Search results for: active control
1250 The Second Generation of Tyrosine Kinase Inhibitor Afatinib Controls Inflammation by Regulating NLRP3 Inflammasome Activation
Authors: Shujun Xie, Shirong Zhang, Shenglin Ma
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Background: Chronic inflammation might lead to many malignancies, and inadequate resolution could play a crucial role in tumor invasion, progression, and metastases. A randomised, double-blind, placebo-controlled trial shows that IL-1β inhibition with canakinumab could reduce incident lung cancer and lung cancer mortality in patients with atherosclerosis. The process and secretion of proinflammatory cytokine IL-1β are controlled by the inflammasome. Here we showed the correlation of the innate immune system and afatinib, a tyrosine kinase inhibitor targeting epidermal growth factor receptor (EGFR) in non-small cell lung cancer. Methods: Murine Bone marrow derived macrophages (BMDMs), peritoneal macrophages (PMs) and THP-1 were used to check the effect of afatinib on the activation of NLRP3 inflammasome. The assembly of NLRP3 inflammasome was check by co-immunoprecipitation of NLRP3 and apoptosis-associated speck-like protein containing CARD (ASC), disuccinimidyl suberate (DSS)-cross link of ASC. Lipopolysaccharide (LPS)-induced sepsis and Alum-induced peritonitis were conducted to confirm that afatinib could inhibit the activation of NLRP3 in vivo. Peripheral blood mononuclear cells (PBMCs) from non-small cell lung cancer (NSCLC) patients before or after taking afatinib were used to check that afatinib inhibits inflammation in NSCLC therapy. Results: Our data showed that afatinib could inhibit the secretion of IL-1β in a dose-dependent manner in macrophage. Moreover, afatinib could inhibit the maturation of IL-1β and caspase-1 without affecting the precursors of IL-1β and caspase-1. Next, we found that afatinib could block the assembly of NLRP3 inflammasome and the ASC speck by blocking the interaction of the sensor protein NLRP3 and the adaptor protein ASC. We also found that afatinib was able to alleviate the LPS-induced sepsis in vivo. Conclusion: Our study found that afatinib could inhibit the activation of NLRP3 inflammasome in macrophage, providing new evidence that afatinib could target the innate immune system to control chronic inflammation. These investigations will provide significant experimental evidence in afatinib as therapeutic drug for non-small cell lung cancer or other tumors and NLRP3-related diseases and will explore new targets for afatinib.Keywords: inflammasome, afatinib, inflammation, tyrosine kinase inhibitor
Procedia PDF Downloads 1201249 Circadian Rhythmic Expression of Choroid Plexus Membrane Transport Proteins
Authors: Rafael Mineiro, André Furtado, Isabel Gonçalves, Cecília Santos, Telma Quintela
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The choroid plexus (CP) epithelial cells form the blood-cerebrospinal fluid barrier. This barrier is highly important for brain protection by physically separating the blood from the cerebrospinal fluid, controlling the trafficking of molecules, including therapeutic drugs, from blood to the brain. The control is achieved by tight junctions between epithelial cells, membrane receptors and transport proteins from the solute carrier and ATP-binding cassette superfamily on the choroid plexus epithelial cells membrane. Previous research of our group showed a functional molecular clock in the CP. The key findings included a rhythmic expression of Bmal1, Per2, and Cry2 in female rat CP. and a rhythmic expression of Cry2 and Per2 in male rat CP. Furthermore, in cultured rat CP epithelial cells we already showed that 17β-estradiol upregulates the expression of Bmal1 and Per1, where the Per1 and Per2 upregulation was abrogated in the presence of the estrogen receptors antagonist ICI. These findings, together with the fact that the CP produces robust rhythms, prompt us to understand the impact of sex hormones and circadian rhythms in CP drug transporters expression, which is a step towards the development and optimization of therapeutic strategies for efficiently delivering drugs to the brain. For that, we analyzed the circadian rhythmicity of the Abcb1, Abcc2, Abcc4 Abcg2, and Oat3 drug transporters at the CP of male and female rats. This analysis was performed by accessing the gene expression of the mentioned transporters at 4 time points by RT-qPCR and the presence of rhythms was evaluated by the CircWave software. Our findings showed a rhythmic expression of Abcc1 in the CP of male rats, of Abcg2 in female rats, and of Abcc4 and Oat3 in both male and female rats with an almost antiphasic pattern between male and female rats for Abcc4. In conclusion, these findings translated to a functional point of view may account for daily variations in brain permeability for several therapeutic drugs, making our findings important data for the future establishment and development of therapeutic strategies according to daytime.Keywords: choroid plexus, circadian rhythm, membrane transporters, sex hormones
Procedia PDF Downloads 171248 HIV-1 Nef Mediates Host Invasion by Differential Expression of Alpha-Enolase
Authors: Reshu Saxena, R. K. Tripathi
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HIV-1 transmission and spread involves significant host-virus interaction. Potential targets for prevention of HIV-1 lies at the site of mucosal barriers. Thus a better understanding of how HIV-1 infects target cells at such sites and lead their invasion is required, with prime focus on the host determinants regulating HIV-1 spread. HIV-1 Nef is important for viral infectivity and pathogenicity. It promotes HIV-1 replication, facilitating immune evasion by interacting with various host factors and altering cellular pathways via multiple protein-protein interactions. In this study nef was sequenced from HIV-1 patients, and showed specific mutations revealing sequence variability in nef. To explore the difference in Nef functionality based on sequence variability we have studied the effects of HIV-1 Nef in human SupT1 T cell line and (THP-1) monocyte-macrophage cell lines through proteomics approach. 2D-Gel Electrophoresis in control and Nef-transfected SupT1 cells demonstrated several differentially expressed proteins with significant modulation of alpha-enolase. Through further studies, effects of Nef on alpha-enolase regulation were found to be cell lineage-specific, being stimulatory in macrophages/monocytes, inhibitory in T cells and without effect in HEK-293 cells. Cell migration and invasion studies were employed to determine biological function affected by Nef mediated regulation of alpha-enolase. Cell invasion was enhanced in THP-1 cells but was inhibited in SupT1 cells by wildtype nef. In addition, the modulation of enolase and cell invasion remained unaffected by a unique nef variant. These results indicated that regulation of alpha-enolase expression and invasive property of host cells by Nef is sequence specific, suggesting involvement of a particular motif of Nef. To precisely determine this site, we designed a heptapeptide including the suggested alpha-enolase regulating sequence of nef and a nef mutant with deletion of this site. Macrophages/monocytes being the major cells affected by HIV-1 at mucosal barriers, were particularly investigated by the nef mutant and peptide. Both the nef mutant and heptapeptide led to inhibition of enhanced enolase expression and increased invasiveness in THP-1 cells. Together, these findings suggest a possible mechanism of host invasion by HIV-1 through Nef mediated regulation of alpha-enolase and identifies a potential therapeutic target for HIV-1 entry at mucosal barriers.Keywords: HIV-1 Nef, nef variants, host-virus interaction, tissue invasion
Procedia PDF Downloads 4131247 The Correlation between the Anxiety of the Family Members of the Patients Referring to the Emergency Department and Their Views on the Communication Skills of Nurses
Authors: Mahnaz Seyedoshohadaee
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Background and Aims: Hospitalization of one of the family members in the hospital, especially in the emergency department, causes anxiety and psychological problems in family members and others. The way nurses interact with patients and their companions can play an important role in controlling and managing their anxiety. This study aims to determine the relationship between the anxiety of family members of patients referring to emergency departments and their views on the communication skills of nurses. Materials and Methods: The current research was a descriptive-correlation cross-sectional study on 263 family members of patients referred to the department. The emergency of two selected medical training centers affiliated with Iran University of Medical Sciences was performed. The samples were selected continuously in 2018 based on the inclusion criteria. Information was collected using the Health Communication Questionnaire (HCCQ) and Beck Anxiety Questionnaire (BAI). To analyze the data, Pearson's correlation coefficient, independent t-tests, analysis of variance, and Kruskal-Wallis were used at a significance level of 0.05. The data was analyzed using SPSS version 16 statistical software. Results: The mean score of communication skills of emergency department nurses from the point of view of patients' companions was at a low level (74.36 with a standard deviation of 3.7). 3.75% of patients' companions had anxiety at a mild level. There was no statistically significant correlation between the anxieties of the patient's companions. The anxiety of the patient's companions had a statistically significant relationship with the educational level (P=0.039), economic status (P=0.033), and family relationship with the patient (P=0.001). Also, the average anxiety score in children was significantly higher than that of patients' wives (P=0.008). The triage level of the patient also had a statistically significant relationship with the anxiety of the patient's companions (P>0.001). Conclusion: Most of the family members of the patients referred to the emergency room experienced mild anxiety. Also, from their point of view, the communication skills of emergency nurses were at a weak level. Despite the fact that there was no statistically significant relationship between the patient's family member's anxiety and their opinion about nurses' communication skills in this study, it seems that the weak communication skills of nurses from the patient's family member's point of view need special attention. The results of the present study can provide the necessary grounds for planning to improve the communication skills of nurses and also control the anxiety of patient caregivers through in-service training or other incentive mechanisms.Keywords: anxiety, family, emergency department, communication skills, nurse
Procedia PDF Downloads 601246 Seismic Retrofit of Tall Building Structure with Viscous, Visco-Elastic, Visco-Plastic Damper
Authors: Nicolas Bae, Theodore L. Karavasilis
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Increasingly, a large number of new and existing tall buildings are required to improve their resilient performance against strong winds and earthquakes to minimize direct, as well as indirect damages to society. Those advent stationary functions of tall building structures in metropolitan regions can be severely hazardous, in socio-economic terms, which also increase the requirement of advanced seismic performance. To achieve these progressive requirements, the seismic reinforcement for some old, conventional buildings have become enormously costly. The methods of increasing the buildings’ resilience against wind or earthquake loads have also become more advanced. Up to now, vibration control devices, such as the passive damper system, is still regarded as an effective and an easy-to-install option, in improving the seismic resilience of buildings at affordable prices. The main purpose of this paper is to examine 1) the optimization of the shape of visco plastic brace damper (VPBD) system which is one of hybrid damper system so that it can maximize its energy dissipation capacity in tall buildings against wind and earthquake. 2) the verification of the seismic performance of the visco plastic brace damper system in tall buildings; up to forty-storey high steel frame buildings, by comparing the results of Non-Linear Response History Analysis (NLRHA), with and without a damper system. The most significant contribution of this research is to introduce the optimized hybrid damper system that is adequate for high rise buildings. The efficiency of this visco plastic brace damper system and the advantages of its use in tall buildings can be verified since tall buildings tend to be affected by wind load at its normal state and also by earthquake load after yielding of steel plates. The modeling of the prototype tall building will be conducted using the Opensees software. Three types of modeling were used to verify the performance of the damper (MRF, MRF with visco-elastic, MRF with visco-plastic model) 22-set seismic records used and the scaling procedure was followed according to the FEMA code. It is shown that MRF with viscous, visco-elastic damper, it is superior effective to reduce inelastic deformation such as roof displacement, maximum story drift, roof velocity compared to the MRF only.Keywords: tall steel building, seismic retrofit, viscous, viscoelastic damper, performance based design, resilience based design
Procedia PDF Downloads 1931245 Comparison of Early Post-operative Outcomes of Cardiac Surgery Patients Who Have Had Blood Transfusion Based on Fixed Cut-off Point versus of Change in Percentage of Basic Hematocrit Levels
Authors: Khosro Barkhordari, Fateme Sadr, Mina Pashang
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Back ground: Blood transfusion is one of the major issues in cardiac surgery patients. Transfusing patients based on fixed cut-off points of hemoglobin is the current protocol in most institutions. The hemoglobin level of 7- 10 has been suggested for blood transfusion in cardiac surgery patients. We aimed to evaluate if blood transfusion based on change in percentage of hematocrit has different outcomes. Methods: In this retrospective cohort study, we investigated the early postoperative outcome of cardiac surgery patients who received blood transfusions at Tehran Heart Center Hospital, IRAN. We reviewed and analyzed the basic characteristics and clinical data of 700 patients who met our exclusion and inclusion criteria. The two groups of blood transfused patients were compared, those who have 30-50 percent decrease in basal hematocrit versus those with 10 -29 percent decrease. Results: This is ongoing study, and the results would be completed in two weeks after analysis of the date. Conclusion: Early analysis has shown no difference in early post-operative outcomes between the two groups, but final analysis will be completed in two weeks. 1-Department of Anesthesiology and Critical Care, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, IRAN 2- Department of Research, Tehran Heart Center, Tehran, IRAN Quantitative variables were compared using the Student t-test or the Mann‐Whitney U test, as appropriate, while categorical variables were compared using the χ2 or the Fisher exact test, as required. Our intention was to compare the early postoperative outcomes between the two groups, which include 30 days mortality, Length of ICU stay, Length of hospital stay, Intubation time, Infection rate, acute kidney injury, and respiratory complications. The main goal was to find if transfusing blood based on changes in hematocrit from a basal level was better than to fixed cut-off point regarding early post-operative outcomes. This has not been studied enough and may need randomized control trials.Keywords: post-operative, cardiac surgery, outcomes, blood transfusion
Procedia PDF Downloads 871244 Implementing Online Blogging in Specific Context Using Process-Genre Writing Approach in Saudi EFL Writing Class to Improve Writing Learning and Teaching Quality
Authors: Sultan Samah A. Alenezi
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Many EFL teachers are eager to look into the best way to suit the needs of their students in EFL writing courses. Numerous studies suggest that online blogging may present a social interaction opportunity for EFL writing students. Additionally, it can foster peer collaboration and social support in the form of scaffolding, which, when viewed from the perspective of socio-cultural theory, can boost social support and foster the development of students' writing abilities. This idea is based on Vygotsky's theories, which emphasize how collaboration and social interaction facilitate effective learning. In Saudi Arabia, students are taught to write using conventional methods that are totally under the teacher's control. Without any peer contact or cooperation, students are spoon-fed in a passive environment. This study included the cognitive processes of the genre-process approach into the EFL writing classroom to facilitate the use of internet blogging in EFL writing education. Thirty second-year undergraduate students from the Department of Languages and Translation at a Saudi college participated in this study. This study employed an action research project that blended qualitative and quantitative methodologies to comprehend Saudi students' perceptions and experiences with internet blogging in an EFL process-genre writing classroom. It also looked at the advantages and challenges people faced when blogging. They included a poll, interviews, and blog postings made by students. The intervention's outcomes showed that merging genre-process procedures with blogging was a successful tactic, and the Saudi students' perceptions of this method of online blogging for EFL writing were quite positive. The socio-cultural theory constructs that Vygotsky advocates, such as scaffolding, collaboration, and social interaction, were also improved by blogging. These elements demonstrated the improvement in the students' written, reading, social, and collaborative thinking skills, as well as their positive attitudes toward English-language writing. But the students encountered a variety of problems that made blogging difficult for them. These problems ranged from technological ones, such sluggish internet connections, to learner inadequacies, like a lack of computer know-how and ineffective time management.Keywords: blogging, process-gnere approach, saudi learenrs, writing quality
Procedia PDF Downloads 1221243 Fabrication and Characterisation of Additive Manufactured Ti-6Al-4V Parts by Laser Powder Bed Fusion Technique
Authors: Norica Godja, Andreas Schindel, Luka Payrits, Zsolt Pasztor, Bálint Hegedüs, Petr Homola, Jan Horňas, Jiří Běhal, Roman Ruzek, Martin Holzleitner, Sascha Senck
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In order to reduce fuel consumption and CO₂ emissions in the aviation sector, innovative solutions are being sought to reduce the weight of aircraft, including additive manufacturing (AM). Of particular importance are the excellent mechanical properties that are required for aircraft structures. Ti6Al4V alloys, with their high mechanical properties in relation to weight, can reduce the weight of aircraft structures compared to structures made of steel and aluminium. Currently, conventional processes such as casting and CNC machining are used to obtain the desired structures, resulting in high raw material removal, which in turn leads to higher costs and impacts the environment. Additive manufacturing (AM) offers advantages in terms of weight, lead time, design, and functionality and enables the realisation of alternative geometric shapes with high mechanical properties. However, there are currently technological shortcomings that have led to AM not being approved for structural components with high safety requirements. An assessment of damage tolerance for AM parts is required, and quality control needs to be improved. Pores and other defects cannot be completely avoided at present, but they should be kept to a minimum during manufacture. The mechanical properties of the manufactured parts can be further improved by various treatments. The influence of different treatment methods (heat treatment, CNC milling, electropolishing, chemical polishing) and operating parameters were investigated by scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM/EDX), X-ray diffraction (XRD), electron backscatter diffraction (EBSD) and measurements with a focused ion beam (FIB), taking into account surface roughness, possible anomalies in the chemical composition of the surface and possible cracks. The results of the characterisation of the constructed and treated samples are discussed and presented in this paper. These results were generated within the framework of the 3TANIUM project, which is financed by EU with the contract number 101007830.Keywords: Ti6Al4V alloys, laser powder bed fusion, damage tolerance, heat treatment, electropolishing, potential cracking
Procedia PDF Downloads 861242 Identifying Diabetic Retinopathy Complication by Predictive Techniques in Indian Type 2 Diabetes Mellitus Patients
Authors: Faiz N. K. Yusufi, Aquil Ahmed, Jamal Ahmad
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Predicting the risk of diabetic retinopathy (DR) in Indian type 2 diabetes patients is immensely necessary. India, being the second largest country after China in terms of a number of diabetic patients, to the best of our knowledge not a single risk score for complications has ever been investigated. Diabetic retinopathy is a serious complication and is the topmost reason for visual impairment across countries. Any type or form of DR has been taken as the event of interest, be it mild, back, grade I, II, III, and IV DR. A sample was determined and randomly collected from the Rajiv Gandhi Centre for Diabetes and Endocrinology, J.N.M.C., A.M.U., Aligarh, India. Collected variables include patients data such as sex, age, height, weight, body mass index (BMI), blood sugar fasting (BSF), post prandial sugar (PP), glycosylated haemoglobin (HbA1c), diastolic blood pressure (DBP), systolic blood pressure (SBP), smoking, alcohol habits, total cholesterol (TC), triglycerides (TG), high density lipoprotein (HDL), low density lipoprotein (LDL), very low density lipoprotein (VLDL), physical activity, duration of diabetes, diet control, history of antihypertensive drug treatment, family history of diabetes, waist circumference, hip circumference, medications, central obesity and history of DR. Cox proportional hazard regression is used to design risk scores for the prediction of retinopathy. Model calibration and discrimination are assessed from Hosmer Lemeshow and area under receiver operating characteristic curve (ROC). Overfitting and underfitting of the model are checked by applying regularization techniques and best method is selected between ridge, lasso and elastic net regression. Optimal cut off point is chosen by Youden’s index. Five-year probability of DR is predicted by both survival function, and Markov chain two state model and the better technique is concluded. The risk scores developed can be applied by doctors and patients themselves for self evaluation. Furthermore, the five-year probabilities can be applied as well to forecast and maintain the condition of patients. This provides immense benefit in real application of DR prediction in T2DM.Keywords: Cox proportional hazard regression, diabetic retinopathy, ROC curve, type 2 diabetes mellitus
Procedia PDF Downloads 1871241 Hepatitis B, Hepatitis C and HIV Infections and Associated Risk Factors among Substance Abusers in Mekelle Substance Users Treatment and Rehabilitation Centers, Tigrai, Northern Ethiopia
Authors: Tadele Araya, Tsehaye Asmelash, Girmatsion Fiseha
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Background: Hepatitis B virus (HBV), Hepatitis C virus (HCV) and Human Immunodeficiency Virus (HIV) constitute serious healthcare problems worldwide. Blood-borne pathogens HBV, HCV and HIV are commonly associated with infections among substance or Injection Drug Users (IDUs). The objective of this study was to determine the prevalence of HBV, HCV, and HIV infections among substance users in Mekelle Substance users Treatment and Rehabilitation Centers. Methods: A cross-sectional study design was used from Dec 2020 to Sep / 2021 to conduct the study. A total of 600 substance users were included. Data regarding the socio-demographic, clinical and sexual behaviors of the substance users were collected using a structured questionnaire. For laboratory analysis, 5-10 ml of venous blood was taken from the substance users. The laboratory analysis was performed by Enzyme-Linked Immunosorbent Assay (ELISA) at Mekelle University, Department of Medical Microbiology and Immunology Research Laboratory. The Data was analyzed using SPSS and Epi-data. The association of variables with HBV, HCV and HIV infections was determined using multivariate analysis and a P value < 0.05 was considered statistically significant. Result: The overall prevalence rate of HBV, HCV and HIV infections were 10%, 6.6%, and 7.5%, respectively. The mean age of the study participants was 28.12 ± 6.9. A higher prevalence of HBV infection was seen in participants who were users of drug injections and in those who were infected with HIV. HCV was comparatively higher in those who had a previous history of unsafe surgical procedures than their counterparts. Homeless participants were highly exposed to HCV and HIV infections than their counterparts. The HBV/HIV Co-infection prevalence was 3.5%. Those doing unprotected sexual practices [P= 0.03], Injection Drug users [P= 0.03], those who had an HBV-infected person in their family [P=0.02], infected with HIV [P= 0.025] were statistically associated with HBV infection. HCV was significantly associated with Substance users and previous history of unsafe surgical procedures [p=0.03, p=0.04), respectively. HIV was significantly associated with unprotected sexual practices and being homeless [p=0.045, p=0.05) respectively. Conclusion-The highly prevalent viral infection was HBV compared to others. There was a High prevalence of HBV/HIV co-infection. The presence of HBV-infected persons in a family, unprotected sexual practices and sharing of needles for drug injection were the risk factors associated with HBV, HIV, and HCV. Continuous health education and screening of the viral infection coupled with medical and psychological treatment is mandatory for the prevention and control of the infections.Keywords: hepatitis b virus, hepatitis c virus, HIV, substance users
Procedia PDF Downloads 871240 A Bottom-Up Approach for the Synthesis of Highly Ordered Fullerene-Intercalated Graphene Hybrids
Authors: A. Kouloumpis, P. Zygouri, G. Potsi, K. Spyrou, D. Gournis
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Much of the research effort on graphene focuses on its use as building block for the development of new hybrid nanostructures with well-defined dimensions and behavior suitable for applications among else in gas storage, heterogeneous catalysis, gas/liquid separations, nanosensing and biology. Towards this aim, here we describe a new bottom-up approach, which combines the self-assembly with the Langmuir Schaefer technique, for the production of fullerene-intercalated graphene hybrid materials. This new method uses graphene nanosheets as a template for the grafting of various fullerene C60 molecules (pure C60, bromo-fullerenes, C60Br24, and fullerols, C60(OH)24) in a bi-dimensional array, and allows for perfect layer-by-layer growth with control at the molecular level. Our film preparation approach involves a bottom-up layer-by-layer process that includes the formation of a hybrid organo-graphene Langmuir film hosting fullerene molecules within its interlayer spacing. A dilute water solution of chemically oxidized graphene (GO) was used as subphase on the Langmuir-Blodgett deposition system while an appropriate amino surfactant (that binds covalently with the GO) was applied for the formation of hybridized organo-GO. After the horizontal lift of a hydrophobic substrate, a surface modification of the GO platelets was performed by bringing the surface of the transferred Langmuir film in contact with a second amino surfactant solution (capable to interact strongly with the fullerene derivatives). In the final step, the hybrid organo-graphene film was lowered in the solution of the appropriate fullerene derivative. Multilayer films were constructed by repeating this procedure. Hybrid fullerene-based thin films deposited on various hydrophobic substrates were characterized by X-ray diffraction (XRD) and X-ray reflectivity (XRR), FTIR, and Raman spectroscopies, Atomic Force Microscopy, and optical measurements. Acknowledgments. This research has been co‐financed by the European Union (European Social Fund – ESF) and Greek national funds through the Operational Program "Education and Lifelong Learning" of the National Strategic Reference Framework (NSRF)‐Research Funding Program: THALES. Investing in knowledge society through the European Social Fund (no. 377285).Keywords: hybrids, graphene oxide, fullerenes, langmuir-blodgett, intercalated structures
Procedia PDF Downloads 3271239 Effects of Renin Angiotensin Pathway Inhibition on Efficacy of Anti-PD-1/PD-L1 Treatment in Metastatic Cancer
Authors: Philip Friedlander, John Rutledge, Jason Suh
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Inhibition of programmed death-1 (PD-1) or its ligand PD-L1 confers therapeutic efficacy in a wide range of solid tumor malignancies. Primary or acquired resistance can develop through activation of immunosuppressive immune cells such as tumor-associated macrophages. The renin angiotensin system (RAS) systemically regulates fluid and sodium hemodynamics, but components are expressed on and regulate the activity of immune cells, particularly of myeloid lineage. We hypothesized that inhibition of RAS would improve the efficacy of PD-1/PD-L-1 treatment. A retrospective analysis was performed through a chart review of patients with solid metastatic malignancies treated with a PD-1/PD-L1 inhibitor between 1/2013 and 6/2019 at Valley Hospital, a community hospital in New Jersey, USA. Efficacy was determined by medical oncologist documentation of clinical benefit in visit notes and by the duration of time on immunotherapy treatment. The primary endpoint was the determination of efficacy differences in patients treated with an inhibitor of RAS ( ace inhibitor, ACEi, or angiotensin blocker, ARB) compared to patients not treated with these inhibitors. To control for broader antihypertensive effects, efficacy as a function of treatment with beta blockers was assessed. 173 patients treated with PD-1/PD-L-1 inhibitors were identified of whom 52 were also treated with an ACEi or ARB. Chi-square testing revealed a statistically significant relationship between being on an ACEi or ARB and efficacy to PD-1/PD-L-1 therapy (p=0.001). No statistically significant relationship was seen between patients taking or not taking beta blocker antihypertensives (p= 0.33). Kaplan-Meier analysis showed statistically significant improvement in the duration of therapy favoring patients concomitantly treated with ACEi or ARB compared to patients not exposed to antihypertensives and to those treated with beta blockers. Logistic regression analysis revealed that age, gender, and cancer type did not have significant effects on the odds of experiencing clinical benefit (p=0.74, p=0.75, and p=0.81, respectively). We conclude that retrospective analysis of the treatment of patients with solid metastatic tumors with anti-PD-1/PD-L1 in a community setting demonstrates greater clinical benefit in the context of concomitant ACEi or ARB inhibition, irrespective of gender or age. This data supports the development of prospective assessment through randomized clinical trials.Keywords: angiotensin, cancer, immunotherapy, PD-1, efficacy
Procedia PDF Downloads 781238 Anticancer Activity of Milk Fat Rich in Conjugated Linoleic Acid Against Ehrlich Ascites Carcinoma Cells in Female Swiss Albino Mice
Authors: Diea Gamal Abo El-Hassan, Salwa Ahmed Aly, Abdelrahman Mahmoud Abdelgwad
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The major conjugated linoleic acid (CLA) isomers have anticancer effect, especially breast cancer cells, inhibits cell growth and induces cell death. Also, CLA has several health benefits in vivo, including antiatherogenesis, antiobesity, and modulation of immune function. The present study aimed to assess the safety and anticancer effects of milk fat CLA against in vivo Ehrlich ascites carcinoma (EAC) in female Swiss albino mice. This was based on acute toxicity study, detection of the tumor growth, life span of EAC bearing hosts, and simultaneous alterations in the hematological, biochemical, and histopathological profiles. Materials and Methods: One hundred and fifty adult female mice were equally divided into five groups. Groups (1-2) were normal controls, and Groups (3-5) were tumor transplanted mice (TTM) inoculated intraperitoneally with EAC cells (2×106 /0.2 mL). Group (3) was (TTM positive control). Group (4) TTM fed orally on balanced diet supplemented with milk fat CLA (40 mg CLA/kg body weight). Group (5) TTM fed orally on balanced diet supplemented with the same level of CLA 28 days before tumor cells inoculation. Blood samples and specimens from liver and kidney were collected from each group. The effect of milk fat CLA on the growth of tumor, life span of TTM, and simultaneous alterations in the hematological, biochemical, and histopathological profiles were examined. Results: For CLA treated TTM, significant decrease in tumor weight, ascetic volume, viable Ehrlich cells accompanied with increase in life span were observed. Hematological and biochemical profiles reverted to more or less normal levels and histopathology showed minimal effects. Conclusion: The present study proved the safety and anticancer efficiency of milk fat CLA and provides a scientific basis for its medicinal use as anticancer attributable to the additive or synergistic effects of its isomers.Keywords: anticancer activity, conjugated linoleic acid, Ehrlich ascites carcinoma, % increase in life span, mean survival time, tumor transplanted mice.
Procedia PDF Downloads 931237 An ICF Framework for Game-Based Experiences in Geriatric Care
Authors: Marlene Rosa, Susana Lopes
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Board games have been used for different purposes in geriatric care, demonstrating good results for health in general. However, there is not a conceptual framework that can help professionals and researchers in this area to design intervention programs or to think about future studies in this area. The aim of this study was to provide a pilot collection of board games’ serious purposes in geriatric care, using a WHO framework for health and disability. Study cases were developed in seven geriatric residential institutions from the center region in Portugal that are included in AGILAB program. The AGILAB program is a serious game-based method to train and spread out the implementation of board games in geriatric care. Each institution provides 2-hours/week of experiences using TATI Hand Game for serious purposes and then fulfill questions about a study-case (player characteristics; explain changes in players health according to this game experience). Two independent researchers read the information and classified it according to the International Classification for Functioning and Disability (ICF) categories. Any discrepancy was solved in a consensus meeting. Results indicate an important variability in body functions and structures: specific mental functions (e.g., b140 Attention functions, b144 Memory functions), b156 Perceptual functions, b2 sensory functions and pain (e.g., b230 Hearing functions; b265 Touch function; b280 Sensation of pain), b7 neuromusculoskeletal and movement-related functions (e.g., b730 Muscle power functions; b760 Control of voluntary movement functions; b710 Mobility of joint functions). Less variability was found in activities and participation domains, such as purposeful sensory experiences (d110-d129) (e.g., d115 Listening), communication (d3), d710 basic interpersonal interactions, d920 recreation and leisure (d9200 Play; d9205 Socializing). Concluding, this framework designed from a brief gamed-based experience includes mental, perceptual, sensory, neuromusculoskeletal, and movement-related functions and participation in sensory, communication, and leisure domains. More studies, including different experiences and a high number of users, should be developed to provide a more comprehensive ICF framework for game-based experiences in geriatric care.Keywords: board game, aging, framework, experience
Procedia PDF Downloads 1271236 The Non-Motor Symptoms of Filipino Patients with Parkinson’s Disease
Authors: Cherrie Mae S. Sia, Noel J. Belonguel, Jarungchai Anton S. Vatanagul
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Background: Parkinson’s disease (PD) is a chronic progressive, neurodegenerative disorder known for its motor symptoms such as bradykinesia, resting tremor, muscle rigidity, and postural instability. Patients with PD also experience non-motor symptoms (NMS) such as depression, fatigue, and sleep disturbances that are most of the time unrecognized by clinicians. This may be due to the lack of spontaneous reports from the patients or partly because of the lack of systematic questioning from the healthcare professional. There is limited data with regards to these NMS especially that of Filipino patients with PD. Objectives: This study aims to determine the non-motor symptoms of Filipino patients with Parkinson’s disease. Materials and Methods: This is a prospective, cohort study involving thirty-four patients of Filipino-descent diagnosed with PD in three out-patient clinics in Cebu City from April to September 2014. Each patient was interviewed using the Non-Motor Symptom Scale (NMSS). A Cebuano version of the NMSS was also provided for the non-English speaking patients. Interview time was approximately ten to fifteen minutes for each respondent. Results: Of the thirty-four patients with Parkinson’s disease, majority was noted to be males (N=19) and the disease was noted to be more prevalent in patients with a mean age of 62 (SD±9) years old. Hypertension (59%) and diabetes mellitus (29%) were the common co-morbidities in the study population. All patients presented more than one NMS, with insomnia (41.2%), poor memory (23.5%) and depression (14.7%) being the first non-motor symptoms to occur. Symptoms involving mood/cognition (mean=2.21), and attention/memory (mean=2.05) were noted to be the most frequent and of moderate severity. Based on the NMSS, the symptoms that were noted to be mild and often to occur were those that involved the mood/cognition (score=3.84), attention/memory (score=3.50), and sleep/fatigue (score=3.00) domains. Levodopa-Carbidopa, Ropinirole, and Pramipexole were the most frequently used medications in the study population. Conclusion: Non-motor symptoms (NMS) are common in patients with Parkinson’s disease (PD). They appear at the time of diagnosis of PD or even before the motor symptoms manifest. The earliest non-motor symptoms to occur are insomnia, poor memory, and depression. Those pertaining to mood/cognition and attention/memory are the most frequent NMS and they are of moderate severity. Identifying these NMS by doing a questionnaire-guided interview such as the Non-Motor Symptom Scale (NMSS) before they can become more severe and affect the patient’s quality of life is a must for every clinician caring for a PD patient. Early treatment and control of these NMS can then be given, hence, improving the patient’s outcome and prognosis.Keywords: non motor symptoms, Parkinson's Disease, insomnia, depression
Procedia PDF Downloads 4481235 Exhaled Breath Condensate in Lung Cancer: A Non-Invasive Sample for Easier Mutations Detection by Next Generation Sequencing
Authors: Omar Youssef, Aija Knuuttila, Paivi Piirilä, Virinder Sarhadi, Sakari Knuutila
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Exhaled breath condensate (EBC) is a unique sample that allows studying different genetic changes in lung carcinoma through a non-invasive way. With the aid of next generation sequencing (NGS) technology, analysis of genetic mutations has been more efficient with increased sensitivity for detection of genetic variants. In order to investigate the possibility of applying this method for cancer diagnostics, mutations in EBC DNA from lung cancer patients and healthy individuals were studied by using NGS. The key aim is to assess the feasibility of using this approach to detect clinically important mutations in EBC. EBC was collected from 20 healthy individuals and 9 lung cancer patients (four lung adenocarcinomas, four 8 squamous cell carcinoma, and one case of mesothelioma). Mutations in hotpot regions of 22 genes were studied by using Ampliseq Colon and Lung cancer panel and sequenced on Ion PGM. Results demonstrated that all nine patients showed a total of 19 cosmic mutations in APC, BRAF, EGFR, ERBB4, FBXW7, FGFR1, KRAS, MAP2K1, NRAS, PIK3CA, PTEN, RET, SMAD4, and TP53. In controls, 15 individuals showed 35 cosmic mutations in BRAF, CTNNB1, DDR2, EGFR, ERBB2, FBXW7, FGFR3, KRAS, MET, NOTCH1, NRAS, PIK3CA, PTEN, SMAD4, and TP53. Additionally, 45 novel mutations not reported previously were also seen in patients’ samples, and 106 novel mutations were seen in controls’ specimens. KRAS exon 2 mutations G12D was identified in one control specimen with mutant allele fraction of 6.8%, while KRAS G13D mutation seen in one patient sample showed mutant allele fraction of 17%. These findings illustrate that hotspot mutations are present in DNA from EBC of both cancer patients and healthy controls. As some of the cosmic mutations were seen in controls too, no firm conclusion can be drawn on the clinical importance of cosmic mutations in patients. Mutations reported in controls could represent early neoplastic changes or normal homeostatic process of apoptosis occurring in lung tissue to get rid of mutant cells. At the same time, mutations detected in patients might represent a non-invasive easily accessible way for early cancer detection. Follow up of individuals with important cancer mutations is necessary to clarify the significance of these mutations in both healthy individuals and cancer patients.Keywords: exhaled breath condensate, lung cancer, mutations, next generation sequencing
Procedia PDF Downloads 1771234 On the Other Side of Shining Mercury: In Silico Prediction of Cold Stabilizing Mutations in Serine Endopeptidase from Bacillus lentus
Authors: Debamitra Chakravorty, Pratap K. Parida
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Cold-adapted proteases enhance wash performance in low-temperature laundry resulting in a reduction in energy consumption and wear of textiles and are also used in the dehairing process in leather industries. Unfortunately, the possible drawbacks of using cold-adapted proteases are their instability at higher temperatures. Therefore, proteases with broad temperature stability are required. Unfortunately, wild-type cold-adapted proteases exhibit instability at higher temperatures and thus have low shelf lives. Therefore, attempts to engineer cold-adapted proteases by protein engineering were made previously by directed evolution and random mutagenesis. The lacuna is the time, capital, and labour involved to obtain these variants are very demanding and challenging. Therefore, rational engineering for cold stability without compromising an enzyme's optimum pH and temperature for activity is the current requirement. In this work, mutations were rationally designed with the aid of high throughput computational methodology of network analysis, evolutionary conservation scores, and molecular dynamics simulations for Savinase from Bacillus lentus with the intention of rendering the mutants cold stable without affecting their temperature and pH optimum for activity. Further, an attempt was made to incorporate a mutation in the most stable mutant rationally obtained by this method to introduce oxidative stability in the mutant. Such enzymes are desired in detergents with bleaching agents. In silico analysis by performing 300 ns molecular dynamics simulations at 5 different temperatures revealed that these three mutants were found to be better in cold stability compared to the wild type Savinase from Bacillus lentus. Conclusively, this work shows that cold adaptation without losing optimum temperature and pH stability and additionally stability from oxidative damage can be rationally designed by in silico enzyme engineering. The key findings of this work were first, the in silico data of H5 (cold stable savinase) used as a control in this work, corroborated with its reported wet lab temperature stability data. Secondly, three cold stable mutants of Savinase from Bacillus lentus were rationally identified. Lastly, a mutation which will stabilize savinase against oxidative damage was additionally identified.Keywords: cold stability, molecular dynamics simulations, protein engineering, rational design
Procedia PDF Downloads 1421233 Ameliorative Effect of Curcuma Longa against Arsenic Induced Reproductive Toxicity in Charles Foster Rats
Authors: Shazia Naheed Akhter, Rekha Kumari
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An estimated 70 million population are exposed to arsenic poisoning in India in recent times. Arsenic contamination in the groundwater has caused serious health hazards among the exposed population. In Bihar, the first district was Bhojpur, where arsenic causing health issues were reported in 2002. Presently, there are 18 districts that are reported arsenic poisoning in the groundwater. The exposed population is firstly diseased with various symptoms such as skin manifestations, loss of appetite, constipation, hormonal disorders, etc. The long duration exposure has led to cause infertility in the male subjects. The present study thus aims to develop the antidote against arsenic-induced male reproductive toxicity in animal models. The study was carried out on Charles Foster Rats after the approval from Institutional Animal Ethics Committee. A total of n=18 rats (12 weeks old) of an average weight of 160 ± 20 g were used for the study. The study group included n=6 control and n= 12 treated with sodium arsenite orally at the dose of 8mg/Kg b.w daily for 40 days. The n= 6 animals were dissected and the rest n=6 was administered orally with Curcuma longa rhizome ethanolic extract at the dose of 600mg/Kg b.w per day for 40 days. At the end of the entire experiment, all the animals were dissected out and their reproductive organs were taken out, especially epididymis for sperm counts, sperm motility, sperm mortality, sperm morphology. The blood samples were collected for the hormonal assay (testosterone and luteinizing hormone), as well as for hematological and biochemical analysis. The study showed a high magnitude of degeneration in the reproductive organs of the rats in the arsenic-treated group. There were degenerative fluctuations in the sperm counts, sperm motility, sperm mortality, sperm morphology and in the hormonal parameters, as well as in the hematological and biochemical parameters in the arsenic-treated rats. But, after the administration of Curcuma longa, there was significant amelioration in all these parameters. Therefore, the present study shows that Curcuma longa plays a vital role to combat arsenic-induced male reproductive toxicity.Keywords: sodium arsenite, Charles foster rats, ethanolic rhizome extract of curcuma longa, male reproductive toxicity, amelioration
Procedia PDF Downloads 2291232 Transformation of the Institutionality of International Cooperation in Ecuador from 2007 to 2017: 2017: A Case of State Identity Affirmation through Role Performance
Authors: Natalia Carolina Encalada Castillo
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As part of an intended radical policy change compared to former administrations in Ecuador, the transformation of the institutionality of international cooperation during the period of President Rafael Correa was considered as a key element for the construction of the state of 'Good Living'. This intention led to several regulatory changes in the reception of cooperation for development, and even the departure of some foreign cooperation agencies. Moreover, Ecuador launched the initiative to become a donor of cooperation towards other developing countries through the ‘South-South Cooperation’ approach. All these changes were institutionalized through the Ecuadorian System of International Cooperation as a new framework to establish rules and policies that guarantee a sovereign management of foreign aid. Therefore, this research project has been guided by two questions: What were the factors that motivated the transformation of the institutionality of international cooperation in Ecuador from 2007 to 2017? and, what were the implications of this transformation in terms of the international role of the country? This paper seeks to answer these questions through Role Theory within a Constructivist meta-theoretical perspective, considering that in this case, changes at the institutional level in the field of cooperation, responded not only to material motivations but also to interests built on the basis of a specific state identity. The latter was only possible to affirm through specific roles such as ‘sovereign recipient of cooperation’ as well as ‘donor of international cooperation’. However, the performance of these roles was problematic as they were not easily accepted by the other actors in the international arena or in the domestic level. In terms of methodology, these dynamics are analyzed in a qualitative way mainly through interpretive analysis of the discourse of high-level decision-makers from Ecuador and other cooperation actors. Complementary to this, document-based research of relevant information as well as interviews have been conducted. Finally, it is concluded that even if material factors such as infrastructure needs, trade and investment interests, as well as reinforcement of state control and monitoring of cooperation flows, motivated the institutional transformation of international cooperation in Ecuador; the essential basis of these changes was the search for a new identity for the country to be projected in the international arena. This identity started to be built but continues to be unstable. Therefore, it is important to potentiate the achievements of the new international cooperation policies, and review their weaknesses, so that non-reimbursable cooperation funds received as well as ‘South-South cooperation’ actions, contribute effectively to national objectives.Keywords: Ecuador, international cooperation, Role Theory, state identity
Procedia PDF Downloads 2161231 Analysis of Constraints and Opportunities in Dairy Production in Botswana
Authors: Som Pal Baliyan
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Dairy enterprise has been a major source of employment and income generation in most of the economies worldwide. Botswana government has also identified dairy as one of the agricultural sectors towards diversification of the mineral dependent economy of the country. The huge gap between local demand and supply of milk and milk products indicated that there are not only constraints but also; opportunities exist in this sub sector of agriculture. Therefore, this study was an attempt to identify constraints and opportunities in dairy production industry in Botswana. The possible ways to mitigate the constraints were also identified. The findings should assist the stakeholders especially, policy makers in the formulation of effective policies for the growth of dairy sector in the country. This quantitative study adopted a survey research design. A final survey followed by a pilot survey was conducted for data collection. The purpose of the pilot survey was to collect basic information on the nature and extent of the constraints, opportunities and ways to mitigate the constraints in dairy production. Based on the information from pilot survey, a four point Likert’s scale type questionnaire was constructed, validated and tested for its reliability. The data for the final survey were collected from purposively selected twenty five dairy farms. The descriptive statistical tools were employed to analyze data. Among the twelve constraints identified; high feed costs, feed shortage and availability, lack of technical support, lack of skilled manpower, high prevalence of pests and diseases and, lack of dairy related technologies were the six major constraints in dairy production. Grain feed production, roughage feed production, manufacturing of dairy feed, establishment of milk processing industry and, development of transportation systems were the five major opportunities among the eight opportunities identified. Increasing production of animal feed locally, increasing roughage feed production locally, provision of subsidy on animal feed, easy access to sufficient financial support, training of the farmers and, effective control of pests and diseases were identified as the six major ways to mitigate the constraints. It was recommended that the identified constraints and opportunities as well as the ways to mitigate the constraints need to be carefully considered by the stakeholders especially, policy makers during the formulation and implementation of the policies for the development of dairy sector in Botswana.Keywords: dairy enterprise, milk production, opportunities, production constraints
Procedia PDF Downloads 4071230 Screening Maize for Compatibility with F. Oxysporum to Enhance Striga asiatica (L.) Kuntze Resistance
Authors: Admire Isaac Tichafa Shayanowako, Mark Laing, Hussein Shimelis
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Striga asiatica is among the leading abiotic constraints to maize production under small-holder farming communities in southern African. However, confirmed sources of resistance to the parasitic weed are still limited. Conventional breeding programmes have been progressing slowly due to the complex nature of the inheritance of Striga resistance, hence there is a need for more innovative approaches. This study aimed to achieve partial resistance as well as to breed for compatibility with Fusarium oxysporum fsp strigae, a soil fungus that is highly specific in its pathogenicity. The agar gel and paper roll assays in conjunction with a glass house pot trial were done to select genotypes based on their potential to stimulate germination of Striga and to test the efficacy of Fusarium oxysporum as a biocontrol agent. Results from agar gel assays showed a moderate to high potential in the release of Strigalactones among the 33 OPVs. Maximum Striga germination distances from the host root of 1.38 cm and up to 46% germination were observed in most of the populations. Considerable resistance was observed in a landrace ‘8lines’ which had the least Striga germination percentage (19%) with a maximum distance of 0.93 cm compared to the resistant check Z-DPLO-DTC1 that had 23% germination at a distance of 1.4cm. The number of fusarium colony forming units significantly deferred (P < 0.05) amongst the genotypes growing between germination papers. The number of crown roots, length of primary root and fresh weight of shoot and roots were highly correlated with concentration of fusarium macrospore counts. Pot trials showed significant differences between the fusarium coated and the uncoated treatments in terms of plant height, leaf counts, anthesis-silks intervals, Striga counts, Striga damage rating and Striga vigour. Striga emergence counts and Striga flowers were low in fusarium treated pots. Plants in fusarium treated pots had non-significant differences in height with the control treatment. This suggests that foxy 2 reduces the impact of Striga damage severity. Variability within fusarium treated genotypes with respect to traits under evaluation indicates the varying degree of compatibility with the biocontrol.Keywords: maize, Striga asiaitca, resistance, compatibility, F. oxysporum
Procedia PDF Downloads 2511229 A Decision-Support Tool for Humanitarian Distribution Planners in the Face of Congestion at Security Checkpoints: A Real-World Case Study
Authors: Mohanad Rezeq, Tarik Aouam, Frederik Gailly
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In times of armed conflicts, various security checkpoints are placed by authorities to control the flow of merchandise into and within areas of conflict. The flow of humanitarian trucks that is added to the regular flow of commercial trucks, together with the complex security procedures, creates congestion and long waiting times at the security checkpoints. This causes distribution costs to increase and shortages of relief aid to the affected people to occur. Our research proposes a decision-support tool to assist planners and policymakers in building efficient plans for the distribution of relief aid, taking into account congestion at security checkpoints. The proposed tool is built around a multi-item humanitarian distribution planning model based on multi-phase design science methodology that has as its objective to minimize distribution and back ordering costs subject to capacity constraints that reflect congestion effects using nonlinear clearing functions. Using the 2014 Gaza War as a case study, we illustrate the application of the proposed tool, model the underlying relief-aid humanitarian supply chain, estimate clearing functions at different security checkpoints, and conduct computational experiments. The decision support tool generated a shipment plan that was compared to two benchmarks in terms of total distribution cost, average lead time and work in progress (WIP) at security checkpoints, and average inventory and backorders at distribution centers. The first benchmark is the shipment plan generated by the fixed capacity model, and the second is the actual shipment plan implemented by the planners during the armed conflict. According to our findings, modeling and optimizing supply chain flows reduce total distribution costs, average truck wait times at security checkpoints, and average backorders when compared to the executed plan and the fixed-capacity model. Finally, scenario analysis concludes that increasing capacity at security checkpoints can lower total operations costs by reducing the average lead time.Keywords: humanitarian distribution planning, relief-aid distribution, congestion, clearing functions
Procedia PDF Downloads 831228 Impact of Intelligent Transportation System on Planning, Operation and Safety of Urban Corridor
Authors: Sourabh Jain, S. S. Jain
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Intelligent transportation system (ITS) is the application of technologies for developing a user–friendly transportation system to extend the safety and efficiency of urban transportation systems in developing countries. These systems involve vehicles, drivers, passengers, road operators, managers of transport services; all interacting with each other and the surroundings to boost the security and capacity of road systems. The goal of urban corridor management using ITS in road transport is to achieve improvements in mobility, safety, and the productivity of the transportation system within the available facilities through the integrated application of advanced monitoring, communications, computer, display, and control process technologies, both in the vehicle and on the road. Intelligent transportation system is a product of the revolution in information and communications technologies that is the hallmark of the digital age. The basic ITS technology is oriented on three main directions: communications, information, integration. Information acquisition (collection), processing, integration, and sorting are the basic activities of ITS. In the paper, attempts have been made to present the endeavor that was made to interpret and evaluate the performance of the 27.4 Km long study corridor having eight intersections and four flyovers. The corridor consisting of six lanes as well as eight lanes divided road network. Two categories of data have been collected such as traffic data (traffic volume, spot speed, delay) and road characteristics data (no. of lanes, lane width, bus stops, mid-block sections, intersections, flyovers). The instruments used for collecting the data were video camera, stop watch, radar gun, and mobile GPS (GPS tracker lite). From the analysis, the performance interpretations incorporated were the identification of peak and off-peak hours, congestion and level of service (LOS) at midblock sections and delay followed by plotting the speed contours. The paper proposed the urban corridor management strategies based on sensors integrated into both vehicles and on the roads that those have to be efficiently executable, cost-effective, and familiar to road users. It will be useful to reduce congestion, fuel consumption, and pollution so as to provide comfort, safety, and efficiency to the users.Keywords: ITS strategies, congestion, planning, mobility, safety
Procedia PDF Downloads 1791227 Evaluating the Feasibility of Chemical Dermal Exposure Assessment Model
Authors: P. S. Hsi, Y. F. Wang, Y. F. Ho, P. C. Hung
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The aim of the present study was to explore the dermal exposure assessment model of chemicals that have been developed abroad and to evaluate the feasibility of chemical dermal exposure assessment model for manufacturing industry in Taiwan. We conducted and analyzed six semi-quantitative risk management tools, including UK - Control of substances hazardous to health ( COSHH ) Europe – Risk assessment of occupational dermal exposure ( RISKOFDERM ), Netherlands - Dose related effect assessment model ( DREAM ), Netherlands – Stoffenmanager ( STOFFEN ), Nicaragua-Dermal exposure ranking method ( DERM ) and USA / Canada - Public Health Engineering Department ( PHED ). Five types of manufacturing industry were selected to evaluate. The Monte Carlo simulation was used to analyze the sensitivity of each factor, and the correlation between the assessment results of each semi-quantitative model and the exposure factors used in the model was analyzed to understand the important evaluation indicators of the dermal exposure assessment model. To assess the effectiveness of the semi-quantitative assessment models, this study also conduct quantitative dermal exposure results using prediction model and verify the correlation via Pearson's test. Results show that COSHH was unable to determine the strength of its decision factor because the results evaluated at all industries belong to the same risk level. In the DERM model, it can be found that the transmission process, the exposed area, and the clothing protection factor are all positively correlated. In the STOFFEN model, the fugitive, operation, near-field concentrations, the far-field concentration, and the operating time and frequency have a positive correlation. There is a positive correlation between skin exposure, work relative time, and working environment in the DREAM model. In the RISKOFDERM model, the actual exposure situation and exposure time have a positive correlation. We also found high correlation with the DERM and RISKOFDERM models, with coefficient coefficients of 0.92 and 0.93 (p<0.05), respectively. The STOFFEN and DREAM models have poor correlation, the coefficients are 0.24 and 0.29 (p>0.05), respectively. According to the results, both the DERM and RISKOFDERM models are suitable for performance in these selected manufacturing industries. However, considering the small sample size evaluated in this study, more categories of industries should be evaluated to reduce its uncertainty and enhance its applicability in the future.Keywords: dermal exposure, risk management, quantitative estimation, feasibility evaluation
Procedia PDF Downloads 1701226 Microalgae Hydrothermal Liquefaction Process Optimization and Comprehension to Produce High Quality Biofuel
Authors: Lucie Matricon, Anne Roubaud, Geert Haarlemmer, Christophe Geantet
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Introduction: This case discusses the management of two floor of mouth (FOM) Squamous Cell Carcinomas (SCC) not identified upon initial biopsy. Case Report: A 51 year-old male presented with right FOM erythroleukoplakia. Relevant medical history included alcoholic dependence syndrome and alcoholic liver disease. Relevant drug therapy encompassed acamprosate, folic acid, hydroxocobalamin and thiamine. The patient had a 55.5 pack-year smoking history and alcohol dependence from age 14, drinking 16 units/day. FOM incisional biopsy and histopathological analysis diagnosed Carcinoma in situ. Treatment involved wide local excision. Specimen analysis revealed two separate foci of pT1 moderately differentiated SCCs. Carcinoma staging scans revealed no pathological lymphadenopathy, no local invasion or metastasis. SCCs had been excised in completion with narrow margins. MDT discussion concluded that in view of the field changes it would be difficult to identify specific areas needing further excision, although techniques such as Lugol’s Iodine were considered. Further surgical resection, surgical neck management and sentinel lymph node biopsy was offered. The patient declined intervention, primary management involved close monitoring alongside alcohol and smoking cessation referral. Discussion: Narrow excisional margins can increase carcinoma recurrence risk. Biopsy failed to identify SCCs, despite sampling an area of clinical concern. For gross field change multiple incisional biopsies should be considered to increase chance of accurate diagnosis and appropriate treatment. Coupling of tobacco and alcohol has a synergistic effect, exponentially increasing the relative risk of oral carcinoma development. Tobacco and alcoholic control is fundamental in reducing treatment‑related side effects, recurrence risk, and second primary cancer development.Keywords: microalgae, biofuels, hydrothermal liquefaction, biomass
Procedia PDF Downloads 1341225 Prevalence of Hepatitis B Virus Infection and Its Determinants among Pregnant Women in East Africa: Systematic Review and Meta-Analysis
Authors: Bantie Getnet Yirsaw, Muluken Chanie Agimas, Gebrie Getu Alemu, Tigabu Kidie Tesfie, Nebiyu Mekonnen Derseh, Habtamu Wagnew Abuhay, Meron Asmamaw Alemayehu, Getaneh Awoke Yismaw
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Introduction: Hepatitis B virus (HBV) is one of the major public health problems globally and needs an urgent response. It is one of the most responsible causes of mortality among the five hepatitis viruses, and it affects almost every class of individuals. Thus, the main objective of this study was to determine the pooled prevalence and its determinants among pregnant women in East Africa. Methods: We searched studies using PubMed, Scopus, Embase, ScienceDirect, Google Scholar, and grey literature that were published between January 01/2020 to January 30/2024. The studies were assessed using the Newcastle Ottawa Scale (NOS) quality assessment scale. The random-effect (DerSimonian) model was used to determine the pooled prevalence and associated factors of HBV among pregnant women. Heterogeneity was assessed by I² statistic, sub-group analysis, and sensitivity analysis. Publication bias was assessed by the Egger test, and the analysis was done using STATA version 17. Result: A total of 45 studies with 35639 pregnant women were included in this systematic review and meta-analysis. The overall pooled prevalence of HBV among pregnant women in East Africa was 6.0% (95% CI: 6.0%−7.0%, I² = 89.7%). The highest prevalence of 8% ((95% CI: 6%, 10%), I² = 91.08%) was seen in 2021, and the lowest prevalence of 5% ((95% CI: 4%, 6%) I² = 52.52%) was observed in 2022. A pooled meta-analysis showed that history of surgical procedure (OR = 2.14 (95% CI: 1.27, 3.61)), having multiple sexual partners (OR = 3.87 (95% CI: 2.52, 5.95), history of body tattooing (OR = 2.55 (95% CI: 1.62, 4.01)), history of tooth extraction (OR = 2.09 (95% CI: 1.29, 3.39)), abortion history(OR = 2.20(95% CI: 1.38, 3.50)), history of sharing sharp material (OR = 1.88 (95% CI: 1.07, 3.31)), blood transfusion (OR = 2.41 (95% CI: 1.62, 3.57)), family history of HBV (OR = 4.87 (95% CI: 2.95, 8.05)) and history needle injury (OR = 2.62 (95% CI: 1.20, 5.72)) were significant risk factors associated with HBV infection among pregnant women. Conclusions: The pooled prevalence of HBV infection among pregnant women in East Africa was at an intermediate level and different across countries, ranging from 1.5% to 22.2%. The result of this pooled prevalence was an indication of the need for screening, prevention, and control of HBV infection among pregnant women in the region. Therefore, early identification of risk factors, awareness creation of the mode of transmission of HBV, and implementation of preventive measures are essential in reducing the burden of HBV infection among pregnant women.Keywords: hepatitis B virus, prevalence, determinants, pregnant women, meta-analysis, East Africa
Procedia PDF Downloads 461224 Efficient Reuse of Exome Sequencing Data for Copy Number Variation Callings
Authors: Chen Wang, Jared Evans, Yan Asmann
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With the quick evolvement of next-generation sequencing techniques, whole-exome or exome-panel data have become a cost-effective way for detection of small exonic mutations, but there has been a growing desire to accurately detect copy number variations (CNVs) as well. In order to address this research and clinical needs, we developed a sequencing coverage pattern-based method not only for copy number detections, data integrity checks, CNV calling, and visualization reports. The developed methodologies include complete automation to increase usability, genome content-coverage bias correction, CNV segmentation, data quality reports, and publication quality images. Automatic identification and removal of poor quality outlier samples were made automatically. Multiple experimental batches were routinely detected and further reduced for a clean subset of samples before analysis. Algorithm improvements were also made to improve somatic CNV detection as well as germline CNV detection in trio family. Additionally, a set of utilities was included to facilitate users for producing CNV plots in focused genes of interest. We demonstrate the somatic CNV enhancements by accurately detecting CNVs in whole exome-wide data from the cancer genome atlas cancer samples and a lymphoma case study with paired tumor and normal samples. We also showed our efficient reuses of existing exome sequencing data, for improved germline CNV calling in a family of the trio from the phase-III study of 1000 Genome to detect CNVs with various modes of inheritance. The performance of the developed method is evaluated by comparing CNV calling results with results from other orthogonal copy number platforms. Through our case studies, reuses of exome sequencing data for calling CNVs have several noticeable functionalities, including a better quality control for exome sequencing data, improved joint analysis with single nucleotide variant calls, and novel genomic discovery of under-utilized existing whole exome and custom exome panel data.Keywords: bioinformatics, computational genetics, copy number variations, data reuse, exome sequencing, next generation sequencing
Procedia PDF Downloads 2581223 Laboratory Diagnostic Testing of Peste des Petits Ruminants in Georgia
Authors: Nino G. Vepkhvadze, Tea Enukidze
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Every year the number of countries around the world face the risk of the spread of infectious diseases that bring significant ecological and social-economic damage. Hence, the importance of food product safety is emphasized that is the issue of interest for many countries. To solve them, it’s necessary to conduct preventive measures against the diseases, have accurate diagnostic results, leadership, and management. The Peste des petits ruminants (PPR) disease is caused by a morbillivirus closely related to the rinderpest virus. PPR is a transboundary disease as it emerges and evolves, considered as one of the top most damaging animal diseases. The disease imposed a serious threat to sheep-breeding when the farms of sheep, goats are significantly growing within the country. In January 2016, PPR was detected in Georgia. Up to present the origin of the virus, the age relationship of affected ruminants and the distribution of PPRV in Georgia remains unclear. Due to the nature of PPR, and breeding practices in the country, reemerging of the disease in Georgia is highly likely. The purpose of the studies is to provide laboratories with efficient tools allowing the early detection of PPR emergence and re-emergences. This study is being accomplished under the Biological Threat Reduction Program project with the support of the Defense Threat Reduction Agency (DTRA). The purpose of the studies is to investigate the samples and identify areas at high risk of the disease. Georgia has a high density of small ruminant herds bred as free-ranging, close to international borders. Kakheti region, Eastern Georgia, will be considered as area of high priority for PPR surveillance. For this reason, in 2019, in Kakheti region investigated n=484 sheep and goat serum and blood samples from the same animals, utilized serology and molecular biology methods. All samples were negative by RT-PCR, and n=6 sheep samples were seropositive by ELISA-Ab. Future efforts will be concentrated in areas where the risk of PPR might be high such as international bordering regions of Georgia. For diagnostics, it is important to integrate the PPRV knowledge with epidemiological data. Based on these diagnostics, the relevant agencies will be able to control the disease surveillance.Keywords: animal disease, especially dangerous pathogen, laboratory diagnostics, virus
Procedia PDF Downloads 1171222 Clinical Risk Score for Mortality and Predictors of Severe Disease in Adult Patients with Dengue
Authors: Siddharth Jain, Abhenil Mittal, Surendra Kumar Sharma
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Background: With its recent emergence and re-emergence, dengue has become a major international public health concern, imposing significant financial burden especially in developing countries. Despite aggressive control measures in place, India experienced one of its largest outbreaks in 2015 with Delhi being most severely affected. There is a lack of reliable predictors of disease severity and mortality in dengue. The present study was carried out to identify these predictors during the 2015 outbreak. Methods: This prospective observational study conducted at an apex tertiary care center in Delhi, India included confirmed adult dengue patients admitted between August-November 2015. Patient demographics, clinical details, and laboratory findings were recorded in a predesigned proforma. Appropriate statistical tests were used to summarize and compare the clinical and laboratory characteristics and derive predictors of mortality and severe disease, while developing a clinical risk score for mortality. Serotype analysis was also done for 75 representative samples to identify the dominant serotypes. Results: Data of 369 patients were analyzed (mean age 30.9 years; 67% males). Of these, 198 (54%) patients had dengue fever, 125 (34%) had dengue hemorrhagic fever (DHF Grade 1,2)and 46 (12%) developed dengue shock syndrome (DSS). Twenty two (6%) patients died. Late presentation to the hospital (≥5 days after onset) and dyspnoea at rest were identified as independent predictors of severe disease. Age ≥ 24 years, dyspnoea at rest and altered sensorium were identified as independent predictors of mortality. A clinical risk score was developed (12*age + 14*sensorium + 10*dyspnoea) which, if ≥ 22, predicted mortality with a high sensitivity (81.8%) and specificity (79.2%). The predominant serotypes in Delhi (2015) were DENV-2 and DENV-4. Conclusion: Age ≥ 24 years, dyspnoea at rest and altered sensorium were identified as independent predictors of mortality. Platelet counts did not determine the outcome in dengue patients. Timely referral/access to health care is important. Development and use of validated predictors of disease severity and simple clinical risk scores, which can be applied in all healthcare settings, can help minimize mortality and morbidity, especially in resource limited settings.Keywords: dengue, mortality, predictors, severity
Procedia PDF Downloads 3091221 Development and Evaluation of a Calcium Rich Plant-Based Supplement on Bone Turnover of Peri and Post Menopausal Women
Authors: Gayathri.G, Hemamalini.A.J, Chandrasekaran.A
Abstract:
Problem statement: Nutritional deficiency, especially calcium, may lead to poor bone formation and mineralization. Although there are plenty of synthetic supplements available, it is essential to make a calcium rich food supplement accessible to combat calcium deficiency that could be readily prepared at the household level. Thus the current study aimed to formulate and standardize an indigenous low-cost calcium-rich food supplement and to study the impact of supplementation on the bone resorption and formation markers. Methods: A Randomized controlled trial was conducted with 60 subjects distributed equally in control and experimental groups, including perimenopausal and postmenopausal women. A plant-based calcium-rich product was developed and supplemented in form of balls as a midmorning and evening snack by addition of optimized proportions of leaves of Sesbania Grandiflora, seeds of Sesamum indicum, Eleusine coracana, Glycine max, Vigna mungo for a period of 6 months. Postmenopausal and perimenopausal women received 1200mg and 800mg of calcium per day from the supplemented, respectively. Outcome measures like serum calcium; betacrosslaps (bone resorption marker) and total P1NP (bone absorption marker) were assessed after 3 months and after 6 months. Results: There were no significant changes seen in the serum calcium and total P1NP levels (bone formation marker) among the subjects during the supplementation period. The bone resorption marker (betacrosslaps) reduced in all the groups and the reduction (0.32 ± 0.130 ng/ml to 0.25 ± 0.130 ng/ml) was found to be statistically highly significant (p < 0.01) in experimental group of perimenopausal subjects and significant (p < 0.05) in experimental group of postmenopausal subjects (1.11 ± 0.290 ng/ml to 0.42 ± 0.263 ng/ml). Conclusion: With the current severe calcium deficiency in the Indian population, integrating low-cost, calcium-rich native foods that could be readily prepared at household level would be useful in raising the nutritional consumption of calcium, which would, in turn, decrease bone turnover.Keywords: calcium, sesbania grandiflora, sesamum indicum, eleusine coracana, glycine max, vigna mungo, postmenopause, perimenopause, bone resorption, bone absorption, betacrosslaps, total P1NP
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