping action, leading to the lowering of serum alanine and aspartate transaminase levels. The present study was undertaken to examine the possible mechanism of anti-inflammatory properties GL on IL-1beta and TNF-alpha signalling pathways in bovine fibroblast-like synoviocyte ex-vivo, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Our results clearly showed that treatment of bovine fibroblast-like synoviocyte with GL suppressed LPS-induced cell migration and invasion. Furthermore, it revealed that GL inhibited the transcription activity of MMP-9 by suppressing the binding activity of NF-κB in the MM-9 promoter. MMP-9 is an important ECM-degrading enzyme and overexpression of MMPs in important of RA-FLSs. LPS can stimulate bovine FLS to secret MMPs, and this induction is regulated at the transcription and translational levels. In this study, LPS treatment of bovine FLS caused an increase in MMP-2 and MMP-9 levels. The increase in MMP-9 expression and secretion was inhibited by ex- vitro. Furthermore, these effects were mimicked by MMP-9 siRNA. These result therefore indicate the the inhibition of LPS-induced bovine FLS invasion by GL occurs primarily by inhibiting MMP-9 expression and activity. Next we analyzed the functional significance of NF-κB transcription of MMP-9 activation in Bovine FLSs. Results from EMSA showed that GL suppressed LPS-induced NF-κB binding to the MMP-9 promotor, as NF-κB regulates transcriptional activation of multiple inflammatory cytokines, we predicted that GL might target NF-κB to suppress MMP-9 transcription by LPS. Myeloid differentiation-factor 88 (MyD88) and TIR-domain containing adaptor protein (TIRAP) are critical proteins in the LPS-induced NF-κB and apoptotic signaling pathways, GL inhibited the expression of TLR4 and MYD88. These results demonstrated that GL suppress LPS-induced MMP-9 expression through the inhibition of the induced TLR4/NFκB signaling pathway. Taken together, our results provide evidence that GL exerts anti-inflammatory effects by inhibition LPS-induced bovine FLSs migration and invasion, and the mechanisms may involve the suppression of TLR4/NFκB –mediated MMP-9 expression. Although further work is needed to clarify the complicated mechanism of GL-induced anti-invasion of bovine FLSs, GL might be used as a further anti-invasion drug with therapeutic efficacy in the treatment of immune-mediated inflammatory disease such as RA.Keywords: glycyrrhizic acid, bovine fibroblast-like synoviocyte, tlr4/nf-κb, metalloproteinase-9
Procedia PDF Downloads 391