Search results for: single electrode measurement
75 Industrial Production of the Saudi Future Dwelling: A Saudi Volumetric Solution for Single Family Homes, Leveraging Industry 4.0 with Scalable Automation, Hybrid Structural Insulated Panels Technology and Local Materials
Authors: Bandar Alkahlan
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The King Abdulaziz City for Science and Technology (KACST) created the Saudi Future Dwelling (SFD) initiative to identify, localize and commercialize a scalable home manufacturing technology suited to deployment across the Kingdom of Saudi Arabia (KSA). This paper outlines the journey, the creation of the international project delivery team, the product design, the selection of the process technologies, and the outcomes. A target was set to remove 85% of the construction and finishing processes from the building site as these activities could be more efficiently completed in a factory environment. Therefore, integral to the SFD initiative is the successful industrialization of the home building process using appropriate technologies, automation, robotics, and manufacturing logistics. The technologies proposed for the SFD housing system are designed to be energy efficient, economical, fit for purpose from a Saudi cultural perspective, and will minimize the use of concrete, relying mainly on locally available Saudi natural materials derived from the local resource industries. To this end, the building structure is comprised of a hybrid system of structural insulated panels (SIP), combined with a light gauge steel framework manufactured in a large format panel system. The paper traces the investigative process and steps completed by the project team during the selection process. As part of the SFD Project, a pathway was mapped out to include a proof-of-concept prototype housing module and the set-up and commissioning of a lab-factory complete with all production machinery and equipment necessary to simulate a full-scale production environment. The prototype housing module was used to validate and inform current and future product design as well as manufacturing process decisions. A description of the prototype design and manufacture is outlined along with valuable learning derived from the build and how these results were used to enhance the SFD project. The industrial engineering concepts and lab-factory detailed design and layout are described in the paper, along with the shop floor I.T. management strategy. Special attention was paid to showcase all technologies within the lab-factory as part of the engagement strategy with private investors to leverage the SFD project with large scale factories throughout the Kingdom. A detailed analysis is included in the process surrounding the design, specification, and procurement of the manufacturing machinery, equipment, and logistical manipulators required to produce the SFD housing modules. The manufacturing machinery was comprised of a combination of standardized and bespoke equipment from a wide range of international suppliers. The paper describes the selection process, pre-ordering trials and studies, and, in some cases, the requirement for additional research and development by the equipment suppliers in order to achieve the SFD objectives. A set of conclusions is drawn describing the results achieved thus far, along with a list of recommended ongoing operational tests, enhancements, research, and development aimed at achieving full-scale engagement with private sector investment and roll-out of the SFD project across the Kingdom.Keywords: automation, dwelling, manufacturing, product design
Procedia PDF Downloads 12174 Microplastic Concentrations and Fluxes in Urban Compartments: A Systemic Approach at the Scale of the Paris Megacity
Authors: Rachid Dris, Robin Treilles, Max Beaurepaire, Minh Trang Nguyen, Sam Azimi, Vincent Rocher, Johnny Gasperi, Bruno Tassin
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Microplastic sources and fluxes in urban catchments are only poorly studied. Most often, the approaches taken focus on a single source and only carry out a description of the contamination levels and type (shape, size, polymers). In order to gain an improved knowledge of microplastic inputs at urban scales, estimating and comparing various fluxes is necessary. The Laboratoire Eau, Environnement et Systèmes Urbains (LEESU), the Laboratoire Eau Environnement (LEE) and the SIAAP (Service public de l’assainissement francilien) initiated several projects to investigate different urban sources and flows of microplastics. A systemic approach is undertaken at the scale of Paris Megacity, and several compartments are considered, including atmospheric fallout, wastewater treatments plants, runoff and combined sewer overflows. These investigations are carried out within the Limnoplast and OPUR projects. Atmospheric fallout was sampled during consecutive periods ranging from 2 to 3 weeks with a stainless-steel funnel. Both wet and dry periods were considered. Different treatment steps were sampled in 2 wastewater treatment plants (Seine-Amont for activated sludge and Seine-Centre for biofiltration) of the SIAAP, including sludge samples. Microplastics were also investigated in combined sewer overflows as well as in stormwater at the outlet suburban catchment (Sucy-en-Brie, France) during four rain events. Samples are treated using hydroperoxide digestion (H₂O₂ 30 %) in order to reduce organic material. Microplastics are then extracted from the samples with a density separation step using NaI (d=1.6 g.cm⁻³). Samples are filtered on metallic filters with a porosity of 14 µm between steps to separate them from the solutions (H₂O₂ and NaI). The last filtration was carried out on alumina filters. Infrared mapping analysis (using a micro-FTIR with an MCT detector) is performed on each alumina filter. The resulting maps are analyzed using a microplastic analysis software simple, developed by Aalborg University, Denmark and Alfred Wegener Institute, Germany. Blanks were systematically carried out to consider sample contamination. This presentation aims at synthesizing the data found in the various projects. In order to carry out a systemic approach and compare the various inputs, all the data were converted into annual microplastic fluxes (number of microplastics per year), and extrapolated to the Parisian agglomeration. PP, PE and alkyd are the most prevalent polymers found in storm water samples. Rain intensity and microplastic concentrations did not show any clear correlation. Considering the runoff volumes and the impervious surface area of the studied catchment, a flux of 4*107–9*107 MPs.yr⁻¹.ha⁻¹ was estimated. Samples of wastewater treatment plants and atmospheric fallout are currently being analyzed in order to finalize this assessment. The representativeness of such samplings and uncertainties related to the extrapolations will be discussed and gaps in knowledge will be identified. The data provided by such an approach will help to prioritize future research as well as policy efforts.Keywords: microplastics, atmosphere, wastewater, urban runoff, Paris megacity, urban waters
Procedia PDF Downloads 18073 The Effects of the Interaction between Prenatal Stress and Diet on Maternal Insulin Resistance and Inflammatory Profile
Authors: Karen L. Lindsay, Sonja Entringer, Claudia Buss, Pathik D. Wadhwa
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Maternal nutrition and stress are independently recognized as among the most important factors that influence prenatal biology, with implications for fetal development and poor pregnancy outcomes. While there is substantial evidence from non-pregnancy human and animal studies that a complex, bi-directional relationship exists between nutrition and stress, to the author’s best knowledge, their interaction in the context of pregnancy has been significantly understudied. The aim of this study is to assess the interaction between maternal psychological stress and diet quality across pregnancy and its effects on biomarkers of prenatal insulin resistance and inflammation. This is a prospective longitudinal study of N=235 women carrying a healthy, singleton pregnancy, recruited from prenatal clinics of the University of California, Irvine Medical Center. Participants completed a 4-day ambulatory assessment in early, middle and late pregnancy, which included multiple daily electronic diary entries using Ecological Momentary Assessment (EMA) technology on a dedicated study smartphone. The EMA diaries gathered moment-level data on maternal perceived stress, negative mood, positive mood and quality of social interactions. The numerical scores for these variables were averaged across each study time-point and converted to Z-scores. A single composite variable for 'STRESS' was computed as follows: (Negative mood+Perceived stress)–(Positive mood+Social interaction quality). Dietary intakes were assessed by three 24-hour dietary recalls conducted within two weeks of each 4-day assessment. Daily nutrient and food group intakes were averaged across each study time-point. The Alternative Healthy Eating Index adapted for pregnancy (AHEI-P) was computed for early, middle and late pregnancy as a validated summary measure of diet quality. At the end of each 4-day ambulatory assessment, women provided a fasting blood sample, which was assayed for levels of glucose, insulin, Interleukin (IL)-6 and Tumor Necrosis Factor (TNF)-α. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was computed. Pearson’s correlation was used to explore the relationship between maternal STRESS and AHEI-P within and between each study time-point. Linear regression was employed to test the association of the stress-diet interaction (STRESS*AHEI-P) with the biological markers HOMA-IR, IL-6 and TNF-α at each study time-point, adjusting for key covariates (pre-pregnancy body mass index, maternal education level, race/ethnicity). Maternal STRESS and AHEI-P were significantly inversely correlated in early (r=-0.164, p=0.018) and mid-pregnancy (-0.160, p=0.019), and AHEI-P from earlier gestational time-points correlated with later STRESS (early AHEI-P x mid STRESS: r=-0.168, p=0.017; mid AHEI-P x late STRESS: r=-0.142, p=0.041). In regression models, the interaction term was not associated with HOMA-IR or IL-6 at any gestational time-point. The stress-diet interaction term was significantly associated with TNF-α according to the following patterns: early AHEI-P*early STRESS vs early TNF-α (p=0.005); early AHEI-P*early STRESS vs mid TNF-α (p=0.002); early AHEI-P*mid STRESS vs mid TNF-α (p=0.005); mid AHEI-P*mid STRESS vs mid TNF-α (p=0.070); mid AHEI-P*late STRESS vs late TNF-α (p=0.011). Poor diet quality is significantly related to higher psychosocial stress levels in pregnant women across gestation, which may promote inflammation via TNF-α. Future prenatal studies should consider the combined effects of maternal stress and diet when evaluating either one of these factors on pregnancy or infant outcomes.Keywords: diet quality, inflammation, insulin resistance, nutrition, pregnancy, stress, tumor necrosis factor-alpha
Procedia PDF Downloads 20072 Utilization of Informatics to Transform Clinical Data into a Simplified Reporting System to Examine the Analgesic Prescribing Practices of a Single Urban Hospital’s Emergency Department
Authors: Rubaiat S. Ahmed, Jemer Garrido, Sergey M. Motov
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Clinical informatics (CI) enables the transformation of data into a systematic organization that improves the quality of care and the generation of positive health outcomes.Innovative technology through informatics that compiles accurate data on analgesic utilization in the emergency department can enhance pain management in this important clinical setting. We aim to establish a simplified reporting system through CI to examine and assess the analgesic prescribing practices in the EDthrough executing a U.S. federal grant project on opioid reduction initiatives. Queried data points of interest from a level-one trauma ED’s electronic medical records were used to create data sets and develop informational/visual reporting dashboards (on Microsoft Excel and Google Sheets) concerning analgesic usage across several pre-defined parameters and performance metrics using CI. The data was then qualitatively analyzed to evaluate ED analgesic prescribing trends by departmental clinicians and leadership. During a 12-month reporting period (Dec. 1, 2020 – Nov. 30, 2021) for the ongoing project, about 41% of all ED patient visits (N = 91,747) were for pain conditions, of which 81.6% received analgesics in the ED and at discharge (D/C). Of those treated with analgesics, 24.3% received opioids compared to 75.7% receiving opioid alternatives in the ED and at D/C, including non-pharmacological modalities. Demographics showed among patients receiving analgesics, 56.7% were aged between 18-64, 51.8% were male, 51.7% were white, and 66.2% had government funded health insurance. Ninety-one percent of all opioids prescribed were in the ED, with intravenous (IV) morphine, IV fentanyl, and morphine sulfate immediate release (MSIR) tablets accounting for 88.0% of ED dispensed opioids. With 9.3% of all opioids prescribed at D/C, MSIR was dispensed 72.1% of the time. Hydrocodone, oxycodone, and tramadol usage to only 10-15% of the time, and hydromorphone at 0%. Of opioid alternatives, non-steroidal anti-inflammatory drugs were utilized 60.3% of the time, 23.5% with local anesthetics and ultrasound-guided nerve blocks, and 7.9% with acetaminophen as the primary non-opioid drug categories prescribed by ED providers. Non-pharmacological analgesia included virtual reality and other modalities. An average of 18.5 ED opioid orders and 1.9 opioid D/C prescriptions per 102.4 daily ED patient visits was observed for the period. Compared to other specialties within our institution, 2.0% of opioid D/C prescriptions are given by ED providers, compared to the national average of 4.8%. Opioid alternatives accounted for 69.7% and 30.3% usage, versus 90.7% and 9.3% for opioids in the ED and D/C, respectively.There is a pressing need for concise, relevant, and reliable clinical data on analgesic utilization for ED providers and leadership to evaluate prescribing practices and make data-driven decisions. Basic computer software can be used to create effective visual reporting dashboards with indicators that convey relevant and timely information in an easy-to-digest manner. We accurately examined our ED's analgesic prescribing practices using CI through dashboard reporting. Such reporting tools can quickly identify key performance indicators and prioritize data to enhance pain management and promote safe prescribing practices in the emergency setting.Keywords: clinical informatics, dashboards, emergency department, health informatics, healthcare informatics, medical informatics, opioids, pain management, technology
Procedia PDF Downloads 14471 Geographic Information System Based Multi-Criteria Subsea Pipeline Route Optimisation
Authors: James Brown, Stella Kortekaas, Ian Finnie, George Zhang, Christine Devine, Neil Healy
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The use of GIS as an analysis tool for engineering decision making is now best practice in the offshore industry. GIS enables multidisciplinary data integration, analysis and visualisation which allows the presentation of large and intricate datasets in a simple map-interface accessible to all project stakeholders. Presenting integrated geoscience and geotechnical data in GIS enables decision makers to be well-informed. This paper is a successful case study of how GIS spatial analysis techniques were applied to help select the most favourable pipeline route. Routing a pipeline through any natural environment has numerous obstacles, whether they be topographical, geological, engineering or financial. Where the pipeline is subjected to external hydrostatic water pressure and is carrying pressurised hydrocarbons, the requirement to safely route the pipeline through hazardous terrain becomes absolutely paramount. This study illustrates how the application of modern, GIS-based pipeline routing techniques enabled the identification of a single most-favourable pipeline route crossing of a challenging seabed terrain. Conventional approaches to pipeline route determination focus on manual avoidance of primary constraints whilst endeavouring to minimise route length. Such an approach is qualitative, subjective and is liable to bias towards the discipline and expertise that is involved in the routing process. For very short routes traversing benign seabed topography in shallow water this approach may be sufficient, but for deepwater geohazardous sites, the need for an automated, multi-criteria, and quantitative approach is essential. This study combined multiple routing constraints using modern least-cost-routing algorithms deployed in GIS, hitherto unachievable with conventional approaches. The least-cost-routing procedure begins with the assignment of geocost across the study area. Geocost is defined as a numerical penalty score representing hazard posed by each routing constraint (e.g. slope angle, rugosity, vulnerability to debris flows) to the pipeline. All geocosted routing constraints are combined to generate a composite geocost map that is used to compute the least geocost route between two defined terminals. The analyses were applied to select the most favourable pipeline route for a potential gas development in deep water. The study area is geologically complex with a series of incised, potentially active, canyons carved into a steep escarpment, with evidence of extensive debris flows. A similar debris flow in the future could cause significant damage to a poorly-placed pipeline. Protruding inter-canyon spurs offer lower-gradient options for ascending an escarpment but the vulnerability of periodic failure of these spurs is not well understood. Close collaboration between geoscientists, pipeline engineers, geotechnical engineers and of course the gas export pipeline operator guided the analyses and assignment of geocosts. Shorter route length, less severe slope angles, and geohazard avoidance were the primary drivers in identifying the most favourable route.Keywords: geocost, geohazard, pipeline route determination, pipeline route optimisation, spatial analysis
Procedia PDF Downloads 40670 Angiopermissive Foamed and Fibrillar Scaffolds for Vascular Graft Applications
Authors: Deon Bezuidenhout
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Pre-seeding with autologous endothelial cells improves the long-term patency of synthetic vascular grafts levels obtained with autografts, but is limited to a single centre due to resource, time and other constraints. Spontaneous in vivo endothelialization would obviate the need for pre-seeding, but has been shown to be absent in man due to limited transanastomotic and fallout healing, and the lack of transmural ingrowth due to insufficient porosity. Two types of graft scaffolds with increased interconnected porosity for improved tissue ingrowth and healing are thus proposed and described. Foam-type polyurethane (PU) scaffolds with small, medium and large, interconnected pores were made by phase inversion and spherical porogen extraction, with and without additional surface modification with covalently attached heparin and subsequent loading with and delivery of growth factors. Fibrillar scaffolds were made either by standard electrospinning using degradable PU (Degrapol®), or by dual electrospinning using non-degradable PU. The latter process involves sacrificial fibres that are co-spun with structural fibres and subsequently removed to increased porosity and pore size. Degrapol samples were subjected to in vitro degradation, and all scaffold types were evaluated in vivo for tissue ingrowth and vascularization using rat subcutaneous model. The foam scaffolds were additionally evaluated in a circulatory (rat infrarenal aortic interposition) model that allows for the grafts to be anastomotically and/or ablumenally isolated to discern and determine endothelialization mode. Foam-type grafts with large (150 µm) pores showed improved subcutaneous healing in terms of vascularization and inflammatory response over smaller pore sizes (60 and 90µm), and vascularization of the large porosity scaffolds was significantly increased by more than 70% by heparin modification alone, and by 150% to 400% when combined with growth factors. In the circulatory model, extensive transmural endothelialization (95±10% at 12 w) was achieved. Fallout healing was shown to be sporadic and limited in groups that were ablumenally isolated to prevent transmural ingrowth (16±30% wrapped vs. 80±20% control; p<0.002). Heparinization and GF delivery improved both mural vascularization and lumenal endothelialization. Degrapol electrospun scaffolds showed decrease in molecular mass and corresponding tensile strength over the first 2 weeks, but very little decrease in mass over the 4w test period. Studies on the effect of tissue ingrowth with and without concomitant degradation of the scaffolds, are being used to develop material models for the finite element modelling. In the case of the dual-spun scaffolds, the PU fibre fraction could be controlled shown to vary linearly with porosity (P = −0.18FF +93.5, r2=0.91), which in turn showed inverse linear correlation with tensile strength and elastic modulus (r2 > 0.96). Calculated compliance and burst pressures of the scaffolds increased with fibre fraction, and compliances matching the human popliteal artery (5-10 %/100 mmHg), and high burst pressures (> 2000 mmHg) could be achieved. Increasing porosity (76 to 82 and 90%) resulted in increased tissue ingrowth from 33±7 to 77±20 and 98±1% after 28d. Transmural endothelialization of highly porous foamed grafts is achievable in a circulatory model, and the enhancement of porosity and tissue ingrowth may hold the key the development of spontaneously endothelializing electrospun grafts.Keywords: electrospinning, endothelialization, porosity, scaffold, vascular graft
Procedia PDF Downloads 29669 Gene Expression Meta-Analysis of Potential Shared and Unique Pathways Between Autoimmune Diseases Under anti-TNFα Therapy
Authors: Charalabos Antonatos, Mariza Panoutsopoulou, Georgios K. Georgakilas, Evangelos Evangelou, Yiannis Vasilopoulos
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The extended tissue damage and severe clinical outcomes of autoimmune diseases, accompanied by the high annual costs to the overall health care system, highlight the need for an efficient therapy. Increasing knowledge over the pathophysiology of specific chronic inflammatory diseases, namely Psoriasis (PsO), Inflammatory Bowel Diseases (IBD) consisting of Crohn’s disease (CD) and Ulcerative colitis (UC), and Rheumatoid Arthritis (RA), has provided insights into the underlying mechanisms that lead to the maintenance of the inflammation, such as Tumor Necrosis Factor alpha (TNF-α). Hence, the anti-TNFα biological agents pose as an ideal therapeutic approach. Despite the efficacy of anti-TNFα agents, several clinical trials have shown that 20-40% of patients do not respond to treatment. Nowadays, high-throughput technologies have been recruited in order to elucidate the complex interactions in multifactorial phenotypes, with the most ubiquitous ones referring to transcriptome quantification analyses. In this context, a random effects meta-analysis of available gene expression cDNA microarray datasets was performed between responders and non-responders to anti-TNFα therapy in patients with IBD, PsO, and RA. Publicly available datasets were systematically searched from inception to 10th of November 2020 and selected for further analysis if they assessed the response to anti-TNFα therapy with clinical score indexes from inflamed biopsies. Specifically, 4 IBD (79 responders/72 non-responders), 3 PsO (40 responders/11 non-responders) and 2 RA (16 responders/6 non-responders) datasetswere selected. After the separate pre-processing of each dataset, 4 separate meta-analyses were conducted; three disease-specific and a single combined meta-analysis on the disease-specific results. The MetaVolcano R package (v.1.8.0) was utilized for a random-effects meta-analysis through theRestricted Maximum Likelihood (RELM) method. The top 1% of the most consistently perturbed genes in the included datasets was highlighted through the TopConfects approach while maintaining a 5% False Discovery Rate (FDR). Genes were considered as Differentialy Expressed (DEGs) as those with P ≤ 0.05, |log2(FC)| ≥ log2(1.25) and perturbed in at least 75% of the included datasets. Over-representation analysis was performed using Gene Ontology and Reactome Pathways for both up- and down-regulated genes in all 4 performed meta-analyses. Protein-Protein interaction networks were also incorporated in the subsequentanalyses with STRING v11.5 and Cytoscape v3.9. Disease-specific meta-analyses detected multiple distinct pro-inflammatory and immune-related down-regulated genes for each disease, such asNFKBIA, IL36, and IRAK1, respectively. Pathway analyses revealed unique and shared pathways between each disease, such as Neutrophil Degranulation and Signaling by Interleukins. The combined meta-analysis unveiled 436 DEGs, 86 out of which were up- and 350 down-regulated, confirming the aforementioned shared pathways and genes, as well as uncovering genes that participate in anti-inflammatory pathways, namely IL-10 signaling. The identification of key biological pathways and regulatory elements is imperative for the accurate prediction of the patient’s response to biological drugs. Meta-analysis of such gene expression data could aid the challenging approach to unravel the complex interactions implicated in the response to anti-TNFα therapy in patients with PsO, IBD, and RA, as well as distinguish gene clusters and pathways that are altered through this heterogeneous phenotype.Keywords: anti-TNFα, autoimmune, meta-analysis, microarrays
Procedia PDF Downloads 18168 Surface Plasmon Resonance Imaging-Based Epigenetic Assay for Blood DNA Post-Traumatic Stress Disorder Biomarkers
Authors: Judy M. Obliosca, Olivia Vest, Sandra Poulos, Kelsi Smith, Tammy Ferguson, Abigail Powers Lott, Alicia K. Smith, Yang Xu, Christopher K. Tison
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Post-Traumatic Stress Disorder (PTSD) is a mental health problem that people may develop after experiencing traumatic events such as combat, natural disasters, and major emotional challenges. Tragically, the number of military personnel with PTSD correlates directly with the number of veterans who attempt suicide, with the highest rate in the Army. Research has shown epigenetic risks in those who are prone to several psychiatric dysfunctions, particularly PTSD. Once initiated in response to trauma, epigenetic alterations in particular, the DNA methylation in the form of 5-methylcytosine (5mC) alters chromatin structure and represses gene expression. Current methods to detect DNA methylation, such as bisulfite-based genomic sequencing techniques, are laborious and have massive analysis workflow while still having high error rates. A faster and simpler detection method of high sensitivity and precision would be useful in a clinical setting to confirm potential PTSD etiologies, prevent other psychiatric disorders, and improve military health. A nano-enhanced Surface Plasmon Resonance imaging (SPRi)-based assay that simultaneously detects site-specific 5mC base (termed as PTSD base) in methylated genes related to PTSD is being developed. The arrays on a sensing chip were first constructed for parallel detection of PTSD bases using synthetic and genomic DNA (gDNA) samples. For the gDNA sample extracted from the whole blood of a PTSD patient, the sample was first digested using specific restriction enzymes, and fragments were denatured to obtain single-stranded methylated target genes (ssDNA). The resulting mixture of ssDNA was then injected into the assay platform, where targets were captured by specific DNA aptamer probes previously immobilized on the surface of a sensing chip. The PTSD bases in targets were detected by anti-5-methylcytosine antibody (anti-5mC), and the resulting signals were then enhanced by the universal nanoenhancer. Preliminary results showed successful detection of a PTSD base in a gDNA sample. Brighter spot images and higher delta values (control-subtracted reflectivity signal) relative to those of the control were observed. We also implemented the in-house surface activation system for detection and developed SPRi disposable chips. Multiplexed PTSD base detection of target methylated genes in blood DNA from PTSD patients of severity conditions (asymptomatic and severe) was conducted. This diagnostic capability being developed is a platform technology, and upon successful implementation for PTSD, it could be reconfigured for the study of a wide variety of neurological disorders such as traumatic brain injury, Alzheimer’s disease, schizophrenia, and Huntington's disease and can be extended to the analyses of other sample matrices such as urine and saliva.Keywords: epigenetic assay, DNA methylation, PTSD, whole blood, multiplexing
Procedia PDF Downloads 12467 Living in the Edge: Crisis in Indian Tea Industry and Social Deprivation of Tea Garden Workers in Dooars Region of India
Authors: Saraswati Kerketta
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Tea industry is one of the oldest organised sector of India. It employs roughly 1.5 million people directly. Since the last decade Indian tea industry, especially in the northern region is experiencing worst crisis in the post-independence period. Due to many reason the prices of tea show steady decline. The workers are paid one of the lowest wage in tea industry in the world (1.5$ a day) below the UN's $2 a day for extreme poverty. The workers rely on addition benefits from plantation which includes food, housing and medical facilities. These have been effective means of enslavement of generations of labourers by the owners. There is hardly any change in the tea estates where the owners determine the fate of workers. When the tea garden is abandoned or is closed all the facilities disappear immediately. The workers are the descendants of tribes from central India also known as 'tea tribes'. Alienated from their native place, the geographical and social isolation compounded their vulnerability of these people. The economy of the region being totally dependent on tea has resulted in absolute unemployment for the workers of these tea gardens. With no other livelihood and no land to grow food, thousands of workers faced hunger and starvation. The Plantation Labour Act which ensures the decent working and living condition is violated continuously. The labours are forced to migrate and are also exposed to the risk of human trafficking. Those who are left behind suffers from starvation, malnutrition and disease. The condition in the sick tea plantation is no better. Wage are not paid regularly, subsidised food, fuel are also not supplied properly. Health care facilities are in very bad shape. Objectives: • To study the socio-cultural and demographic characteristics of the tea garden labourers in the study area. • To examine the social situation of workers in sick estates in dooars region. • To assess the magnitude of deprivation the impact of economic crisis on abandoned and closed tea estates in the region. Data Base: The study is based on data collected from field survey. Methods: Quantative: Cross-Tabulation, Regression analysis. Qualitative: Household Survey, Focussed Group Discussion, In-depth interview of key informants. Findings: Purchasing power parity has declined since in last three decades. There has been many fold increase in migration. Males migrates long distance towards central and west and south India. Females and children migrates both long and short distance. No one has reported to migrate back to the place of origin of their ancestors. Migrant males work mostly as construction labourers and as factory workers whereas females and children work as domestic help and construction labourers. In about 37 cases either they haven't contacted their families in last six months or are not traceable. The families with single earning members are more likely to migrate. Burden of disease and the duration of sickness, abandonment and closure of plantation are closely related. Death tolls are likely to rise 1.5 times in sick tea gardens and three times in closed tea estates. Sixty percent of the people are malnourished in the sick tea gardens and more than eighty five per cent in abandoned and sick tea gardens.Keywords: migration, trafficking, starvation death, tea garden workers
Procedia PDF Downloads 38366 Poverty Reduction in European Cities: Local Governments’ Strategies and Programmes to Reduce Poverty; Interview Results from Austria
Authors: Melanie Schinnerl, Dorothea Greiling
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In the context of the 2020 strategy, poverty and its fight returned to the center of national political efforts. This served as motivation for an Austrian research grant-funded project to focus on the under-researched local government level with the aim to identify municipal best-practice cases and to derive policy implications for Austria. Designing effective poverty reduction strategies is a complex challenge which calls for an integrated multi-actor in approach. Cities are increasingly confronted to combat poverty, even in rich EU-member states. By doing so cities face substantial demographic, cultural, economic and social challenges as well as changing welfare state regimes. Furthermore, there is a low willingness of (right-wing) governments to support the poor. Against this background, the research questions are: 1. How do local governments define poverty? 2. Who are the main risk groups and what are the most pressing problems when fighting urban poverty? 3. What is regarded as successful anti-poverty initiatives? 4. What is the underlying welfare state concept? To address the research questions a multi-method approach was chosen, consisting of a systematic literature analysis, a comprehensive document analysis, and expert interviews. For interpreting the data the project follows the qualitative-interpretive paradigm. Municipal approaches for reducing poverty are compared based on deductive, as well as inductive identified criteria. In addition to an intensive literature analysis, interviews (40) were conducted in Austria since the project started in March 2018. From the other countries, 14 responses have been collected, providing a first insight. Regarding the definition of poverty the EU SILC-definition as well as counting the persons who receive need-based minimum social benefits, the Austrian form of social welfare, are the predominant approaches in Austria. In addition to homeless people, single-parent families, un-skilled persons, long-term unemployed persons, migrants (first and second generation), refugees and families with at least 3 children were frequently mentioned. The most pressing challenges for Austrian cities are: expected reductions of social budgets, a great insecurity of the central government's social policy reform plans, the growing number of homeless people and a lack of affordable housing. Together with affordable housing, old-age poverty will gain more importance in the future. The Austrian best practice examples, suggested by interviewees, focused primarily on homeless, children and young people (till 25). Central government’s policy changes have already negative effects on programs for refugees and elderly unemployed. Social Housing in Vienna was frequently mentioned as an international best practice case, other growing cities can learn from. The results from Austria indicate a change towards the social investment state, which primarily focuses on children and labour market integration. The first insights from the other countries indicate that affordable housing and labor market integration are cross-cutting issues. Inherited poverty and old-age poverty seems to be more pressing outside Austria.Keywords: anti-poverty policies, European cities, empirical study, social investment
Procedia PDF Downloads 11765 Monte Carlo Risk Analysis of a Carbon Abatement Technology
Authors: Hameed Rukayat Opeyemi, Pericles Pilidis, Pagone Emanuele
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Climate change represents one of the single most challenging problems facing the world today. According to the National Oceanic and Administrative Association, Atmospheric temperature rose almost 25% since 1958, Artic sea ice has shrunk 40% since 1959 and global sea levels have risen more than 5.5 cm since 1990. Power plants are the major culprits of GHG emission to the atmosphere. Several technologies have been proposed to reduce the amount of GHG emitted to the atmosphere from power plant, one of which is the less researched Advanced zero emission power plant. The advanced zero emission power plants make use of mixed conductive membrane (MCM) reactor also known as oxygen transfer membrane (OTM) for oxygen transfer. The MCM employs membrane separation process. The membrane separation process was first introduced in 1899 when Walter Hermann Nernst investigated electric current between metals and solutions. He found that when a dense ceramic is heated, current of oxygen molecules move through it. In the bid to curb the amount of GHG emitted to the atmosphere, the membrane separation process was applied to the field of power engineering in the low carbon cycle known as the Advanced zero emission power plant (AZEP cycle). The AZEP cycle was originally invented by Norsk Hydro, Norway and ABB Alstom power (now known as Demag Delaval Industrial turbo machinery AB), Sweden. The AZEP drew a lot of attention because its ability to capture ~100% CO2 and also boasts of about 30-50 % cost reduction compared to other carbon abatement technologies, the penalty in efficiency is also not as much as its counterparts and crowns it with almost zero NOx emissions due to very low nitrogen concentrations in the working fluid. The advanced zero emission power plants differ from a conventional gas turbine in the sense that its combustor is substituted with the mixed conductive membrane (MCM-reactor). The MCM-reactor is made up of the combustor, low temperature heat exchanger LTHX (referred to by some authors as air pre-heater the mixed conductive membrane responsible for oxygen transfer and the high temperature heat exchanger and in some layouts, the bleed gas heat exchanger. Air is taken in by the compressor and compressed to a temperature of about 723 Kelvin and pressure of 2 Mega-Pascals. The membrane area needed for oxygen transfer is reduced by increasing the temperature of 90% of the air using the LTHX; the temperature is also increased to facilitate oxygen transfer through the membrane. The air stream enters the LTHX through the transition duct leading to inlet of the LTHX. The temperature of the air stream is then increased to about 1150 K depending on the design point specification of the plant and the efficiency of the heat exchanging system. The amount of oxygen transported through the membrane is directly proportional to the temperature of air going through the membrane. The AZEP cycle was developed using the Fortran software and economic analysis was conducted using excel and Matlab followed by optimization case study. This paper discusses techno-economic analysis of four possible layouts of the AZEP cycle. The Simple bleed gas heat exchange layout (100 % CO2 capture), Bleed gas heat exchanger layout with flue gas turbine (100 % CO2 capture), Pre-expansion reheating layout (Sequential burning layout) – AZEP 85 % (85 % CO2 capture) and Pre-expansion reheating layout (Sequential burning layout) with flue gas turbine– AZEP 85 % (85 % CO2 capture). This paper discusses Montecarlo risk analysis of four possible layouts of the AZEP cycle.Keywords: gas turbine, global warming, green house gases, power plants
Procedia PDF Downloads 47264 Oncolytic Efficacy of Thymidine Kinase-Deleted Vaccinia Virus Strain Tiantan (oncoVV-TT) in Glioma
Authors: Seyedeh Nasim Mirbahari, Taha Azad, Mehdi Totonchi
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Oncolytic viruses, which only replicate in tumor cells, are being extensively studied for their use in cancer therapy. A particular virus known as the vaccinia virus, a member of the poxvirus family, has demonstrated oncolytic abilities glioma. Treating Glioma with traditional methods such as chemotherapy and radiotherapy is quite challenging. Even though oncolytic viruses have shown immense potential in cancer treatment, their effectiveness in glioblastoma treatment is still low. Therefore, there is a need to improve and optimize immunotherapies for better results. In this study, we have designed oncoVV-TT, which can more effectively target tumor cells while minimizing replication in normal cells by replacing the thymidine kinase gene with a luc-p2a-GFP gene expression cassette. Human glioblastoma cell line U251 MG, rat glioblastoma cell line C6, and non-tumor cell line HFF were plated at 105 cells in a 12-well plates in 2 mL of DMEM-F2 medium with 10% FBS added to each well. Then incubated at 37°C. After 16 hours, the cells were treated with oncoVV-TT at an MOI of 0.01, 0.1 and left in the incubator for a further 24, 48, 72 and 96 hours. Viral replication assay, fluorescence imaging and viability tests, including trypan blue and crystal violet, were conducted to evaluate the cytotoxic effect of oncoVV-TT. The finding shows that oncoVV-TT had significantly higher cytotoxic activity and proliferation rates in tumor cells in a dose and time-dependent manner, with the strongest effect observed in U251 MG. To conclude, oncoVV-TT has the potential to be a promising oncolytic virus for cancer treatment, with a more cytotoxic effect in human glioblastoma cells versus rat glioma cells. To assess the effectiveness of vaccinia virus-mediated viral therapy, we have tested U251mg and C6 tumor cell lines taken from human and rat gliomas, respectively. The study evaluated oncoVV-TT's ability to replicate and lyse cells and analyzed the survival rates of the tested cell lines when treated with different doses of oncoVV-TT. Additionally, we compared the sensitivity of human and mouse glioma cell lines to the oncolytic vaccinia virus. All experiments regarding viruses were conducted under biosafety level 2. We engineered a Vaccinia-based oncolytic virus called oncoVV-TT to replicate specifically in tumor cells. To propagate the oncoVV-TT virus, HeLa cells (5 × 104/well) were plated in 24-well plates and incubated overnight to attach to the bottom of the wells. Subsequently, 10 MOI virus was added. After 48 h, cells were harvested by scraping, and viruses were collected by 3 sequential freezing and thawing cycles followed by removal of cell debris by centrifugation (1500 rpm, 5 min). The supernatant was stored at −80 ◦C for the following experiments. To measure the replication of the virus in Hela, cells (5 × 104/well) were plated in 24-well plates and incubated overnight to attach to the bottom of the wells. Subsequently, 5 MOI virus or equal dilution of PBS was added. At the treatment time of 0 h, 24 h, 48 h, 72 h and 96 h, the viral titers were determined under the fluorescence microscope (BZ-X700; Keyence, Osaka, Japan). Fluorescence intensity was quantified using the imagej software according to the manufacturer’s protocol. For the isolation of single-virus clones, HeLa cells seeded in six-well plates (5×105 cells/well). After 24 h (100% confluent), the cells were infected with a 10-fold dilution series of TianTan green fluorescent protein (GFP)virus and incubated for 4 h. To examine the cytotoxic effect of oncoVV-TT virus ofn U251mg and C6 cell, trypan blue and crystal violet assay was used.Keywords: oncolytic virus, immune therapy, glioma, vaccinia virus
Procedia PDF Downloads 7963 The Use of Non-Parametric Bootstrap in Computing of Microbial Risk Assessment from Lettuce Consumption Irrigated with Contaminated Water by Sanitary Sewage in Infulene Valley
Authors: Mario Tauzene Afonso Matangue, Ivan Andres Sanchez Ortiz
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The Metropolitan area of Maputo (Mozambique Capital City) is located in semi-arid zone (800 mm annual rainfall) with 1101170 million inhabitants. On the west side, there are the flatlands of Infulene where the Mulauze River flows towards to the Indian Ocean, receiving at this site, the storm water contaminated with sanitary sewage from Maputo, transported through a concrete open channel. In Infulene, local communities grow salads crops such as tomato, onion, garlic, lettuce, and cabbage, which are then commercialized and consumed in several markets in Maputo City. Lettuce is the most daily consumed salad crop in different meals, generally in fast-foods, breakfasts, lunches, and dinners. However, the risk of infection by several pathogens due to the consumption of lettuce, using the Quantitative Microbial Risk Assessment (QMRA) tools, is still unknown since there are few studies or publications concerning to this matter in Mozambique. This work is aimed at determining the annual risk arising from the consumption of lettuce grown in Infulene valley, in Maputo, using QMRA tools. The exposure model was constructed upon the volume of contaminated water remaining in the lettuce leaves, the empirical relations between the number of pathogens and the indicator of microorganisms (E. coli), the consumption of lettuce (g) and reduction of pathogens (days). The reference pathogens were Vibrio cholerae, Cryptosporidium, norovirus, and Ascaris. The water quality samples (E. coli) were collected in the storm water channel from January 2016 to December 2018, comprising 65 samples, and the urban lettuce consumption data were collected through inquiry in Maputo Metropolis covering 350 persons. A non-parametric bootstrap was performed involving 10,000 iterations over the collected dataset, namely, water quality (E. coli) and lettuce consumption. The dose-response models were: Exponential for Cryptosporidium, Kummer Confluent hypergeomtric function (1F1) for Vibrio and Ascaris Gaussian hypergeometric function (2F1-(a,b;c;z) for norovirus. The annual infection risk estimates were performed using R 3.6.0 (CoreTeam) software by Monte Carlo (Latin hypercubes), a sampling technique involving 10,000 iterations. The annual infection risks values expressed by Median and the 95th percentile, per person per year (pppy) arising from the consumption of lettuce are as follows: Vibrio cholerae (1.00, 1.00), Cryptosporidium (3.91x10⁻³, 9.72x 10⁻³), nororvirus (5.22x10⁻¹, 9.99x10⁻¹) and Ascaris (2.59x10⁻¹, 9.65x10⁻¹). Thus, the consumption of the lettuce would result in greater risks than the tolerable levels ( < 10⁻³ pppy or 10⁻⁶ DALY) for all pathogens, and the Vibrio cholerae is the most virulent pathogens, according to the hit-single models followed by the Ascaris lumbricoides and norovirus. The sensitivity analysis carried out in this work pointed out that in the whole QMRA, the most important input variable was the reduction of pathogens (Spearman rank value was 0.69) between harvest and consumption followed by water quality (Spearman rank value was 0.69). The decision-makers (Mozambique Government) must strengthen the prevention measures related to pathogens reduction in lettuce (i.e., washing) and engage in wastewater treatment engineering.Keywords: annual infections risk, lettuce, non-parametric bootstrapping, quantitative microbial risk assessment tools
Procedia PDF Downloads 12062 Factors Associated with Risky Sexual Behaviour in Adolescent Girls and Young Women in Cambodia: A Systematic Review
Authors: Farwa Rizvi, Joanne Williams, Humaira Maheen, Elizabeth Hoban
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There is an increase in risky sexual behavior and unsafe sex in adolescent girls and young women aged 15 to 24 years in Cambodia, which negatively affects their reproductive health by increasing the risk of contracting sexually transmitted infections and unintended pregnancies. Risky sexual behavior includes ‘having sex at an early age, having multiple sexual partners, having sex while under the influence of alcohol or drugs, and unprotected sexual behaviors’. A systematic review of quantitative research conducted in Cambodia was undertaken, using the theoretical framework of the Social Ecological Model to identify the personal, social and cultural factors associated with risky sexual behavior and unsafe sex in young Cambodian women. PRISMA guidelines were used to search databases including Medline Complete, PsycINFO, CINAHL Complete, Academic Search Complete, Global Health, and Social Work Abstracts. Additional searches were conducted in Science Direct, Google Scholar and in the grey literature sources. A risk-of-bias tool developed explicitly for the systematic review of cross-sectional studies was used. Summary item on the overall risk of study bias after the inter-rater response showed that the risk-of-bias was high in two studies, moderate in one study and low in one study. The search strategy included a combination of subject terms and free text terms. The medical subject headings (MeSH) terms included were; contracept* or ‘birth control’ or ‘family planning’ or pregnan* or ‘safe sex’ or ‘protected intercourse’ or ‘unprotected intercourse’ or ‘protected sex’ or ‘unprotected sex’ or ‘risky sexual behaviour*’ or ‘abort*’ or ‘planned parenthood’ or ‘unplanned pregnancy’ AND ( barrier* or obstacle* or challenge* or knowledge or attitude* or factor* or determinant* or choic* or uptake or discontinu* or acceptance or satisfaction or ‘needs assessment’ or ‘non-use’ or ‘unmet need’ or ‘decision making’ ) AND Cambodia*. Initially, 300 studies were identified by using key words and finally, four quantitative studies were selected based on the inclusion criteria. The four studies were published between 2010 and 2016. The study participants ranged in age from 10-24 years, single or married, with 3 to 10 completed years of education. The mean age at sexual debut was reported to be 18 years. Using the perspective of the Social Ecological Model, risky sexual behavior was associated with individual-level factors including young age at sexual debut, low education, unsafe sex under the influence of alcohol and substance abuse, multiple sexual partners or transactional sex. Family level factors included living away from parents, orphan status and low levels of family support. Peer and partner level factors included peer delinquency and lack of condom use. Low socioeconomic status at the society level was also associated with risky sexual behaviour. There is scant research on sexual and reproductive health of adolescent girls and young women in Cambodia. Individual, family and social factors were significantly associated with risky sexual behaviour. More research is required to inform potential preventive strategies and policies that address young women’s sexual and reproductive health.Keywords: adolescents, high-risk sex, sexual activity, unplanned pregnancies
Procedia PDF Downloads 24661 A Copula-Based Approach for the Assessment of Severity of Illness and Probability of Mortality: An Exploratory Study Applied to Intensive Care Patients
Authors: Ainura Tursunalieva, Irene Hudson
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Continuous improvement of both the quality and safety of health care is an important goal in Australia and internationally. The intensive care unit (ICU) receives patients with a wide variety of and severity of illnesses. Accurately identifying patients at risk of developing complications or dying is crucial to increasing healthcare efficiency. Thus, it is essential for clinicians and researchers to have a robust framework capable of evaluating the risk profile of a patient. ICU scoring systems provide such a framework. The Acute Physiology and Chronic Health Evaluation III and the Simplified Acute Physiology Score II are ICU scoring systems frequently used for assessing the severity of acute illness. These scoring systems collect multiple risk factors for each patient including physiological measurements then render the assessment outcomes of individual risk factors into a single numerical value. A higher score is related to a more severe patient condition. Furthermore, the Mortality Probability Model II uses logistic regression based on independent risk factors to predict a patient’s probability of mortality. An important overlooked limitation of SAPS II and MPM II is that they do not, to date, include interaction terms between a patient’s vital signs. This is a prominent oversight as it is likely there is an interplay among vital signs. The co-existence of certain conditions may pose a greater health risk than when these conditions exist independently. One barrier to including such interaction terms in predictive models is the dimensionality issue as it becomes difficult to use variable selection. We propose an innovative scoring system which takes into account a dependence structure among patient’s vital signs, such as systolic and diastolic blood pressures, heart rate, pulse interval, and peripheral oxygen saturation. Copulas will capture the dependence among normally distributed and skewed variables as some of the vital sign distributions are skewed. The estimated dependence parameter will then be incorporated into the traditional scoring systems to adjust the points allocated for the individual vital sign measurements. The same dependence parameter will also be used to create an alternative copula-based model for predicting a patient’s probability of mortality. The new copula-based approach will accommodate not only a patient’s trajectories of vital signs but also the joint dependence probabilities among the vital signs. We hypothesise that this approach will produce more stable assessments and lead to more time efficient and accurate predictions. We will use two data sets: (1) 250 ICU patients admitted once to the Chui Regional Hospital (Kyrgyzstan) and (2) 37 ICU patients’ agitation-sedation profiles collected by the Hunter Medical Research Institute (Australia). Both the traditional scoring approach and our copula-based approach will be evaluated using the Brier score to indicate overall model performance, the concordance (or c) statistic to indicate the discriminative ability (or area under the receiver operating characteristic (ROC) curve), and goodness-of-fit statistics for calibration. We will also report discrimination and calibration values and establish visualization of the copulas and high dimensional regions of risk interrelating two or three vital signs in so-called higher dimensional ROCs.Keywords: copula, intensive unit scoring system, ROC curves, vital sign dependence
Procedia PDF Downloads 15260 Non-Mammalian Pattern Recognition Receptor from Rock Bream (Oplegnathus fasciatus): Genomic Characterization and Transcriptional Profile upon Bacterial and Viral Inductions
Authors: Thanthrige Thiunuwan Priyathilaka, Don Anushka Sandaruwan Elvitigala, Bong-Soo Lim, Hyung-Bok Jeong, Jehee Lee
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Toll like receptors (TLRs) are a phylogeneticaly conserved family of pattern recognition receptors, which participates in the host immune responses against various pathogens and pathogen derived mitogen. TLR21, a non-mammalian type, is almost restricted to the fish species even though those can be identified rarely in avians and amphibians. Herein, this study was carried out to identify and characterize TLR21 from rock bream (Oplegnathus fasciatus) designated as RbTLR21, at transcriptional and genomic level. In this study, the full length cDNA and genomic sequence of RbTLR21 was identified using previously constructed cDNA sequence database and BAC library, respectively. Identified RbTLR21 sequence was characterized using several bioinformatics tools. The quantitative real time PCR (qPCR) experiment was conducted to determine tissue specific expressional distribution of RbTLR21. Further, transcriptional modulation of RbTLR21 upon the stimulation with Streptococcus iniae (S. iniae), rock bream iridovirus (RBIV) and Edwardsiella tarda (E. tarda) was analyzed in spleen tissues. The complete coding sequence of RbTLR21 was 2919 bp in length which can encode a protein consisting of 973 amino acid residues with molecular mass of 112 kDa and theoretical isoelectric point of 8.6. The anticipated protein sequence resembled a typical TLR domain architecture including C-terminal ectodomain with 16 leucine rich repeats, a transmembrane domain, cytoplasmic TIR domain and signal peptide with 23 amino acid residues. Moreover, protein folding pattern prediction of RbTLR21 exhibited well-structured and folded ectodomain, transmembrane domain and cytoplasmc TIR domain. According to the pair wise sequence analysis data, RbTLR21 showed closest homology with orange-spotted grouper (Epinephelus coioides) TLR21with 76.9% amino acid identity. Furthermore, our phylogenetic analysis revealed that RbTLR21 shows a close evolutionary relationship with its ortholog from Danio rerio. Genomic structure of RbTLR21 consisted of single exon similar to its ortholog of zebra fish. Sevaral putative transcription factor binding sites were also identified in 5ʹ flanking region of RbTLR21. The RBTLR 21 was ubiquitously expressed in all the tissues we tested. Relatively, high expression levels were found in spleen, liver and blood tissues. Upon induction with rock bream iridovirus, RbTLR21 expression was upregulated at the early phase of post induction period even though RbTLR21 expression level was fluctuated at the latter phase of post induction period. Post Edwardsiella tarda injection, RbTLR transcripts were upregulated throughout the experiment. Similarly, Streptococcus iniae induction exhibited significant upregulations of RbTLR21 mRNA expression in the spleen tissues. Collectively, our findings suggest that RbTLR21 is indeed a homolog of TLR21 family members and RbTLR21 may be involved in host immune responses against bacterial and DNA viral infections.Keywords: rock bream, toll like receptor 21 (TLR21), pattern recognition receptor, genomic characterization
Procedia PDF Downloads 54159 Pharmacokinetics of First-Line Tuberculosis Drugs in South African Patients from Kwazulu-Natal: Effects of Pharmacogenetic Variation on Rifampicin and Isoniazid Concentrations
Authors: Anushka Naidoo, Veron Ramsuran, Maxwell Chirehwa, Paolo Denti, Kogieleum Naidoo, Helen McIlleron, Nonhlanhla Yende-Zuma, Ravesh Singh, Sinaye Ngcapu, Nesri Padayatachi
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Background: Despite efforts to introduce new drugs and shorter drug regimens for drug-susceptible tuberculosis (TB), the standard first-line treatment has not changed in over 50 years. Rifampicin, isoniazid, and pyrazinamide are critical components of the current standard treatment regimens. Some studies suggest that microbiologic failure and acquired drug resistance are primarily driven by low drug concentrations that result from pharmacokinetic (PK) variability independent of adherence to treatment. Wide between-patient pharmacokinetic variability for rifampin, isoniazid, and pyrazinamide has been reported in prior studies. There may be several reasons for this variability. However, genetic variability in genes coding for drug metabolizing and transporter enzymes have been shown to be a contributing factor for variable tuberculosis drug exposures. Objective: We describe the pharmacokinetics of first-line TB drugs rifampicin, isoniazid, and pyrazinamide and assess the effect of genetic variability in relevant selected drug metabolizing and transporter enzymes on pharmacokinetic parameters of isoniazid and rifampicin. Methods: We conducted the randomized-controlled Improving retreatment success TB trial in Durban, South Africa. The drug regimen included rifampicin, isoniazid, and pyrazinamide. Drug concentrations were measured in plasma, and concentration-time data were analysed using nonlinear-mixed-effects models to quantify the effects of relevant covariates and single nucleotide polymorphisms (SNP’s) of drug metabolizing and transporter genes on rifampicin, isoniazid and pyrazinamide exposure. A total of 25 SNP’s: four NAT2 (used to determine acetylator status), four SLCO1B1, three Pregnane X receptor (NR1), six ABCB1 and eight UGT1A, were selected for analysis in this study. Genotypes were determined for each of the SNP’s using a TaqMan® Genotyping OpenArray™. Results: Among fifty-eight patients studied; 41 (70.7%) were male, 97% black African, 42 (72.4%) HIV co-infected and 40 (95%) on efavirenz-based ART. Median weight, fat-free mass (FFM), and age at baseline were 56.9 kg (interquartile range, IQR: 51.1-65.2), 46.8 kg (IQR: 42.5-50.3) and 37 years (IQR: 31-42), respectively. The pharmacokinetics of rifampicin and pyrazinamide was best described using one-compartment models with first-order absorption and elimination, while for isoniazid two-compartment disposition was used. The median (interquartile range: IQR) AUC (h·mg/L) and Cmax (mg/L) for rifampicin, isoniazid, and pyrazinamide were; 25.62 (23.01-28.53) and 4.85 (4.36-5.40), 10.62 (9.20-12.25) and 2.79 (2.61-2.97), 345.74 (312.03-383.10) and 28.06 (25.01-31.52), respectively. Eighteen percent of patients were classified as rapid acetylators, and 34% and 43% as slow and intermediate acetylators, respectively. Rapid and intermediate acetylator status based on NAT 2 genotype resulted in 2.3 and 1.6 times higher isoniazid clearance than slow acetylators. We found no effects of the SLCO1B1 genotypes on rifampicin pharmacokinetics. Conclusion: Plasma concentrations of rifampicin, isoniazid, and pyrazinamide were low overall in our patients. Isoniazid clearance was high overall and as expected higher in rapid and intermediate acetylators resulting in lower drug exposures. In contrast to reports from previous South African or Ugandan studies, we did not find any effects of the SLCO1B1 or other genotypes tested on rifampicin PK. However, our findings are in keeping with more recent studies from Malawi and India emphasizing the need for geographically diverse and adequately powered studies. The clinical relevance of the low tuberculosis drug concentrations warrants further investigation.Keywords: rifampicin, isoniazid pharmacokinetics, genetics, NAT2, SLCO1B1, tuberculosis
Procedia PDF Downloads 18758 Optimized Electron Diffraction Detection and Data Acquisition in Diffraction Tomography: A Complete Solution by Gatan
Authors: Saleh Gorji, Sahil Gulati, Ana Pakzad
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Continuous electron diffraction tomography, also known as microcrystal electron diffraction (MicroED) or three-dimensional electron diffraction (3DED), is a powerful technique, which in combination with cryo-electron microscopy (cryo-ED), can provide atomic-scale 3D information about the crystal structure and composition of different classes of crystalline materials such as proteins, peptides, and small molecules. Unlike the well-established X-ray crystallography method, 3DED does not require large single crystals and can collect accurate electron diffraction data from crystals as small as 50 – 100 nm. This is a critical advantage as growing larger crystals, as required by X-ray crystallography methods, is often very difficult, time-consuming, and expensive. In most cases, specimens studied via 3DED method are electron beam sensitive, which means there is a limitation on the maximum amount of electron dose one can use to collect the required data for a high-resolution structure determination. Therefore, collecting data using a conventional scintillator-based fiber coupled camera brings additional challenges. This is because of the inherent noise introduced during the electron-to-photon conversion in the scintillator and transfer of light via the fibers to the sensor, which results in a poor signal-to-noise ratio and requires a relatively higher and commonly specimen-damaging electron dose rates, especially for protein crystals. As in other cryo-EM techniques, damage to the specimen can be mitigated if a direct detection camera is used which provides a high signal-to-noise ratio at low electron doses. In this work, we have used two classes of such detectors from Gatan, namely the K3® camera (a monolithic active pixel sensor) and Stela™ (that utilizes DECTRIS hybrid-pixel technology), to address this problem. The K3 is an electron counting detector optimized for low-dose applications (like structural biology cryo-EM), and Stela is also a counting electron detector but optimized for diffraction applications with high speed and high dynamic range. Lastly, data collection workflows, including crystal screening, microscope optics setup (for imaging and diffraction), stage height adjustment at each crystal position, and tomogram acquisition, can be one of the other challenges of the 3DED technique. Traditionally this has been all done manually or in a partly automated fashion using open-source software and scripting, requiring long hours on the microscope (extra cost) and extensive user interaction with the system. We have recently introduced Latitude® D in DigitalMicrograph® software, which is compatible with all pre- and post-energy-filter Gatan cameras and enables 3DED data acquisition in an automated and optimized fashion. Higher quality 3DED data enables structure determination with higher confidence, while automated workflows allow these to be completed considerably faster than before. Using multiple examples, this work will demonstrate how to direct detection electron counting cameras enhance 3DED results (3 to better than 1 Angstrom) for protein and small molecule structure determination. We will also show how Latitude D software facilitates collecting such data in an integrated and fully automated user interface.Keywords: continuous electron diffraction tomography, direct detection, diffraction, Latitude D, Digitalmicrograph, proteins, small molecules
Procedia PDF Downloads 10757 Effect of Cerebellar High Frequency rTMS on the Balance of Multiple Sclerosis Patients with Ataxia
Authors: Shereen Ismail Fawaz, Shin-Ichi Izumi, Nouran Mohamed Salah, Heba G. Saber, Ibrahim Mohamed Roushdi
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Background: Multiple sclerosis (MS) is a chronic, inflammatory, mainly demyelinating disease of the central nervous system, more common in young adults. Cerebellar involvement is one of the most disabling lesions in MS and is usually a sign of disease progression. It plays a major role in the planning, initiation, and organization of movement via its influence on the motor cortex and corticospinal outputs. Therefore, it contributes to controlling movement, motor adaptation, and motor learning, in addition to its vast connections with other major pathways controlling balance, such as the cerebellopropriospinal pathways and cerebellovestibular pathways. Hence, trying to stimulate the cerebellum by facilitatory protocols will add to our motor control and balance function. Non-invasive brain stimulation, both repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), has recently emerged as effective neuromodulators to influence motor and nonmotor functions of the brain. Anodal tDCS has been shown to improve motor skill learning and motor performance beyond the training period. Similarly, rTMS, when used at high frequency (>5 Hz), has a facilitatory effect on the motor cortex. Objective: Our aim was to determine the effect of high-frequency rTMS over the cerebellum in improving balance and functional ambulation of multiple sclerosis patients with Ataxia. Patients and methods: This was a randomized single-blinded placebo-controlled prospective trial on 40 patients. The active group (N=20) received real rTMS sessions, and the control group (N=20) received Sham rTMS using a placebo program designed for this treatment. Both groups received 12 sessions of high-frequency rTMS over the cerebellum, followed by an intensive exercise training program. Sessions were given three times per week for four weeks. The active group protocol had a frequency of 10 Hz rTMS over the cerebellar vermis, work period 5S, number of trains 25, and intertrain interval 25s. The total number of pulses was 1250 pulses per session. The control group received Sham rTMS using a placebo program designed for this treatment. Both groups of patients received an intensive exercise program, which included generalized strengthening exercises, endurance and aerobic training, trunk abdominal exercises, generalized balance training exercises, and task-oriented training such as Boxing. As a primary outcome measure the Modified ICARS was used. Static Posturography was done with: Patients were tested both with open and closed eyes. Secondary outcome measures included the expanded Disability Status Scale (EDSS) and 8 Meter walk test (8MWT). Results: The active group showed significant improvements in all the functional scales, modified ICARS, EDSS, and 8-meter walk test, in addition to significant differences in static Posturography with open eyes, while the control group did not show such differences. Conclusion: Cerebellar high-frequency rTMS could be effective in the functional improvement of balance in MS patients with ataxia.Keywords: brain neuromodulation, high frequency rTMS, cerebellar stimulation, multiple sclerosis, balance rehabilitation
Procedia PDF Downloads 9056 Thermally Conductive Polymer Nanocomposites Based on Graphene-Related Materials
Authors: Alberto Fina, Samuele Colonna, Maria del Mar Bernal, Orietta Monticelli, Mauro Tortello, Renato Gonnelli, Julio Gomez, Chiara Novara, Guido Saracco
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Thermally conductive polymer nanocomposites are of high interest for several applications including low-temperature heat recovery, heat exchangers in a corrosive environment and heat management in electronics and flexible electronics. In this paper, the preparation of thermally conductive nanocomposites exploiting graphene-related materials is addressed, along with their thermal characterization. In particular, correlations between 1- chemical and physical features of the nanoflakes and 2- processing conditions with the heat conduction properties of nanocomposites is studied. Polymers are heat insulators; therefore, the inclusion of conductive particles is the typical solution to obtain a sufficient thermal conductivity. In addition to traditional microparticles such as graphite and ceramics, several nanoparticles have been proposed, including carbon nanotubes and graphene, for the use in polymer nanocomposites. Indeed, thermal conductivities for both carbon nanotubes and graphenes were reported in the wide range of about 1500 to 6000 W/mK, despite such property may decrease dramatically as a function of the size, number of layers, the density of topological defects, re-hybridization defects as well as on the presence of impurities. Different synthetic techniques have been developed, including mechanical cleavage of graphite, epitaxial growth on SiC, chemical vapor deposition, and liquid phase exfoliation. However, the industrial scale-up of graphene, defined as an individual, single-atom-thick sheet of hexagonally arranged sp2-bonded carbons still remains very challenging. For large scale bulk applications in polymer nanocomposites, some graphene-related materials such as multilayer graphenes (MLG), reduced graphene oxide (rGO) or graphite nanoplatelets (GNP) are currently the most interesting graphene-based materials. In this paper, different types of graphene-related materials were characterized for their chemical/physical as well as for thermal properties of individual flakes. Two selected rGOs were annealed at 1700°C in vacuum for 1 h to reduce defectiveness of the carbon structure. Thermal conductivity increase of individual GNP with annealing was assessed via scanning thermal microscopy. Graphene nano papers were prepared from both conventional RGO and annealed RGO flakes. Characterization of the nanopapers evidenced a five-fold increase in the thermal diffusivity on the nano paper plane for annealed nanoflakes, compared to pristine ones, demonstrating the importance of structural defectiveness reduction to maximize the heat dissipation performance. Both pristine and annealed RGO were used to prepare polymer nanocomposites, by melt reactive extrusion. Thermal conductivity showed two- to three-fold increase in the thermal conductivity of the nanocomposite was observed for high temperature treated RGO compared to untreated RGO, evidencing the importance of using low defectivity nanoflakes. Furthermore, the study of different processing paremeters (time, temperature, shear rate) during the preparation of poly (butylene terephthalate) nanocomposites evidenced a clear correlation with the dispersion and fragmentation of the GNP nanoflakes; which in turn affected the thermal conductivity performance. Thermal conductivity of about 1.7 W/mK, i.e. one order of magnitude higher than for pristine polymer, was obtained with 10%wt of annealed GNPs, which is in line with state of the art nanocomposites prepared by more complex and less upscalable in situ polymerization processes.Keywords: graphene, graphene-related materials, scanning thermal microscopy, thermally conductive polymer nanocomposites
Procedia PDF Downloads 26855 Xen45 Gel Implant in Open Angle Glaucoma: Efficacy, Safety and Predictors of Outcome
Authors: Fossarello Maurizio, Mattana Giorgio, Tatti Filippo.
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The most widely performed surgical procedure in Open-Angle Glaucoma (OAG) is trabeculectomy. Although this filtering procedure is extremely effective, surgical failure and postoperative complications are reported. Due to the its invasive nature and possible complications, trabeculectomy is usually reserved, in practice, for patients who are refractory to medical and laser therapy. Recently, a number of micro-invasive surgical techniques (MIGS: Micro-Invasive Glaucoma Surgery), have been introduced in clinical practice. They meet the criteria of micro-incisional approach, minimal tissue damage, short surgical time, reliable IOP reduction, extremely high safety profile and rapid post-operative recovery. Xen45 Gel Implant (Allergan, Dublin, Ireland) is one of the MIGS alternatives, and consists in a porcine gelatin tube designed to create an aqueous flow from the anterior chamber to the subconjunctival space, bypassing the resistance of the trabecular meshwork. In this study we report the results of this technique as a favorable option in the treatment of OAG for its benefits in term of efficacy and safety, either alone or in combination with cataract surgery. This is a retrospective, single-center study conducted in consecutive OAG patients, who underwent Xen45 Gel Stent implantation alone or in combination with phacoemulsification, from October 2018 to June 2019. The primary endpoint of the study was to evaluate the reduction of both IOP and number of antiglaucoma medications at 12 months. The secondary endpoint was to correlate filtering bleb morphology evaluated by means of anterior segment OCT with efficacy in IOP lowering and eventual further procedures requirement. Data were recorded on Microsoft Excel and study analysis was performed using Microsoft Excel and SPSS (IBM). Mean values with standard deviations were calculated for IOPs and number of antiglaucoma medications at all points. Kolmogorov-Smirnov test showed that IOP followed a normal distribution at all time, therefore the paired Student’s T test was used to compare baseline and postoperative mean IOP. Correlation between postoperative Day 1 IOP and Month 12 IOP was evaluated using Pearson coefficient. Thirty-six eyes of 36 patients were evaluated. As compared to baseline, mean IOP and the mean number of antiglaucoma medications significantly decreased from 27,33 ± 7,67 mmHg to 16,3 ± 2,89 mmHg (38,8% reduction) and from 2,64 ± 1,39 to 0,42 ± 0,8 (84% reduction), respectively, at 12 months after surgery (both p < 0,001). According to bleb morphology, eyes were divided in uniform group (n=8, 22,2%), subconjunctival separation group (n=5, 13,9%), microcystic multiform group (n=9, 25%) and multiple internal layer group (n=14, 38,9%). Comparing to baseline, there was no significative difference in IOP between the 4 groups at month 12 follow-up visit. Adverse events included bleb function decrease (n=14, 38,9%), hypotony (n=8, 22,2%) and choroidal detachment (n=2, 5,6%). All eyes presenting bleb flattening underwent needling and MMC injection. The higher percentage of patients that required secondary needling was in the uniform group (75%), with a significant difference between the groups (p=0,03). Xen45 gel stent, either alone or in combination with phacoemulsification, provided a significant lowering in both IOP and medical antiglaucoma treatment and an elevated safety profile.Keywords: anterior segment OCT, bleb morphology, micro-invasive glaucoma surgery, open angle glaucoma, Xen45 gel implant
Procedia PDF Downloads 14154 Advocating for Indigenous Music in Latin American Music Education
Authors: Francisco Luis Reyes
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European colonization had a profound impact on Latin America. The influence of the old continent can be perceived in the culture, religion, and language of the region as well as the beliefs and attitudes of the population. Music education is not an exception to this phenomenon. With Europeans controlling cultural life and erecting educational institutions across the continent for several centuries, Western European Art Music (WEAM) has polarized music learning in formal spaces. In contrast, the musics from the indigenous population, the African slaves, and the ones that emerged as a result of the cultural mélanges have largely been excluded from primary and secondary schooling. The purpose of this paper is to suggest the inclusion of indigenous music education in primary and secondary music education. The paper employs a philosophical inquiry in order to achieve this aim. Philosophical inquiry seeks to uncover and examine individuals' unconscious beliefs, principles, values, and assumptions to envision potential possibilities. This involves identifying and describing issues within current music teaching and learning practices. High-quality philosophical research tackles problems that are sufficiently narrow (addressing a specific aspect of a single complex topic), realistic (reflecting the experiences of music education), and significant (addressing a widespread and timely issue). Consequently, this methodological approach fits this topic, as the research addresses the omnipresence of WEAM in Latin American music education, the exclusion of indigenous music, and argues about the transformational impact said artistic expressions can have on practices in the region. The paper initially addresses how WEAM became ubiquitous in the region by recounting historical events, and adressing the issues other types of music face entering higher education. According to Shifres and Rosabal-Coto (2017) Latin America still upholds the musical heritage of their colonial period, and its formal music education institutions promote the European ontology instilled during European expansion. In accordance, the work of Reyes and Lorenzo-Quiles (2024), and Soler, Lorenzo-Quiles, and Hargreaves (2014), demonstrate how music institutions in the region uphold foreign narratives. Their studies show that music programs in Puerto Rico and Colombia instruct students in WEAM as well as require skills in said art form to enter the profession, just like other authors have argued (Cain & Walden, 2019, Walden, 2016). Subsequently, the research explains the issues faced by prospective music educators that do not practice WEAM. Roberts (1991a, 1991b, 1993), Green (2012) have found that music education students that do not adhere to the musical culture of their institution, are less likely to finish their degrees. Hence, practicioners of tradional musics might feel out of place in the environment. The ubiquity of WEAM and the exclusion of traditional musics of the region, provide the primary challenges to the inclusion of indigenous musics in formal spaces in primary and secondary education. The presentation then laids the framework for the inclusion indigenous music, and conclusively offers examples of how the musical expressions from the continent can improove the music education practices of the region. As an ending, the article highlights the benefits of these musics that are lacking in current practices.Keywords: indigenous music education, postmodern music education, decolonization in music education, music education practice, Latin American music education
Procedia PDF Downloads 3353 Hybrid Materials on the Basis of Magnetite and Magnetite-Gold Nanoparticles for Biomedical Application
Authors: Mariia V. Efremova, Iana O. Tcareva, Anastasia D. Blokhina, Ivan S. Grebennikov, Anastasia S. Garanina, Maxim A. Abakumov, Yury I. Golovin, Alexander G. Savchenko, Alexander G. Majouga, Natalya L. Klyachko
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During last decades magnetite nanoparticles (NPs) attract a deep interest of scientists due to their potential application in therapy and diagnostics. However, magnetite nanoparticles are toxic and non-stable in physiological conditions. To solve these problems, we decided to create two types of hybrid systems based on magnetite and gold which is inert and biocompatible: gold as a shell material (first type) and gold as separate NPs interfacially bond to magnetite NPs (second type). The synthesis of the first type hybrid nanoparticles was carried out as follows: Magnetite nanoparticles with an average diameter of 9±2 nm were obtained by co-precipitation of iron (II, III) chlorides then they were covered with gold shell by iterative reduction of hydrogen tetrachloroaurate with hydroxylamine hydrochloride. According to the TEM, ICP MS and EDX data, final nanoparticles had an average diameter of 31±4 nm and contained iron even after hydrochloric acid treatment. However, iron signals (K-line, 7,1 keV) were not localized so we can’t speak about one single magnetic core. Described nanoparticles covered with mercapto-PEG acid were non-toxic for human prostate cancer PC-3/ LNCaP cell lines (more than 90% survived cells as compared to control) and had high R2-relaxivity rates (>190 mМ-1s-1) that exceed the transverse relaxation rate of commercial MRI-contrasting agents. These nanoparticles were also used for chymotrypsin enzyme immobilization. The effect of alternating magnetic field on catalytic properties of chymotrypsin immobilized on magnetite nanoparticles, notably the slowdown of catalyzed reaction at the level of 35-40 % was found. The synthesis of the second type hybrid nanoparticles also involved two steps. Firstly, spherical gold nanoparticles with an average diameter of 9±2 nm were synthesized by the reduction of hydrogen tetrachloroaurate with oleylamine; secondly, they were used as seeds during magnetite synthesis by thermal decomposition of iron pentacarbonyl in octadecene. As a result, so-called dumbbell-like structures were obtained where magnetite (cubes with 25±6 nm diagonal) and gold nanoparticles were connected together pairwise. By HRTEM method (first time for this type of structure) an epitaxial growth of magnetite nanoparticles on gold surface with co-orientation of (111) planes was discovered. These nanoparticles were transferred into water by means of block-copolymer Pluronic F127 then loaded with anti-cancer drug doxorubicin and also PSMA-vector specific for LNCaP cell line. Obtained nanoparticles were found to have moderate toxicity for human prostate cancer cells and got into the intracellular space after 45 minutes of incubation (according to fluorescence microscopy data). These materials are also perspective from MRI point of view (R2-relaxivity rates >70 mМ-1s-1). Thereby, in this work magnetite-gold hybrid nanoparticles, which have a strong potential for biomedical application, particularly in targeted drug delivery and magnetic resonance imaging, were synthesized and characterized. That paves the way to the development of special medicine types – theranostics. The authors knowledge financial support from Ministry of Education and Science of the Russian Federation (14.607.21.0132, RFMEFI60715X0132). This work was also supported by Grant of Ministry of Education and Science of the Russian Federation К1-2014-022, Grant of Russian Scientific Foundation 14-13-00731 and MSU development program 5.13.Keywords: drug delivery, magnetite-gold, MRI contrast agents, nanoparticles, toxicity
Procedia PDF Downloads 38252 Application of Electrical Resistivity Surveys on Constraining Causes of Highway Pavement Failure along Ajaokuta-Anyigba Road, North Central Nigeria
Authors: Moroof, O. Oloruntola, Sunday Oladele, Daniel, O. Obasaju, Victor, O Ojekunle, Olateju, O. Bayewu, Ganiyu, O. Mosuro
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Integrated geophysical methods involving Vertical Electrical Sounding (VES) and 2D resistivity survey were deployed to gain an insight into the influence of the two varying rock types (mica-schist and granite gneiss) underlying the road alignment to the incessant highway failure along Ajaokuta-Anyigba, North-central Nigeria. The highway serves as a link-road for the single largest cement factory in Africa (Dangote Cement Factory) and two major ceramic industries to the capital (Abuja) via Lokoja. 2D Electrical Resistivity survey (Dipole-Dipole Array) and Vertical Electrical Sounding (VES) (Schlumberger array) were employed. Twenty-two (22) 2D profiles were occupied, twenty (20) conducted about 1 m away from the unstable section underlain by mica-schist with profile length each of approximately 100 m. Two (2) profiles were conducted about 1 m away from the stable section with a profile length of 100 m each due to barriers caused by the drainage system and outcropping granite gneiss at the flanks of the road. A spacing of 2 m was used for good image resolution of the near-surface. On each 2D profile, a range of 1-3 VES was conducted; thus, forty-eight (48) soundings were acquired. Partial curve matching and WinResist software were used to obtain the apparent and true resistivity values of the 1D survey, while DiprofWin software was used for processing the 2-D survey. Two exposed lithologic sections caused by abandoned river channels adjacent to two profiles as well as the knowledge of the geology of the area helped to constrain the VES and 2D processing and interpretation. Generally, the resistivity values obtained reflect the parent rock type, degree of weathering, moisture content and competency of the tested area. Resistivity values < 100; 100 – 950; 1000 – 2000 and > 2500 ohms-m were interpreted as clay, weathered layer, partly weathered layer and fresh basement respectively. The VES results and 2-D resistivity structures along the unstable segment showed similar lithologic characteristics and sequences dominated by clayey substratum for depths range of 0 – 42.2 m. The clayey substratum is a product of intensive weathering of the parent rock (mica-schist) and constitutes weak foundation soils, causing highway failure. This failure is further exacerbated by several heavy-duty trucks which ply the section round the clock due to proximity to two major ceramic industries in the state and lack of drainage system. The two profiles on the stable section show 2D structures that are remarkably different from those of the unstable section with very thin topsoils, higher resistivity weathered substratum (indicating the presence of coarse fragments from the parent rock) and shallow depth to the basement (1.0 – 7. 1 m). Also, the presence of drainage and lower volume of heavy-duty trucks are contributors to the pavement stability of this section of the highway. The resistivity surveys effectively delineated two contrasting soil profiles of the subbase/subgrade that reflect variation in the mineralogy of underlying parent rocks.Keywords: clay, geophysical methods, pavement, resistivity
Procedia PDF Downloads 16851 Preliminary Results on a Study of Antimicrobial Susceptibility Testing of Bacillus anthracis Strains Isolated during Anthrax Outbreaks in Italy from 2001 to 2017
Authors: Viviana Manzulli, Luigina Serrecchia, Adelia Donatiello, Valeria Rondinone, Sabine Zange, Alina Tscherne, Antonio Parisi, Antonio Fasanella
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Anthrax is a zoonotic disease that affects a wide range of animal species (primarily ruminant herbivores), and can be transmitted to humans through consumption or handling of contaminated animal products. The etiological agent B.anthracis is able to survive in unfavorable environmental conditions by forming endospore which remain viable in the soil for many decades. Furthermore, B.anthracis is considered as one of the most feared agents to be potentially misused as a biological weapon and the importance of the disease and its treatment in humans has been underscored before the bioterrorism events in the United States in 2001. Due to the often fatal outcome of human cases, antimicrobial susceptibility testing plays especially in the management of anthrax infections an important role. In Italy, animal anthrax is endemic (predominantly found in the southern regions and on islands) and is characterized by sporadic outbreaks occurring mainly during summer. Between 2012 and 2017 single human cases of cutaneous anthrax occurred. In this study, 90 diverse strains of B.anthracis, isolated in Italy from 2001 to 2017, were screened to their susceptibility to sixteen clinically relevant antimicrobial agents by using the broth microdilution method. B.anthracis strains selected for this study belong to the strain collection stored at the Anthrax Reference Institute of Italy located inside the Istituto Zooprofilattico Sperimentale of Puglia and Basilicata. The strains were isolated at different time points and places from various matrices (human, animal and environmental). All strains are a representative of over fifty distinct MLVA 31 genotypes. The following antibiotics were used for testing: gentamicin, ceftriaxone, streptomycin, penicillin G, clindamycin, chloramphenicol, vancomycin, linezolid, cefotaxime, tetracycline, erythromycin, rifampin, amoxicillin, ciprofloxacin, doxycycline and trimethoprim. A standard concentration of each antibiotic was prepared in a specific diluent, which were then twofold serial diluted. Therefore, each wells contained: bacterial suspension of 1–5x104 CFU/mL in Mueller-Hinton Broth (MHB), the antibiotic to be tested at known concentration and resazurin, an indicator of cell growth. After incubation overnight at 37°C, the wells were screened for color changes caused by the resazurin: a change from purple to pink/colorless indicated cell growth. The lowest concentration of antibiotic that prevented growth represented the minimal inhibitory concentration (MIC). This study suggests that B.anthracis remains susceptible in vitro to many antibiotics, in addition to doxycycline (MICs ≤ 0,03 µg/ml), ciprofloxacin (MICs ≤ 0,03 µg/ml) and penicillin G (MICs ≤ 0,06 µg/ml), recommend by CDC for the treatment of human cases and for prophylactic use after exposure to the spores. In fact, the good activity of gentamicin (MICs ≤ 0,25 µg/ml), streptomycin (MICs ≤ 1 µg/ml), clindamycin (MICs ≤ 0,125 µg/ml), chloramphenicol(MICs ≤ 4 µg/ml), vancomycin (MICs ≤ 2 µg/ml), linezolid (MICs ≤ 2 µg/ml), tetracycline (MICs ≤ 0,125 µg/ml), erythromycin (MICs ≤ 0,25 µg/ml), rifampin (MICs ≤ 0,25 µg/ml), amoxicillin (MICs ≤ 0,06 µg/ml), towards all tested B.anthracis strains demonstrates an appropriate alternative choice for prophylaxis and/or treatment. All tested B.anthracis strains showed intermediate susceptibility to the cephalosporins (MICs ≥ 16 µg/ml) and resistance to trimethoprim (MICs ≥ 128 µg/ml).Keywords: Bacillus anthracis, antibiotic susceptibility, treatment, minimum inhibitory concentration
Procedia PDF Downloads 21350 Effect of Preoxidation on the Effectiveness of Gd₂O₃ Nanoparticles Applied as a Source of Active Element in the Crofer 22 APU Coated with a Protective-conducting Spinel Layer
Authors: Łukasz Mazur, Kamil Domaradzki, Maciej Bik, Tomasz Brylewski, Aleksander Gil
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Interconnects used in solid oxide fuel and electrolyzer cells (SOFCₛ/SOECs) serve several important functions, and therefore interconnect materials must exhibit certain properties. Their thermal expansion coefficient needs to match that of the ceramic components of these devices – the electrolyte, anode and cathode. Interconnects also provide structural rigidity to the entire device, which is why interconnect materials must exhibit sufficient mechanical strength at high temperatures. Gas-tightness is also a prerequisite since they separate gas reagents, and they also must provide very good electrical contact between neighboring cells over the entire operating time. High-chromium ferritic steels meets these requirements to a high degree but are affected by the formation of a Cr₂O₃ scale, which leads to increased electrical resistance. The final criterion for interconnect materials is chemical inertness in relation to the remaining cell components. In the case of ferritic steels, this has proved difficult due to the formation of volatile and reactive oxyhydroxides observed when Cr₂O3 is exposed to oxygen and water vapor. This process is particularly harmful on the cathode side in SOFCs and the anode side in SOECs. To mitigate this, protective-conducting ceramic coatings can be deposited on an interconnect's surface. The area-specific resistance (ASR) of a single interconnect cannot exceed 0.1 m-2 at any point of the device's operation. The rate at which the CrO₃ scale grows on ferritic steels can be reduced significantly via the so-called reactive element effect (REE). Research has shown that the deposition of Gd₂O₃ nanoparticles on the surface of the Crofer 22 APU, already modified using a protective-conducting spinel layer, further improves the oxidation resistance of this steel. However, the deposition of the manganese-cobalt spinel layer is a rather complex process and is performed at high temperatures in reducing and oxidizing atmospheres. There was thus reason to believe that this process may reduce the effectiveness of Gd₂O₃ nanoparticles added as an active element source. The objective of the present study was, therefore, to determine any potential impact by introducing a preoxidation stage after the nanoparticle deposition and before the steel is coated with the spinel. This should have allowed the nanoparticles to incorporate into the interior of the scale formed on the steel. Different samples were oxidized for 7000 h in air at 1073 K under quasi-isothermal conditions. The phase composition, chemical composition, and microstructure of the oxidation products formed on the samples were determined using X-ray diffraction, Raman spectroscopy, and scanning electron microscopy combined with energy-dispersive X-ray spectroscopy. A four-point, two-probe DC method was applied to measure ASR. It was found that coating deposition does indeed reduce the beneficial effect of Gd₂O₃ addition, since the smallest mass gain and the lowest ASR value were determined for the sample for which the additional preoxidation stage had been performed. It can be assumed that during this stage, gadolinium incorporates into and segregates at grain boundaries in the thin Cr₂O₃ that is forming. This allows the Gd₂O₃ nanoparticles to be a more effective source of the active element.Keywords: interconnects, oxide nanoparticles, reactive element effect, SOEC, SOFC
Procedia PDF Downloads 8449 Assessing Organizational Resilience Capacity to Flooding: Index Development and Application to Greek Small & Medium-Sized Enterprises
Authors: Antonis Skouloudis, Konstantinos Evangelinos, Walter Leal-Filho, Panagiotis Vouros, Ioannis Nikolaou
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Organizational resilience capacity to extreme weather events (EWEs) has sparked a growth in scholarly attention over the past decade as an essential aspect in business continuity management, with supporting evidence for this claim to suggest that it retains a key role in successful responses to adverse situations, crises and shocks. Small and medium-sized enterprises (SMEs) are more vulnerable to face floods compared to their larger counterparts, so they are disproportionately affected by such extreme weather events. The limited resources at their disposal, the lack of time and skills all conduce to inadequate preparedness to challenges posed by floods. SMEs tend to plan in the short-term, reacting to circumstances as they arise and focussing on their very survival. Likewise, they share less formalised structures and codified policies while they are most usually owner-managed, resulting in a command-and-control management culture. Such characteristics result in them having limited opportunities to recover from flooding and quickly turnaround their operation from a loss making to a profit making one. Scholars frame the capacity of business entities to be resilient upon an EWE disturbance (such as flash floods) as the rate of recovery and restoration of organizational performance to pre-disturbance conditions, the amount of disturbance (i.e. threshold level) a business can absorb before losing structural and/or functional components that will alter or cease operation, as well as the extent to which the organization maintains its function (i.e. impact resistance) before performance levels are driven to zero. Nevertheless, while it seems to be accepted as an essential trait of firms effectively transcending uncertain conditions, research deconstructing the enabling conditions and/or inhibitory factors of SMEs resilience capacity to natural hazards is still sparse, fragmentary and mostly fuelled by anecdotal evidence or normative assumptions. Focusing on the individual level of analysis, i.e. the individual enterprise and its endeavours to succeed, the emergent picture from this relatively new research strand delineates the specification of variables, conceptual relationships or dynamic boundaries of resilience capacity components in an attempt to provide prescriptions for policy-making as well as business management. This study will present the development of a flood resilience capacity index (FRCI) and its application to Greek SMEs. The proposed composite indicator pertains to cognitive, behavioral/managerial and contextual factors that influence an enterprise’s ability to shape effective responses to meet flood challenges. Through the proposed indicator-based approach, an analytical framework is set forth that will help standardize such assessments with the overarching aim of reducing the vulnerability of SMEs to flooding. This will be achieved by identifying major internal and external attributes explaining resilience capacity which is particularly important given the limited resources these enterprises have and that they tend to be primary sources of vulnerabilities in supply chain networks, generating Single Points of Failure (SPOF).Keywords: Floods, Small & Medium-Sized enterprises, organizational resilience capacity, index development
Procedia PDF Downloads 19048 Simulation of Multistage Extraction Process of Co-Ni Separation Using Ionic Liquids
Authors: Hongyan Chen, Megan Jobson, Andrew J. Masters, Maria Gonzalez-Miquel, Simon Halstead, Mayri Diaz de Rienzo
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Ionic liquids offer excellent advantages over conventional solvents for industrial extraction of metals from aqueous solutions, where such extraction processes bring opportunities for recovery, reuse, and recycling of valuable resources and more sustainable production pathways. Recent research on the use of ionic liquids for extraction confirms their high selectivity and low volatility, but there is relatively little focus on how their properties can be best exploited in practice. This work addresses gaps in research on process modelling and simulation, to support development, design, and optimisation of these processes, focusing on the separation of the highly similar transition metals, cobalt, and nickel. The study exploits published experimental results, as well as new experimental results, relating to the separation of Co and Ni using trihexyl (tetradecyl) phosphonium chloride. This extraction agent is attractive because it is cheaper, more stable and less toxic than fluorinated hydrophobic ionic liquids. This process modelling work concerns selection and/or development of suitable models for the physical properties, distribution coefficients, for mass transfer phenomena, of the extractor unit and of the multi-stage extraction flowsheet. The distribution coefficient model for cobalt and HCl represents an anion exchange mechanism, supported by the literature and COSMO-RS calculations. Parameters of the distribution coefficient models are estimated by fitting the model to published experimental extraction equilibrium results. The mass transfer model applies Newman’s hard sphere model. Diffusion coefficients in the aqueous phase are obtained from the literature, while diffusion coefficients in the ionic liquid phase are fitted to dynamic experimental results. The mass transfer area is calculated from the surface to mean diameter of liquid droplets of the dispersed phase, estimated from the Weber number inside the extractor. New experiments measure the interfacial tension between the aqueous and ionic phases. The empirical models for predicting the density and viscosity of solutions under different metal loadings are also fitted to new experimental data. The extractor is modelled as a continuous stirred tank reactor with mass transfer between the two phases and perfect phase separation of the outlet flows. A multistage separation flowsheet simulation is set up to replicate a published experiment and compare model predictions with the experimental results. This simulation model is implemented in gPROMS software for dynamic process simulation. The results of single stage and multi-stage flowsheet simulations are shown to be in good agreement with the published experimental results. The estimated diffusion coefficient of cobalt in the ionic liquid phase is in reasonable agreement with published data for the diffusion coefficients of various metals in this ionic liquid. A sensitivity study with this simulation model demonstrates the usefulness of the models for process design. The simulation approach has potential to be extended to account for other metals, acids, and solvents for process development, design, and optimisation of extraction processes applying ionic liquids for metals separations, although a lack of experimental data is currently limiting the accuracy of models within the whole framework. Future work will focus on process development more generally and on extractive separation of rare earths using ionic liquids.Keywords: distribution coefficient, mass transfer, COSMO-RS, flowsheet simulation, phosphonium
Procedia PDF Downloads 19047 Production of Insulin Analogue SCI-57 by Transient Expression in Nicotiana benthamiana
Authors: Adriana Muñoz-Talavera, Ana Rosa Rincón-Sánchez, Abraham Escobedo-Moratilla, María Cristina Islas-Carbajal, Miguel Ángel Gómez-Lim
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The highest rates of diabetes incidence and prevalence worldwide will increase the number of diabetic patients requiring insulin or insulin analogues. Then, current production systems would not be sufficient to meet the future market demands. Therefore, developing efficient expression systems for insulin and insulin analogues are needed. In addition, insulin analogues with better pharmacokinetics and pharmacodynamics properties and without mitogenic potential will be required. SCI-57 (single chain insulin-57) is an insulin analogue having 10 times greater affinity to the insulin receptor, higher resistance to thermal degradation than insulin, native mitogenicity and biological effect. Plants as expression platforms have been used to produce recombinant proteins because of their advantages such as cost-effectiveness, posttranslational modifications, absence of human pathogens and high quality. Immunoglobulin production with a yield of 50% has been achieved by transient expression in Nicotiana benthamiana (Nb). The aim of this study is to produce SCI-57 by transient expression in Nb. Methodology: DNA sequence encoding SCI-57 was cloned in pICH31070. This construction was introduced into Agrobacterium tumefaciens by electroporation. The resulting strain was used to infiltrate leaves of Nb. In order to isolate SCI-57, leaves from transformed plants were incubated 3 hours with the extraction buffer therefore filtrated to remove solid material. The resultant protein solution was subjected to anion exchange chromatography on an FPLC system and ultrafiltration to purify SCI-57. Detection of SCI-57 was made by electrophoresis pattern (SDS-PAGE). Protein band was digested with trypsin and the peptides were analyzed by Liquid chromatography tandem-mass spectrometry (LC-MS/MS). A purified protein sample (20µM) was analyzed by ESI-Q-TOF-MS to obtain the ionization pattern and the exact molecular weight determination. Chromatography pattern and impurities detection were performed using RP-HPLC using recombinant insulin as standard. The identity of the SCI-57 was confirmed by anti-insulin ELISA. The total soluble protein concentration was quantified by Bradford assay. Results: The expression cassette was verified by restriction mapping (5393 bp fragment). The SDS-PAGE of crude leaf extract (CLE) of transformed plants, revealed a protein of about 6.4 kDa, non-present in CLE of untransformed plants. The LC-MS/MS results displayed one peptide with a high score that matches SCI-57 amino acid sequence in the sample, confirming the identity of SCI-57. From the purified SCI-57 sample (PSCI-57) the most intense charge state was 1069 m/z (+6) on the displayed ionization pattern corresponding to the molecular weight of SCI-57 (6412.6554 Da). The RP-HPLC of the PSCI-57 shows the presence of a peak with similar retention time (rt) and UV spectroscopic profile to the insulin standard (SCI-57 rt=12.96 and insulin rt=12.70 min). The collected SCI-57 peak had ELISA signal. The total protein amount in CLE from transformed plants was higher compared to untransformed plants. Conclusions: Our results suggest the feasibility to produce insulin analogue SCI-57 by transient expression in Nicotiana benthamiana. Further work is being undertaken to evaluate the biological activity by glucose uptake by insulin-sensitive and insulin-resistant murine and human cultured adipocytes.Keywords: insulin analogue, mass spectrometry, Nicotiana benthamiana, transient expression
Procedia PDF Downloads 34846 Comparative Characteristics of Bacteriocins from Endemic Lactic Acid Bacteria
Authors: K. Karapetyan, F. Tkhruni, A. Aghajanyan, T. S. Balabekyan, L. Arstamyan
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Introduction: Globalization of the food supply has created the conditions favorable for the emergence and spread of food-borne and especially dangerous pathogens (EDP) in developing countries. The fresh-cut fruit and vegetable industry is searching for alternatives to replace chemical treatments with biopreservative approaches that ensure the safety of the processed foods product. Antimicrobial compounds of lactic acid bacteria (LAB) possess bactericidal or bacteriostatic activity against intestinal pathogens, spoilage organisms and food-borne pathogens such as Listeria monocytogenes, Staphylococcus aureus and Salmonella. Endemic strains of LAB were isolated. The strains, showing broad spectrum of antimicrobial activity against food spoiling microorganisms, were selected. The genotyping by 16S rRNA sequencing, GS-PCR, RAPD PCR methods showed that they were presented by Lactobacillus rhamnosus109, L.plantarum 65, L.plantarum 66 and Enterococcus faecium 64 species. LAB are deposited in "Microbial Depository Center" (MDC) SPC "Armbiotechnology". Methods: LAB strains were isolated from different dairy products from rural households from the highland regions of Armenia. Serially diluted samples were spread on MRS (Merck, Germany) and hydrolyzed milk agar (1,2 % w/v). Single colonies from each LAB were individually inoculated in liquid MRS medium and incubated at 37oC for 24 hours. Culture broth with biomass was centrifuged at 10,000 g during 20 min for obtaining of cell free culture broth (CFC). The antimicrobial substances from CFC broth were purified by the combination of adsorption-desorption and ion-exchange chromatography methods. Separation of bacteriocins was performed using a HPLC method on "Avex ODS" C18 column. Mass analysis of peptides recorded on the device API 4000 in the electron ionization mode. The spot-on-lawn method on the test culture plated in the solid medium was applied. The antimicrobial activity is expressed in arbitrary units (AU/ml). Results. Purification of CFC broth of LAB allowed to obtain partially purified antimicrobial preparations which contains bacteriocins with broad spectrum of antimicrobial activity. Investigation of their main biochemical properties shown, that inhibitory activity of preparations is partially reduced after treatment with proteinase K, trypsin, pepsin, suggesting a proteinaceous nature of bacteriocin-like substances containing in CFC broth. Preparations preserved their activity after heat treatment (50-121 oC, 20 min) and were stable in the pH range 3–8. The results of SDS PAAG electrophoresis show that L.plantarum 66 and Ent.faecium 64 strains have one bacteriocin (BCN) with maximal antimicrobial activity with approximate molecular weight 2.0-3.0 kDa. From L.rhamnosus 109 two BCNs were obtained. Mass spectral analysis indicates that these bacteriocins have peptide bonds and molecular weight of BCN 1 and BCN 2 are approximately 1.5 kDa and 700 Da. Discussion: Thus, our experimental data shown, that isolated endemic strains of LAB are able to produce bacteriocins with high and different inhibitory activity against broad spectrum of microorganisms of different taxonomic group, such as Salmonella sp., Esherichia coli, Bacillus sp., L.monocytogenes, Proteus mirabilis, Staph. aureus, Ps. aeruginosa. Obtained results proved the perspectives for use of endemic strains in the preservation of foodstuffs. Acknowledgments: This work was realized with financial support of the Project Global Initiatives for Preliferation Prevention (GIPP) T2- 298, ISTC A-1866.Keywords: antimicrobial activity, bacteriocins, endemic strains, food safety
Procedia PDF Downloads 561