Search results for: annual progression
1464 Development of Positron Emission Tomography (PET) Tracers for the in-Vivo Imaging of α-Synuclein Aggregates in α-Synucleinopathies
Authors: Bright Chukwunwike Uzuegbunam, Wojciech Paslawski, Hans Agren, Christer Halldin, Wolfgang Weber, Markus Luster, Thomas Arzberger, Behrooz Hooshyar Yousefi
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There is a need to develop a PET tracer that will enable to diagnosis and track the progression of Alpha-synucleinopathies (Parkinson’s disease [PD], dementia with Lewy bodies [DLB], multiple system atrophy [MSA]) in living subjects over time. Alpha-synuclein aggregates (a-syn), which are present in all the stages of disease progression, for instance, in PD, are a suitable target for in vivo PET imaging. For this reason, we have developed some promising a-syn tracers based on a disarylbisthiazole (DABTA) scaffold. The precursors are synthesized via a modified Hantzsch thiazole synthesis. The precursors were then radiolabeled via one- or two-step radiofluorination methods. The ligands were initially screened using a combination of molecular dynamics and quantum/molecular mechanics approaches in order to calculate the binding affinity to a-syn (in silico binding experiments). Experimental in vitro binding assays were also performed. The ligands were further screened in other experiments such as log D, in vitro plasma protein binding & plasma stability, biodistribution & brain metabolite analyses in healthy mice. Radiochemical yields were up to 30% - 72% in some cases. Molecular docking revealed possible binding sites in a-syn and also the free energy of binding to those sites (-28.9 - -66.9 kcal/mol), which correlated to the high binding affinity of the DABTAs to a-syn (Ki as low as 0.5 nM) and selectivity (> 100-fold) over Aβ and tau, which usually co-exist with a-synin some pathologies. The log D values range from 2.88 - 2.34, which correlated with free-protein fraction of 0.28% - 0.5%. Biodistribution experiments revealed that the tracers are taken up (5.6 %ID/g - 7.3 %ID/g) in the brain at 5 min (post-injection) p.i., and cleared out (values as low as 0.39 %ID/g were obtained at 120 min p.i. Analyses of the mice brain 20 min p.i. Revealed almost no radiometabolites in the brain in most cases. It can be concluded that in silico study presents a new venue for the rational development of radioligands with suitable features. The results obtained so far are promising and encourage us to further validate the DABTAs in autoradiography, immunohistochemistry, and in vivo imaging in non-human primates and humans.Keywords: alpha-synuclein aggregates, alpha-synucleinopathies, PET imaging, tracer development
Procedia PDF Downloads 2371463 Retrospective Study on the Prognosis of Patients with New-Onset Atrial Fibrillation to Evaluate the Risk of Developing Occult Cancer in Absence of Concurrent Chronic Inflammatory Disease
Authors: Helen Huang, Francisco Javier Quesada Ocet, Blanca Quesada Oce, Javier Jimenez Bello, Victor Palanca Gil, Alba Cervero Rubio, Ana Paya Chaume, Alejandro Herreros-Pomares, Fernando Vidal-Vanaclocha, Rafael Paya Serrano, Aurelio Quesada Dorador, Monica Soliman
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Background: Cancer favors both the pro-inflammatory state and autonomic dysfunction, two important mechanisms in the genesis of AF. Atrial remodeling might be caused as a result of paraneoplastic conditions or the result of direct expression of neoplasia. Here, we hypothesize that cancer, through inflammatory mediators, may favor the appearance of AF and patients with the first episode of AF could have a higher risk of developing cancer. Method: Data was collected from patients who attended the emergency department of our hospital for the first episode of AF, diagnosed electrocardiographically, between 2010-2015 (n = 712). The minimum follow-up was 2 years, recording the appearance of cancer, total mortality, recurrences of AF and other events. Patients who developed cancer and those who did not during the 2 years after the onset of AF were compared, as well as with the incidence of cancer in Spain in 2012. Results: After 2 years, 35 patients (4.91%) were diagnosed with cancer, with an annual incidence of 2.45%. Hematological neoplasms were the most frequent (34.28%). The cancer group was older (76.68 +/-12.75 years vs 74.16 +/-12.71; p <0.05) and had fewer typical symptoms (palpitations) (33.38% vs 14.28% , p <0.05). The incidence of cancer in Spain during 2012 was 0.46%, much lower than our sample. When comparing the incidence by age, these differences were maintained both in those over 65 years of age and in those under 65 years of age (2.17% vs. 0.28%; 0.28% vs. 0.18% respectively). Discussion: Therefore, a high incidence of cancer in patients with the first episode of AF was observed (the annual incidence of 2.45% after the onset of AF is 6.1 times that of the general population). After the evaluation of patients with AF in their first detected episode, surveillance of the appearance of cancer should be considered in clinical practice.Keywords: cancer, cardiovascular outcomes, atrial fibrillation, inflammation
Procedia PDF Downloads 1491462 Comparative Analysis of Feature Extraction and Classification Techniques
Authors: R. L. Ujjwal, Abhishek Jain
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In the field of computer vision, most facial variations such as identity, expression, emotions and gender have been extensively studied. Automatic age estimation has been rarely explored. With age progression of a human, the features of the face changes. This paper is providing a new comparable study of different type of algorithm to feature extraction [Hybrid features using HAAR cascade & HOG features] & classification [KNN & SVM] training dataset. By using these algorithms we are trying to find out one of the best classification algorithms. Same thing we have done on the feature selection part, we extract the feature by using HAAR cascade and HOG. This work will be done in context of age group classification model.Keywords: computer vision, age group, face detection
Procedia PDF Downloads 3711461 Radon-222 Concentration and Potential Risk to Workers of Al-Jalamid Phosphate Mines, North Province, Saudi Arabia
Authors: El-Said. I. Shabana, Mohammad S. Tayeb, Maher M. T. Qutub, Abdulraheem A. Kinsara
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Usually, phosphate deposits contain 238U and 232Th in addition to their decay products. Due to their different pathways in the environment, the 238U/232Th activity concentration ratio usually found to be greater than unity in phosphate sediments. The presence of these radionuclides creates a potential need to control exposure of workers in the mining and processing activities of the phosphate minerals in accordance with IAEA safety standards. The greatest dose to workers comes from exposure to radon, especially 222Rn from the uranium series, and has to be controlled. In this regard, radon (222Rn) was measured in the atmosphere (indoor and outdoor) of Al-Jalamid phosphate-mines working area using a portable radon-measurement instrument RAD7, in a purpose of radiation protection. Radon was measured in 61 sites inside the open phosphate mines, the phosphate upgrading facility (offices and rooms of the workers, and in some open-air sites) and in the dwellings of the workers residence-village that lies at about 3 km from the mines working area. The obtained results indicated that the average indoor radon concentration was about 48.4 Bq/m3. Inside the upgrading facility, the average outdoor concentrations were 10.8 and 9.7 Bq/m3 in the concentrate piles and crushing areas, respectively. It was 12.3 Bq/m3 in the atmosphere of the open mines. These values are comparable with the global average values. Based on the average values, the annual effective dose due to radon inhalation was calculated and risk estimates have been done. The average annual effective dose to workers due to the radon inhalation was estimated by 1.32 mSv. The potential excess risk of lung cancer mortality that could be attributed to radon, when considering the lifetime exposure, was estimated by 53.0x10-4. The results have been discussed in detail.Keywords: dosimetry, environmental monitoring, phosphate deposits, radiation protection, radon
Procedia PDF Downloads 2771460 Estimation of Exhaust and Non-Exhaust Particulate Matter Emissions’ Share from On-Road Vehicles in Addis Ababa City
Authors: Solomon Neway Jida, Jean-Francois Hetet, Pascal Chesse
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Vehicular emission is the key source of air pollution in the urban environment. This includes both fine particles (PM2.5) and coarse particulate matters (PM10). However, particulate matter emissions from road traffic comprise emissions from exhaust tailpipe and emissions due to wear and tear of the vehicle part such as brake, tire and clutch and re-suspension of dust (non-exhaust emission). This study estimates the share of the two sources of pollutant particle emissions from on-roadside vehicles in the Addis Ababa municipality, Ethiopia. To calculate its share, two methods were applied; the exhaust-tailpipe emissions were calculated using the Europeans emission inventory Tier II method and Tier I for the non-exhaust emissions (like vehicle tire wear, brake, and road surface wear). The results show that of the total traffic-related particulate emissions in the city, 63% emitted from vehicle exhaust and the remaining 37% from non-exhaust sources. The annual roads transport exhaust emission shares around 2394 tons of particles from all vehicle categories. However, from the total yearly non-exhaust particulate matter emissions’ contribution, tire and brake wear shared around 65% and 35% emanated by road-surface wear. Furthermore, vehicle tire and brake wear were responsible for annual 584.8 tons of coarse particles (PM10) and 314.4 tons of fine particle matter (PM2.5) emissions in the city whereas surface wear emissions were responsible for around 313.7 tons of PM10 and 169.9 tons of PM2.5 pollutant emissions in the city. This suggests that non-exhaust sources might be as significant as exhaust sources and have a considerable contribution to the impact on air quality.Keywords: Addis Ababa, automotive emission, emission estimation, particulate matters
Procedia PDF Downloads 1311459 Antioxidant Status in Synovial Fluid from Osteoarthritis Patients: A Pilot Study in Indian Demography
Authors: S. Koppikar, P. Kulkarni, D. Ingale , N. Wagh, S. Deshpande, A. Mahajan, A. Harsulkar
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Crucial role of reactive oxygen species (ROS) in the progression Osteoarthritis (OA) pathogenesis has been endorsed several times though its exact mechanism remains unclear. Oxidative stress is known to instigate classical stress factors such as cytokines, chemokines and ROS, which hampers cartilage remodelling process and ultimately results in worsening the disease. Synovial fluid (SF) is a biological communicator between cartilage and synovium that accumulates redox and biochemical signalling mediators. The present work attempts to measure several oxidative stress markers in the synovial fluid obtained from knee OA patients with varying degree of disease severity. Thirty OA and five Meniscal-tear (MT) patients were graded using Kellgren-Lawrence scale and assessed for Nitric oxide (NO), Nitrate-Nitrite (NN), 2,2-diphenyl-1-picrylhydrazyl (DPPH), Ferric Reducing Antioxidant Potential (FRAP), Catalase (CAT), Superoxide dismutase (SOD) and Malondialdehyde (MDA) levels for comparison. Out of various oxidative markers studied, NO and SOD showed significant difference between moderate and severe OA (p= 0.007 and p= 0.08, respectively), whereas CAT demonstrated significant difference between MT and mild group (p= 0.07). Interestingly, NN revealed statistically positive correlation with OA severity (p= 0.001 and p= 0.003). MDA, a lipid peroxidation by-product was estimated maximum in early OA when compared to MT (p= 0.06). However, FRAP did not show any correlation with OA severity or MT control. NO is an essential bio-regulatory molecule essential for several physiological processes, and inflammatory conditions. However, due to its short life, exact estimation of NO becomes difficult. NO and its measurable stable products are still it is considered as one of the important biomarker of oxidative damage. Levels of NO and nitrite-nitrate in SF of patients with OA indicated its involvement in the disease progression. When SF groups were compared, a significant correlation among moderate, mild and MT groups was established. To summarize, present data illustrated higher levels of NO, SOD, CAT, DPPH and MDA in early OA in comparison with MT, as a control group. NN had emerged as a prognostic bio marker in knee OA patients, which may act as futuristic targets in OA treatment.Keywords: antioxidant, knee osteoarthritis, oxidative stress, synovial fluid
Procedia PDF Downloads 4801458 Digitalized Cargo Coordination to Eliminate Emissions in the Shipping Ecosystem: A System Dynamical Approach
Authors: Henry Schwartz, Bogdan Iancu, Magnus Gustafsson, Johan Lilius
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The shipping sector generates significant amounts of carbon emissions on annual basis. The excess amount of carbon dioxide is harmful for both the environment and the society, and partly for that reason, there is acute interest to decrease the volume of anthropogenic carbon dioxide emissions in shipping. The usage of the existing cargo carrying capacity can be maximized, and the share of time used in actual transportation operations could be increased if the whole transportation and logistics chain was optimized with the aid of information sharing done through a centralized marketplace and an information-sharing platform. The outcome of this change would be decreased carbon dioxide emission volumes produced per each metric ton of cargo transported by a vessel. Cargo coordination is a platform under development that matches the need for waterborne transportation services with the ships that operate at a given moment in time. In this research, the transition towards adopting cargo coordination is modelled with system dynamics. The model encompasses the complex supply-demand relationships of ship operators and cargo owners. The built scenarios predict the pace at which different stakeholders start using the digitalized platform and by doing so reduce the amount of annual CO2 emissions generated. To improve the reliability of the results, various sensitivity analyses considering the pace of transition as well as the overall impact on the environment (carbon dioxide emissions per amount of cargo transported) are conducted. The results of the study can be used to support investors and politicians in decision making towards more environmentally sustainable solutions. In addition, the model provides concepts and ideas for a wider discussion considering the paths towards carbon neutral transportation.Keywords: carbon dioxide emissions, energy efficiency, sustainable transportation, system dynamics
Procedia PDF Downloads 1491457 Evaluation of NASA POWER and CRU Precipitation and Temperature Datasets over a Desert-prone Yobe River Basin: An Investigation of the Impact of Drought in the North-East Arid Zone of Nigeria
Authors: Yusuf Dawa Sidi, Abdulrahman Bulama Bizi
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The most dependable and precise source of climate data is often gauge observation. However, long-term records of gauge observations, on the other hand, are unavailable in many regions around the world. In recent years, a number of gridded climate datasets with high spatial and temporal resolutions have emerged as viable alternatives to gauge-based measurements. However, it is crucial to thoroughly evaluate their performance prior to utilising them in hydroclimatic applications. Therefore, this study aims to assess the effectiveness of NASA Prediction of Worldwide Energy Resources (NASA POWER) and Climate Research Unit (CRU) datasets in accurately estimating precipitation and temperature patterns within the dry region of Nigeria from 1990 to 2020. The study employs widely used statistical metrics and the Standardised Precipitation Index (SPI) to effectively capture the monthly variability of precipitation and temperature and inter-annual anomalies in rainfall. The findings suggest that CRU exhibited superior performance compared to NASA POWER in terms of monthly precipitation and minimum and maximum temperatures, demonstrating a high correlation and much lower error values for both RMSE and MAE. Nevertheless, NASA POWER has exhibited a moderate agreement with gauge observations in accurately replicating monthly precipitation. The analysis of the SPI reveals that the CRU product exhibits superior performance compared to NASA POWER in accurately reflecting inter-annual variations in rainfall anomalies. The findings of this study indicate that the CRU gridded product is often regarded as the most favourable gridded precipitation product.Keywords: CRU, climate change, precipitation, SPI, temperature
Procedia PDF Downloads 951456 Progression of Trauma: Myth Mess Mastery, Addressing and Grooming
Authors: Stuart Bassman
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Services that focus on the synthesis of research and clinical practice are vital in providing efficacious change for the men and women who have been victims of childhood sexual abuse. This study will address what processes have been helpful in being a catalyst in changing one’s inner life as well as providing meaningful applications and fulfilling experiences. Initially, we would focus on the Myths regarding childhood sexual abuse. This would include Grooming behaviors and Delayed Disclosures. Subsequently, we would address the Mess that follows from not recognizing the adverse impairments that result from Childhood Sexual Abuse. Finally, we would conclude by looking at the Mastery that could arise from moving from being a Victim to a Survivor and a Thriver.Keywords: trauma, childhood, somatic, treatment
Procedia PDF Downloads 581455 Balance Control Mechanisms in Individuals With Multiple Sclerosis in Virtual Reality Environment
Authors: Badriah Alayidi, Emad Alyahya
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Background: Most people with Multiple Sclerosis (MS) report worsening balance as the condition progresses. Poor balance control is also well known to be a significant risk factor for both falling and fear of falling. The increased risk of falls with disease progression thus makes balance control an essential target of gait rehabilitation amongst people with MS. Intervention programs have developed various methods to improve balance control, and accumulating evidence suggests that exercise programs may help people with MS improve their balance. Among these methods, virtual reality (VR) is growing in popularity as a balance-training technique owing to its potential benefits, including better compliance and greater user happiness. However, it is not clear if a VR environment will induce different balance control mechanisms in MS as compared to healthy individuals or traditional environments. Therefore, this study aims to examine how individuals with MS control their balance in a VR setting. Methodology: The proposed study takes an empirical approach to estimate and determine the role of balance response in persons with MS using a VR environment. It will use primary data collected through patient observations, physiological and biomechanical evaluation of balance, and data analysis. Results: The preliminary systematic review and meta-analysis indicated that there was variability in terms of the outcome assessing balance response in people with MS. The preliminary results of these assessments have the potential to provide essential indicators of the progression of MS and contribute to the individualization of treatment and evaluation of the interventions’ effectiveness. The literature describes patients who have had the opportunity to experiment in VR settings and then used what they have learned in the real world, suggesting that this VR setting could be more appealing than conditional settings. The findings of the proposed study will be beneficial in estimating and determining the effect of VR on balance control in persons with MS. In previous studies, VR was shown to be an interesting approach to neurological rehabilitation, but more data are needed to support this approach in MS. Conclusions: The proposed study enables an assessment of balance and evaluations of a variety of physiological implications related to neural activity as well as biomechanical implications related to movement analysis.Keywords: multiple sclerosis, virtual reality, postural control, balance
Procedia PDF Downloads 771454 The Effect of Recycling on Price Volatility of Critical Metals in the EU (2010-2019): An Application of Multivariate GARCH Family Models
Authors: Marc Evenst Jn Jacques, Sophie Bernard
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Electrical and electronic applications, as well as rechargeable batteries, are common in any economy. They also contain a number of important and valuable metals. It is critical to investigate the impact of these new materials or volume sources on the metal market dynamics. This paper investigates the impact of responsible recycling within the European region on metal price volatility. As far as we know, no empirical studies have been conducted to assess the role of metal recycling in metal market price volatility. The goal of this paper is to test the claim that metal recycling helps to cushion price volatility. A set of circular economy indicators/variables, namely, 1) annual total trade values of recycled metals, 2) annual volume of scrap traded and 3) circular material use rate, and 4) information about recycling, are used to estimate the volatility of monthly spot prices of regular metals. A combination of the GARCH-MIDAS model for mixed frequency data sampling and a simple GARCH (1,1) model for the same frequency variables was adopted to examine the potential links between each variable and price volatility. We discovered that from 2010 to 2019, except for Nickel, scrap consumption (Millions of tons), Scrap Trade Values, and Recycled Material use rate had no significant impact on the price volatility of standard metals (Aluminum, Lead) and precious metals (Gold and Platinum). Worldwide interest in recycling has no impact on returns or volatility. Specific interest in metal recycling did have a link to the mean return equation for Aluminum, Gold and to the volatility equation for lead and Nickel.Keywords: recycling, circular economy, price volatility, GARCH, mixed data sampling
Procedia PDF Downloads 601453 Whole Body Vibration and Low Back Disorder among Saskatchewan Farmers: A Prospective Cohort Study
Authors: Samuel Kwaku Essien, Catherine Trask, Niels Koehncke, Brenna Bath
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Background: Low back disorder (LBD) is the most common musculoskeletal problem among farmers, with higher prevalence than other occupations. Operators of tractors and other farm machinery such as combines or all-terrain vehicles (ATV) can have considerable cumulative exposure to whole body vibration (WBV). Although there appears to be an association between LBD and WBV, lack of prospective studies makes the relationship between LBD and WBV unclear. Purpose: This study investigates the association between WBV and LBD among Saskatchewan farmers using a prospective cohort study Methods: The Saskatchewan Farm Injury Cohort Study Phase I (2007) and II (2013) data were used. Baseline data were collected via postal questionnaire on accumulated yearly tractor, combine, and ATV use as well as several covariates to support a biopsychosocial model of LBD. Follow-up data on musculoskeletal symptoms were collected for the 6-year with sample size of 1149. Questions on ‘low back trouble’ (ache, pain, discomfort) experienced in the last 12 months answered by farmer participants as ‘yes’ or ‘no’. A GEE-modified Poisson approach was performed using SPSS 22 and SAS 9.4. Results: Twelve-month Prevalence of LBD was 59.8%. In multivariate analysis of the 6-year follow-up, LBD was associated with ATV operation and tractor operation, with a dose-response relationship for annual accumulated tractor operation. Although combine operation ≥ 61 hrs/year was related to LBD in bivariate analysis, this difference did not persist after adjustment for confounder. Age was found to be a confounder in relationship between WBV and LBD and no interactions were found. Conclusion: Longer annual tractor operation and older age are important predictors of LBD symptoms in farmers. Future research involving direct measurement can help identify appropriate prevention strategies.Keywords: agriculture, low back disorder, low back pain, occupational health
Procedia PDF Downloads 3281452 The Effects of Orally Administered Bacillus Coagulans and Inulin on Prevention and Progression of Rheumatoid Arthritis in Rats
Authors: Khadijeh Abhari, Seyed Shahram Shekarforoush, Saeid Hosseinzadeh
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Probiotics have been considered as an approach to treat and prevent a wide range of inflammatory diseases. The spore forming probiotic strain Bacillus coagulans has demonstrated anti-inflammatory and immune-modulating effects in both animals and humans. The prebiotic, inulin, also potentially affects the immune system as a result of the change in the composition or fermentation profile of the gastrointestinal microbiota. An in vivo trial was conducted to evaluate the effects of probiotic B. coagulans, and inulin, either separately or in combination, on down regulate immune responses and progression of rheumatoid arthritis using induced arthritis rat model. Forty-eight male Wistar rats were randomly divided into 6 groups and fed as follow: 1) control: Normal healthy rats fed by standard diet, 2) Disease control (RA): Arthritic induced (RA) rats fed by standard diet, 3) Prebiotic (PRE): RA+ 5% w/w long chain inulin, 4) Probiotic (PRO): RA+ 109 spores/day B. coagulans by orogastric gavage, 5) Synbiotic (SYN): RA+ 5% w/w long chain inulin and 109 spores/day B. coagulans and 6) Treatment control: (INDO): RA+ 3 mg/kg/day indomethacin by orogastric gavage. Feeding with mentioned diets started on day 0 and continued to the end of study. On day 14, rats were injected with complete Freund’s adjuvant (CFA) to induce arthritis. Arthritis activity was evaluated by biochemical parameters and paw thickness. Biochemical assay for Fibrinogen (Fn), Serum Amyloid A (SAA), TNF-α and Alpha-1-acid glycoprotein (α1AGp) was performed on day 21, 28 and 35 (1, 2 and 3 weeks post RA induction). Pretreatment with PRE, PRO and SYN diets significantly inhibit SAA and Fn production in arthritic rats (P < 0.001). A significant decrease in production of pro-inflammatory cytokines, TNF-α, was seen in PRE, PRO and SYN groups (P < 0.001) which was similar to the effect of the anti-inflammatory drug Indomethacin. Further, there were no significant anti-inflammatory effects observed following different treatments using α1AGp as a RA indicator. Pretreatment with all supplied diets significantly inhibited the development of paw swelling induced by CFA (P < 0.001). Conclusion: Results of this study support that oral intake of probiotic B. coagulans and inulin are able to improve biochemical and clinical parameters of induced RA in rat.Keywords: rheumatoid arthritis, bacillus coagulans, inulin, animal model
Procedia PDF Downloads 3581451 Stability Analysis of Green Coffee Export Markets of Ethiopia: Markov-Chain Analysis
Authors: Gabriel Woldu, Maria Sassi
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Coffee performs a pivotal role in Ethiopia's GDP, revenue, employment, domestic demand, and export earnings. Ethiopia's coffee production and exports show high variability in the amount of production and export earnings. Despite being the continent's fifth-largest coffee producer, Ethiopia has not developed its ability to shine as a major exporter in the globe's green coffee exports. Ethiopian coffee exports were not stable and had high volume and earnings fluctuations. The main aim of this study was to analyze the dynamics of the export of coffee variation to different importing nations using a first-order Markov Chain model. 14 years of time-series data has been used to examine the direction and structural change in the export of coffee. A compound annual growth rate (CAGR) was used to determine the annual growth rate in the coffee export quantity, value, and per-unit price over the study period. The major export markets for Ethiopian coffee were Germany, Japan, and the USA, which were more stable, while countries such as France, Italy, Belgium, and Saudi Arabia were less stable and had low retention rates for Ethiopian coffee. The study, therefore, recommends that Ethiopia should again revitalize its market to France, Italy, Belgium, and Saudi Arabia, as these countries are the major coffee-consuming countries in the world to boost its export stake to the global coffee markets in the future. In order to further enhance export stability, the Ethiopian Government and other stakeholders in the coffee sector should have to work on reducing the volatility of coffee output and exports in order to improve production and quality efficiency, so that stabilize markets as well as to make the product attractive and price competitive in the importing countries.Keywords: coffee, CAGR, Markov chain, direction of trade, Ethiopia
Procedia PDF Downloads 1411450 Molecular Alterations Shed Light on Alteration of Methionine Metabolism in Gastric Intestinal Metaplesia; Insight for Treatment Approach
Authors: Nigatu Tadesse, Ying Liu, Juan Li, Hong Ming Liu
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Gastric carcinogenesis is a lengthy process of histopathological transition from normal to atrophic gastritis (AG) to intestinal metaplasia (GIM), dysplasia toward gastric cancer (GC). The stage of GIM identified as precancerous lesions with resistance to H-pylori eradication and recurrence after endoscopic surgical resection therapies. GIM divided in to two morphologically distinct phenotypes such as complete GIM bearing intestinal type morphology whereas the incomplete type has colonic type morphology. The incomplete type GIM considered to be the greatest risk factor for the development of GC. Studies indicated the expression of the caudal type homeobox 2 (CDX2) gene is responsible for the development of complete GIM but its progressive downregulation from incomplete metaplasia toward advanced GC identified as the risk for IM progression and neoplastic transformation. The downregulation of CDX2 gene have promoted cell growth and proliferation in gastric and colon cancers and ascribed in chemo-treatment inefficacies. CDX2 downregulated through promoter region hypermethylation in which the methylation frequency positively correlated with the dietary history of the patients, suggesting the role of diet as methyl carbon donor sources such as methionine. However, the metabolism of exogenous methionine is yet unclear. Targeting exogenous methionine metabolism has become a promising approach to limits tumor cell growth, proliferation and progression and increase treatment outcome. This review article discusses molecular alterations that could shed light on the potential of exogenous methionine metabolisms, such as gut microbiota alteration as sources of methionine to host cells, metabolic pathway signaling via PI3K/AKt/mTORC1-c-MYC to rewire exogenous methionine and signature of increased gene methylation index, cell growth and proliferation in GIM, with insights to new treatment avenue via targeting methionine metabolism, and the need for future integrated studies on molecular alterations and metabolomics to uncover altered methionine metabolism and characterization of CDX2 methylation in gastric intestinal metaplasia for potential therapeutic exploitation.Keywords: altered methionine metabolism, Intestinal metaplesia, CDX2 gene, gastric cancer
Procedia PDF Downloads 911449 Earnings Management and Tone Management: Evidence from the UK
Authors: Salah Kayed Kayed, Jessica Hong Yang
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This study investigates, whether earnings management in the audited financial statements is associated with tone management in the narrative sections of the annual report in the UK. Earnings management and narrative disclosure are communication strategies used from managers to communicate with investors or other users. Because earnings management and narrative disclosure stem from managers, they can exploit this by doing manipulation in their earnings, and simultaneously disclosing qualitative text (narrative information) in their reports as a tone of words, which will affect users’ perception, and hence users will be misinformed. The association between earnings and tone management can be explained by the self-serving, through cognitive reference points, theory. The sample period lasts from 2010 to 2015, and the sample comprises all non-financial firms that consider under FTSE 350 in any year during the sample period. A list of words from previous research is used to measure the tone in the narrative sections of the annual report. Because this study focuses on the managerial strategic choice and the subjective issues that come from management, it uses the abnormal tone to capture the managerial discretion on tone, and a number of different discretionary accruals proxies to measure earnings management, where accruals management is considered as a manipulation tool from managers to change the users' perception. This research is motivated to fulfil the literature gap by examining the association between earnings and tone management. Moreover, if firms that apply earnings management use tone management to mislead investors, it is beneficial for investors, policy makers, standard setters, or other users to know whether there is an association between earnings management and tone management. Clearly, we believe that this study is fundamental in the accounting context, where it evaluates the communication strategies that are used in firms' financial reports. Consistent with prior research, it is expected that tone management is positively associated with earnings management. This means that firms that use earnings management have incentives to manipulate in their narrative disclosure through tone of words, to reflect a good perception for users, which will conceal the earnings management techniques used in their reporting.Keywords: earnings management, FTSE 350, narrative disclosure, tone management
Procedia PDF Downloads 2881448 Morphology Feature of Nanostructure Bainitic Steel after Tempering Treatment
Authors: Chih Yuan Chen, Chien Chon Chen, Jin-Shyong Lin
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The microstructure characterization of tempered nanocrystalline bainitic steel is investigated in the present study. It is found that two types of plastic relaxation, dislocation debris and nanotwin, occurs in the displacive transformation due to relatively low transformation temperature and high carbon content. Because most carbon atoms trap in the dislocation, high dislocation density can be sustained during the tempering process. More carbides only can be found in the high tempered temperature due to intense recovery progression.Keywords: nanostructure bainitic steel, tempered, TEM, nano-twin, dislocation debris, accommodation
Procedia PDF Downloads 5381447 CFD Modeling of Pollutant Dispersion in a Free Surface Flow
Authors: Sonia Ben Hamza, Sabra Habli, Nejla Mahjoub Said, Hervé Bournot, Georges Le Palec
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In this work, we determine the turbulent dynamic structure of pollutant dispersion in two-phase free surface flow. The numerical simulation was performed using ANSYS Fluent. The flow study is three-dimensional, unsteady and isothermal. The study area has been endowed with a rectangular obstacle to analyze its influence on the hydrodynamic variables and progression of the pollutant. The numerical results show that the hydrodynamic model provides prediction of the dispersion of a pollutant in an open channel flow and reproduces the recirculation and trapping the pollutant downstream near the obstacle.Keywords: CFD, free surface, polluant dispersion, turbulent flows
Procedia PDF Downloads 5481446 The Descending Genicular Artery Perforator Free Flap as a Reliable Flap: Literature Review
Authors: Doran C. Kalmin
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The descending genicular artery (DGA) perforator free flap provides an alternative to free flap reconstruction based on a review of the literature detailing both anatomical and clinical studies. The descending genicular artery (DGA) supplies skin, muscle, tendon, and bone located around the medial aspect of the knee that has been used in several pioneering reports in reconstructing defects located in various areas throughout the body. After the success of the medial femoral condyle flap in early studies, a small number of studies have been published detailing the use of the DGA in free flap reconstruction. Despite early success in the use of the DGA flap, acceptance within the Plastic and Reconstructive Surgical community has been limited due primarily to anatomical variations of the pedicle. This literature review is aimed at detailing the progression of the DGA perforator free flap and its variations as an alternative and reliable free flap for reconstruction of composite defects with an exploration into both anatomical and clinical studies. A literature review was undertaken, and the progression of the DGA flap is explored from the early review by Acland et al. pioneering the saphenous free flap to exploring modern changes and studies of the anatomy of the DGA. An extensive review of the literature was undertaken that details the anatomy and its variations, approaches to harvesting the flap, the advantages, and disadvantages of the DGA perforator free flap as well as flap outcomes. There are 15 published clinical series of DGA perforator free flaps that incorporate cutaneous, osteoperiosteal, cartilage, osteocutaneous, osteoperiosteal and muscle, osteoperiosteal and subcutaneous and tendocutatenous. The commonest indication for using a DGA free flap was for non-union of bone, particularly that of the scaphoid whereby the medial femoral condyle could be used. In the case series, a success rate of over 90% was established, showing that these early studies have had good success with a wide range of tissue transfers. The greatest limitation is the anatomical variation of the DGA and therefore, the challenges associated with raising the flap. Despite the variation in anatomy and around 10-15% absence of the DGA, the saphenous artery can be used as well as the superior medial genicular artery if the vascular bone is required as part of the flap. Despite only a handful of anatomical and clinical studies describing the DGA perforator free flap, it ultimately provides a reliable flap that can include a variety of composite structure used for reconstruction in almost any area throughout the body. Although it has limitations, it provides a reliable option for free flap reconstruction that can routinely be performed as a single-stage procedure.Keywords: anatomical study, clinical study, descending genicular artery, literature review, perforator free flap reconstruction
Procedia PDF Downloads 1451445 Uptake of Cervical Cancer Screening Services and Associated Factors at KISWA HCII, Kampala, Uganda
Authors: Mary Kiviiri Nakawuka, Mary Namugalu, Andrew Otiti
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BACKGROUND Cervical cancer is the fourth most common cancer in women and seventh overall among all cancers worldwide. It accounts for about 7.5% of all female-cancer deaths with 85% occurring in low and middle-income countries and the first most common female cancer in women aged 15 to 44 years in Uganda with an annual number of new cases at 3,915 and 2,275 annual number of cervical cancer deaths in 2012 (ICO INFORMATION CENTRE ON HPV AND CANCER, 2017).Despite the available free cervical cancer screening services whose uptake has been documented to improve the chances of successful treatment of pre-cancers and cancers among women of reproductive age, there is a low uptake of these services thus we sought to examine the uptake of cervical cancer services and associated factors among women of reproductive age (25-49) attending the ART clinic of KISWA HCII in Kampala, Uganda METHODS The research was carried out in the ART clinic of KISWA HCII among 385 participants. An analytical, cross-sectional study with quantitative methods of data collection was used. The study adopted a non-probability convenience sampling method to select participants. Quantitative data was collected through structured questionnaires. RESULTS 72.2% of the participants were found to have been screened for cervical cancer. 36 % of the screened women had a positive HPV or VIA result ,59.2% of the screened women had a negative HPV or VIA result and 4.8% had an invalid HPV test result. Only 39.5% of the participants had adequate overall knowledge about cervical cancer, more than a third of the participants (50%) had moderate or low knowledge and minority of them (10.5%) had no knowledge. There was no significant association between the uptake of cervical cancer screening services among participants and their socio-demographic characteristics. CONCLUSIONS Although majority of the women surveyed had been screened for cervical cancer, a comparatively large number of participants had inadequate knowledge about cervical cancer and therefore there is still need to continue teaching about cervical cancer and this may include education campaigns, improvements to the accessibility and convenience of the screening services.Keywords: cervical cancer uptake, cervical cancer screening, women of reproductive age., cervical cancer knowledge
Procedia PDF Downloads 981444 Environmental Accounting Practice: Analyzing the Extent and Qualification of Environmental Disclosures of Turkish Companies Located in BIST-XKURY Index
Authors: Raif Parlakkaya, Mustafa Nihat Demirci, Mehmet Nuri Salur
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Environmental pollution has detrimental effects on the quality of our life and its scope has reached such an extent that measures are being taken both at the national and international levels to reduce, prevent and mitigate its impact on social, economic and political spheres. Therefore, awareness of environmental problems has been increasing among stakeholders and accordingly among companies. It is seen that corporate reporting is expanding beyond environmental performance. Primary purpose of publishing an environmental report is to provide specific audiences with useful, meaningful information. This paper is intended to analyze the extent and qualification of environmental disclosures of Turkish publicly quoted firms and see how it varies from one sector to another. The data for the study were collected from annual activity reports of companies, listed on the corporate governance index (BIST-XKURY) of Istanbul Stock Exchange. Content analysis was the research methodology used to measure the extent of environmental disclosure. Accordingly, 2015 annual activity reports of companies that carry out business in some particular fields were acquired from Capital Market Board, websites of Public Disclosure Platform and companies’ own websites. These reports were categorized into five main aspects: Environmental policies, environmental management systems, environmental protection and conservation activities, environmental awareness and information on environmental lawsuits. Subsequently, each component was divided into several variables related to what each firm is supposed to disclose about environmental information. In this context, the nature and scope of the information disclosed on each item were assessed according to five different ways (N.I: No Information; G.E.: General Explanations; Q.E.: Qualitative Detailed Explanations; N.E.: Quantitative (numerical) Detailed Explanations; Q.&N.E.: Both Qualitative and Quantitative Explanations).Keywords: environmental accounting, disclosure, corporate governance, content analysis
Procedia PDF Downloads 2661443 Spatial Climate Changes in the Province of Macerata, Central Italy, Analyzed by GIS Software
Authors: Matteo Gentilucci, Marco Materazzi, Gilberto Pambianchi
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Climate change is an increasingly central issue in the world, because it affects many of human activities. In this context regional studies are of great importance because they sometimes differ from the general trend. This research focuses on a small area of central Italy which overlooks the Adriatic Sea, the province of Macerata. The aim is to analyze space-based climate changes, for precipitation and temperatures, in the last 3 climatological standard normals (1961-1990; 1971-2000; 1981-2010) through GIS software. The data collected from 30 weather stations for temperature and 61 rain gauges for precipitation were subject to quality controls: validation and homogenization. These data were fundamental for the spatialization of the variables (temperature and precipitation) through geostatistical techniques. To assess the best geostatistical technique for interpolation, the results of cross correlation were used. The co-kriging method with altitude as independent variable produced the best cross validation results for all time periods, among the methods analysed, with 'root mean square error standardized' close to 1, 'mean standardized error' close to 0, 'average standard error' and 'root mean square error' with similar values. The maps resulting from the analysis were compared by subtraction between rasters, producing 3 maps of annual variation and three other maps for each month of the year (1961/1990-1971/2000; 1971/2000-1981/2010; 1961/1990-1981/2010). The results show an increase in average annual temperature of about 0.1°C between 1961-1990 and 1971-2000 and 0.6 °C between 1961-1990 and 1981-2010. Instead annual precipitation shows an opposite trend, with an average difference from 1961-1990 to 1971-2000 of about 35 mm and from 1961-1990 to 1981-2010 of about 60 mm. Furthermore, the differences in the areas have been highlighted with area graphs and summarized in several tables as descriptive analysis. In fact for temperature between 1961-1990 and 1971-2000 the most areally represented frequency is 0.08°C (77.04 Km² on a total of about 2800 km²) with a kurtosis of 3.95 and a skewness of 2.19. Instead, the differences for temperatures from 1961-1990 to 1981-2010 show a most areally represented frequency of 0.83 °C, with -0.45 as kurtosis and 0.92 as skewness (36.9 km²). Therefore it can be said that distribution is more pointed for 1961/1990-1971/2000 and smoother but more intense in the growth for 1961/1990-1981/2010. In contrast, precipitation shows a very similar shape of distribution, although with different intensities, for both variations periods (first period 1961/1990-1971/2000 and second one 1961/1990-1981/2010) with similar values of kurtosis (1st = 1.93; 2nd = 1.34), skewness (1st = 1.81; 2nd = 1.62 for the second) and area of the most represented frequency (1st = 60.72 km²; 2nd = 52.80 km²). In conclusion, this methodology of analysis allows the assessment of small scale climate change for each month of the year and could be further investigated in relation to regional atmospheric dynamics.Keywords: climate change, GIS, interpolation, co-kriging
Procedia PDF Downloads 1321442 Radioactivity Assessment of Sediments in Negombo Lagoon Sri Lanka
Authors: H. M. N. L. Handagiripathira
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The distributions of naturally occurring and anthropogenic radioactive materials were determined in surface sediments taken at 27 different locations along the bank of Negombo Lagoon in Sri Lanka. Hydrographic parameters of lagoon water and the grain size analyses of the sediment samples were also carried out for this study. The conductivity of the adjacent water was varied from 13.6 mS/cm to 55.4 mS/cm near to the southern end and the northern end of the lagoon, respectively, and equally salinity levels varied from 7.2 psu to 32.1 psu. The average pH in the water was 7.6 and average water temperature was 28.7 °C. The grain size analysis emphasized the mass fractions of the samples as sand (60.9%), fine sand (30.6%) and fine silt+clay (1.3%) in the sampling locations. The surface sediment samples of wet weight, 1 kg each from upper 5-10 cm layer, were oven dried at 105 °C for 24 hours to get a constant weight, homogenized and sieved through a 2 mm sieve (IAEA technical series no. 295). The radioactivity concentrations were determined using gamma spectrometry technique. Ultra Low Background Broad Energy High Purity Ge Detector, BEGe (Model BE5030, Canberra) was used for radioactivity measurement with Canberra Industries' Laboratory Source-less Calibration Software (LabSOCS) mathematical efficiency calibration approach and Geometry composer software. The mean activity concentration was found to be 24 ± 4, 67 ± 9, 181 ± 10, 59 ± 8, 3.5 ± 0.4 and 0.47 ± 0.08 Bq/kg for 238U, 232Th, 40K, 210Pb, 235U and 137Cs respectively. The mean absorbed dose rate in air, radium equivalent activity, external hazard index, annual gonadal dose equivalent and annual effective dose equivalent were 60.8 nGy/h, 137.3 Bq/kg, 0.4, 425.3 mSv/year and 74.6 mSv/year, respectively. The results of this study will provide baseline information on the natural and artificial radioactive isotopes and environmental pollution associated with information on radiological risk.Keywords: gamma spectrometry, lagoon, radioactivity, sediments
Procedia PDF Downloads 1421441 Implementing the WHO Air Quality Guideline for PM2.5 Worldwide can Prevent Millions of Premature Deaths Per Year
Authors: Despina Giannadaki, Jos Lelieveld, Andrea Pozzer, John Evans
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Outdoor air pollution by fine particles ranks among the top ten global health risk factors that can lead to premature mortality. Epidemiological cohort studies, mainly conducted in United States and Europe, have shown that the long-term exposure to PM2.5 (particles with an aerodynamic diameter less than 2.5μm) is associated with increased mortality from cardiovascular, respiratory diseases and lung cancer. Fine particulates can cause health impacts even at very low concentrations. Previously, no concentration level has been defined below which health damage can be fully prevented. The World Health Organization ambient air quality guidelines suggest an annual mean PM2.5 concentration limit of 10μg/m3. Populations in large parts of the world, especially in East and Southeast Asia, and in the Middle East, are exposed to high levels of fine particulate pollution that by far exceeds the World Health Organization guidelines. The aim of this work is to evaluate the implementation of recent air quality standards for PM2.5 in the EU, the US and other countries worldwide and estimate what measures will be needed to substantially reduce premature mortality. We investigated premature mortality attributed to fine particulate matter (PM2.5) under adults ≥ 30yrs and children < 5yrs, applying a high-resolution global atmospheric chemistry model combined with epidemiological concentration-response functions. The latter are based on the methodology of the Global Burden of Disease for 2010, assuming a ‘safe’ annual mean PM2.5 threshold of 7.3μg/m3. We estimate the global premature mortality by PM2.5 at 3.15 million/year in 2010. China is the leading country with about 1.33 million, followed by India with 575 thousand and Pakistan with 105 thousand. For the European Union (EU) we estimate 173 thousand and the United States (US) 52 thousand in 2010. Based on sensitivity calculations we tested the gains from PM2.5 control by applying the air quality guidelines (AQG) and standards of the World Health Organization (WHO), the EU, the US and other countries. To estimate potential reductions in mortality rates we take into consideration the deaths that cannot be avoided after the implementation of PM2.5 upper limits, due to the contribution of natural sources to total PM2.5 and therefore to mortality (mainly airborne desert dust). The annual mean EU limit of 25μg/m3 would reduce global premature mortality by 18%, while within the EU the effect is negligible, indicating that the standard is largely met and that stricter limits are needed. The new US standard of 12μg/m3 would reduce premature mortality by 46% worldwide, 4% in the US and 20% in the EU. Implementing the AQG by the WHO of 10μg/m3 would reduce global premature mortality by 54%, 76% in China and 59% in India. In the EU and US, the mortality would be reduced by 36% and 14%, respectively. Hence, following the WHO guideline will prevent 1.7 million premature deaths per year. Sensitivity calculations indicate that even small changes at the lower PM2.5 standards can have major impacts on global mortality rates.Keywords: air quality guidelines, outdoor air pollution, particulate matter, premature mortality
Procedia PDF Downloads 3111440 Recreation and Environmental Quality of Tropical Wetlands: A Social Media Based Spatial Analysis
Authors: Michael Sinclair, Andrea Ghermandi, Sheela A. Moses, Joseph Sabu
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Passively crowdsourced data, such as geotagged photographs from social media, represent an opportunistic source of location-based and time-specific behavioral data for ecosystem services analysis. Such data have innovative applications for environmental management and protection, which are replicable at wide spatial scales and in the context of both developed and developing countries. Here we test one such innovation, based on the analysis of the metadata of online geotagged photographs, to investigate the provision of recreational services by the entire network of wetland ecosystems in the state of Kerala, India. We estimate visitation to individual wetlands state-wide and extend, for the first time to a developing region, the emerging application of cultural ecosystem services modelling using data from social media. The impacts of restoration of wetland areal extension and water quality improvement are explored as a means to inform more sustainable management strategies. Findings show that improving water quality to a level suitable for the preservation of wildlife and fisheries could increase annual visits by 350,000, an increase of 13% in wetland visits state-wide, while restoring previously encroached wetland area could result in a 7% increase in annual visits, corresponding to 49,000 visitors, in the Ashtamudi and Vembanad lakes alone, two large coastal Ramsar wetlands in Kerala. We discuss how passive crowdsourcing of social media data has the potential to improve current ecosystem service analyses and environmental management practices also in the context of developing countries.Keywords: coastal wetlands, cultural ecosystem services, India, passive crowdsourcing, social media, wetland restoration
Procedia PDF Downloads 1581439 Correlation Between the Toxicity Grade of the Adverse Effects in the Course of the Immunotherapy of Lung Cancer and Efficiency of the Treatment in Anti-PD-L1 and Anti-PD-1 Drugs - Own Clinical Experience
Authors: Anna Rudzińska, Katarzyna Szklener, Pola Juchaniuk, Anna Rodzajweska, Katarzyna Machulska-Ciuraj, Monika Rychlik- Grabowska, Michał łOziński, Agnieszka Kolak-Bruks, SłAwomir Mańdziuk
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Introduction: Immune checkpoint inhibition (ICI) belongs to the modern forms of anti-cancer treatment. Due to the constant development and continuous research in the field of ICI, many aspects of the treatment are yet to be discovered. One of the less researched aspects of ICI treatment is the influence of the adverse effects on the treatment success rate. It is suspected that adverse events in the course of the ICI treatment indicate a better response rate and correlate with longer progression-free- survival. Methodology: The research was conducted with the usage of the documentation of the Department of Clinical Oncology and Chemotherapy. Data of the patients with a lung cancer diagnosis who were treated between 2019-2022 and received ICI treatment were analyzed. Results: Out of over 133 patients whose data was analyzed, the vast majority were diagnosed with non-small cell lung cancer. The majority of the patients did not experience adverse effects. Most adverse effects reported were classified as grade 1 or grade 2 according to CTCAE classification. Most adverse effects involved skin, thyroid and liver toxicity. Statistical significance was found for the adverse effect incidence and overall survival (OS) and progression-free survival (PFS) (p=0,0263) and for the time of toxicity onset and OS and PFS (p<0,001). The number of toxicity sites was statistically significant for prolonged PFS (p=0.0315). The highest OS was noted in the group presenting grade 1 and grade 2 adverse effects. Conclusions: Obtained results confirm the existence of the prolonged OS and PFS in the adverse-effects-charged patients, mostly in the group presenting mild to intermediate (Grade 1 and Grade 2) adverse effects and late toxicity onset. Simultaneously our results suggest a correlation between treatment response rate and the toxicity grade of the adverse effects and the time of the toxicity onset. Similar results were obtained in several similar research conducted - with the proven tendency of better survival in mild and moderate toxicity; meanwhile, other studies in the area suggested an advantage in patients with any toxicity regardless of the grade. The contradictory results strongly suggest the need for further research on this topic, with a focus on additional factors influencing the course of the treatment.Keywords: adverse effects, immunotherapy, lung cancer, PD-1/PD-L1 inhibitors
Procedia PDF Downloads 931438 Clinicopathological Characteristics in Male Breast Cancer: A Case Series and Literature Review
Authors: Mohamed Shafi Mahboob Ali
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Male breast cancer (MBC) is a rare entity with overall cases reported less than 1%. However, the incidence of MBC is regularly rising every year. Due to the lack of data on MBC, diagnosis and treatment are tailored to female breast cancer. MBC risk increases with age and is usually diagnosed ten years late as the disease progression is slow compared to female breast cancer (FBC). The most common feature of MBC is an intra-ductal variant, and often, upon diagnosis, the stage of the disease is already advanced. The Prognosis of MBC is often flawed, but new treatment modalities are emerging with the current knowledge and advancement. We presented a series of male breast cancer in our center, highlighting the clinicopathological, radiological and treatment options.Keywords: male, breast, cancer, clinicopathology, ultrasound, CT scan
Procedia PDF Downloads 1021437 A Computational Investigation of Potential Drugs for Cholesterol Regulation to Treat Alzheimer’s Disease
Authors: Marina Passero, Tianhua Zhai, Zuyi (Jacky) Huang
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Alzheimer’s disease has become a major public health issue, as indicated by the increasing populations of Americans living with Alzheimer’s disease. After decades of extensive research in Alzheimer’s disease, only seven drugs have been approved by Food and Drug Administration (FDA) to treat Alzheimer’s disease. Five of these drugs were designed to treat the dementia symptoms, and only two drugs (i.e., Aducanumab and Lecanemab) target the progression of Alzheimer’s disease, especially the accumulation of amyloid-b plaques. However, controversial comments were raised for the accelerated approvals of either Aducanumab or Lecanemab, especially with concerns on safety and side effects of these two drugs. There is still an urgent need for further drug discovery to target the biological processes involved in the progression of Alzheimer’s disease. Excessive cholesterol has been found to accumulate in the brain of those with Alzheimer’s disease. Cholesterol can be synthesized in both the blood and the brain, but the majority of biosynthesis in the adult brain takes place in astrocytes and is then transported to the neurons via ApoE. The blood brain barrier separates cholesterol metabolism in the brain from the rest of the body. Various proteins contribute to the metabolism of cholesterol in the brain, which offer potential targets for Alzheimer’s treatment. In the astrocytes, SREBP cleavage-activating protein (SCAP) binds to Sterol Regulatory Element-binding Protein 2 (SREBP2) in order to transport the complex from the endoplasmic reticulum to the Golgi apparatus. Cholesterol is secreted out of the astrocytes by ATP-Binding Cassette A1 (ABCA1) transporter. Lipoprotein receptors such as triggering receptor expressed on myeloid cells 2 (TREM2) internalize cholesterol into the microglia, while lipoprotein receptors such as Low-density lipoprotein receptor-related protein 1 (LRP1) internalize cholesterol into the neuron. Cytochrome P450 Family 46 Subfamily A Member 1 (CYP46A1) converts excess cholesterol to 24S-hydroxycholesterol (24S-OHC). Cholesterol has been approved for its direct effect on the production of amyloid-beta and tau proteins. The addition of cholesterol to the brain promotes the activity of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), secretase, and amyloid precursor protein (APP), which all aid in amyloid-beta production. The reduction of cholesterol esters in the brain have been found to reduce phosphorylated tau levels in mice. In this work, a computational pipeline was developed to identify the protein targets involved in cholesterol regulation in brain and further to identify chemical compounds as the inhibitors of a selected protein target. Since extensive evidence shows the strong correlation between brain cholesterol regulation and Alzheimer’s disease, a detailed literature review on genes or pathways related to the brain cholesterol synthesis and regulation was first conducted in this work. An interaction network was then built for those genes so that the top gene targets were identified. The involvement of these genes in Alzheimer’s disease progression was discussed, which was followed by the investigation of existing clinical trials for those targets. A ligand-protein docking program was finally developed to screen 1.5 million chemical compounds for the selected protein target. A machine learning program was developed to evaluate and predict the binding interaction between chemical compounds and the protein target. The results from this work pave the way for further drug discovery to regulate brain cholesterol to combat Alzheimer’s disease.Keywords: Alzheimer’s disease, drug discovery, ligand-protein docking, gene-network analysis, cholesterol regulation
Procedia PDF Downloads 771436 Estimation of Radon (²²²Rn) Activity Concentration Levels and Associated Effective Dose in Bottled Drinking Water from South Africa
Authors: Samuel Odumu Ogana John, Stephen Friday Olukotun, Manny Mathuthu
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Radon-222 (²²²Rn), a naturally occurring radioactive gas, poses potential health risks due to its inhalation and ingestion, especially through drinking water. This study investigates the activity concentration levels of ²²²Rn in 21 brands of bottled water samples collected from the open market in South Africa. The samples were analyzed using a highly sensitive system consisting of the Ionization Chamber AlphaGUARD (PQ 2000), an AquaKIT set, and an AlphaPUMP, ensuring precise measurement of radon activity. The results revealed significant variations in radon concentrations across different brands, with values ranging from 0.062 ± 0.046 Bq/m³ to 0.198 ± 0.286 Bq/mv³, with a mean of 0.118 ± 0.034 Bq/m³. These measurements were then used to estimate the annual effective ingestion dose of radiation for consumers across various age groups based on the guidelines provided by the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR). The mean effective doses were found to be 4.057 × 10⁻⁴ ± 1.188 × 10⁻⁴ mSv/y for infants (1–2 years), 2.428 × 10⁻⁴ ± 7.111 × 10⁻⁵ mSv/y for children (7–12 years), and 2.058 × 10⁻⁴ ± 6.026 × 10⁻⁵ mSv/y for adults, all of which are below the recommended international safety limits and are comparable to other published studies. These findings suggest that bottled drinking water in South Africa is safe for consumption and does not pose a significant health hazard from ²²²Rn radiation. The study underscores the importance of monitoring radon levels in bottled water to assess the associated radiological health risks, particularly in South Africa, where access to safe drinking water is essential. This research provides baseline data for future regulatory frameworks and policy development and can serve as a valuable reference for bottled water producers. Furthermore, it highlights the need for continued investigation into the regulation and mitigation of radon exposure in drinking water sources throughout the country.Keywords: Radon-222, activity concentration levels, annual effective ingestion dose, bottled drinking water, South Africa
Procedia PDF Downloads 81435 Assessing the Macroeconomic Effects of Fiscal Policy Changes in Egypt: A Bayesian Structural Vector Autoregression Approach
Authors: Walaa Diab, Baher Atlam, Nadia El Nimer
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Egypt faces many obvious economic challenges, and it is so clear that a real economic transformation is needed to address those problems, especially after the recent decisions of floating the Egyptian pound and the gradual subsidy cuts that are trying to meet the needed conditions to get the IMF support of (a £12bn loan) for its economic reform program. Following the post-2008 revival of the interest in the fiscal policy and its vital role in speeding up or slowing down the economic growth. Here comes the value of this paper as it seeks to analyze the macroeconomic effects of fiscal policy in Egypt by applying A Bayesian SVAR Approach. The study uses the Bayesian method because it includes the prior information and no relevant information is omitted and so it is well suited for rational, evidence-based decision-making. Since the study aims to define the effects of fiscal policy shocks in Egypt to help the decision-makers in determining the proper means to correct the structural problems in the Egyptian economy, it has to study the period of 1990s economic reform, but unfortunately; the available data is on an annual frequency. Thus, it uses annual time series to study the period 1991: 2005 And quarterly data over the period 2006–2016. It uses a set of six main variables includes government expenditure and net tax revenues as fiscal policy arms affecting real GDP, unemployment, inflation and the interest rate. The study also tries to assess the 'crowding out' effects by considering the effects of government spending and government revenue shocks on the composition of GDP, namely, on private consumption and private investment. Last but not least the study provides its policy implications regarding the needed role of fiscal policy in Egypt in the upcoming economic reform building on the results it concludes from the previous reform program.Keywords: fiscal policy, government spending, structural vector autoregression, taxation
Procedia PDF Downloads 281