Search results for: first principles study
1338 Mannose-Functionalized Lipopolysaccharide Nanoparticles for Macrophage-Targeted Dual Delivery of Rifampicin and Isoniazid
Authors: Mumuni Sumaila, Viness Pillay, Yahya E. Choonara, Pradeep Kumar, Pierre P. Kondiah
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Tuberculosis (TB) remains a serious challenge to public health globally, despite every effort put together to curb the disease. Current TB therapeutics available have proven to be inefficient due to a multitude of drawbacks that range from serious adverse effects/drug toxicity to inconsistent bioavailability, which ultimately contributes to the emergence of drug-resistant TB. An effective ‘cargo’ system designed to cleverly deliver therapeutic doses of anti-TB drugs to infection sites and in a sustained-release manner may provide a better therapeutic choice towards winning the war against TB. In the current study, we investigated mannose-functionalized lipopolysaccharide hybrid nanoparticles for safety and efficacy towards macrophage-targeted simultaneous delivery of the two first-line anti-TB drugs, rifampicin (RF) and isoniazid (IS). RF-IS-loaded lipopolysaccharide hybrid nanoparticles were fabricated using the solvent injection technique (SIT), incorporating soy lecithin (SL) and low molecular weight chitosan (CS) as the lipid and polysaccharide components, respectively. Surface-functionalized nanoparticles were obtained through the reaction of the aldehyde group of mannose with free amine functionality present at the surface of the nanoparticles. The functionalized nanocarriers were spherical with average particle size and surface charge of 107.83 nm and +21.77 mV, respectively, and entrapment efficiencies (EE) were 53.52% and 69.80% for RF and IS, respectively. FTIR spectrum revealed high-intensity bands between 1663 cm⁻¹ and 1408 cm⁻¹ wavenumbers (absent in non-functionalized nanoparticles), which could be attributed to the C=N stretching vibration produced by the formation of Schiff’s base (–N=CH–) during the mannosylation reaction. In vitro release studies showed a sustained-release profile for RF and IS, with less than half of the total payload released over a 48-hour period. The nanocarriers were biocompatible and safe, with more than 80% cell viability achieved when incubated with RAW 264.7 cells at concentrations 30 to 500 μg/mL over a 24-hour period. Cellular uptake studies (after a 24-hour incubation period with the murine macrophage cells, RAW 264.7) revealed a 13- and a 9-fold increase in intracellular accumulation of RF and IS, respectively, when compared with the unformulated RF+IS solution. A 6- and a 3-fold increase in intracellular accumulation of RF and IS, respectively, were observed when compared with the non-functionalized nanoparticles. Furthermore, fluorescent microscopy images showed nanoparticle internalization and accumulation within the RAW 264.7 cells, which was more significant in the mannose-functionalized system compared to the non-functionalized nanoparticles. The overall results suggested that the fabricated mannose-functionalized lipopolysaccharide nanoparticles are a safe and promising platform for macrophage-targeted delivery of anti-TB therapeutics. However, in vivo pharmacokinetic/pharmacodynamics studies are required to further substantiate the therapeutic efficacy of the nanosystem.Keywords: anti-tuberculosis therapeutics, hybrid nanosystem, lipopolysaccharide nanoparticles, macrophage-targeted delivery
Procedia PDF Downloads 1721337 DEKA-1 a Dose-Finding Phase 1 Trial: Observing Safety and Biomarkers using DK210 (EGFR) for Inoperable Locally Advanced and/or Metastatic EGFR+ Tumors with Progressive Disease Failing Systemic Therapy
Authors: Spira A., Marabelle A., Kientop D., Moser E., Mumm J.
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Background: Both interleukin-2 (IL-2) and interleukin-10 (IL-10) have been extensively studied for their stimulatory function on T cells and their potential to obtain sustainable tumor control in RCC, melanoma, lung, and pancreatic cancer as monotherapy, as well as combination with PD-1 blockers, radiation, and chemotherapy. While approved, IL-2 retains significant toxicity, preventing its widespread use. The significant efforts undertaken to uncouple IL-2 toxicity from its anti-tumor function have been unsuccessful, and early phase clinical safety observed with PEGylated IL-10 was not met in a blinded Phase 3 trial. Deka Biosciences has engineered a novel molecule coupling wild-type IL-2 to a high affinity variant of Epstein Barr Viral (EBV) IL-10 via a scaffold (scFv) that binds to epidermal growth factor receptors (EGFR). This patented molecule, termed DK210 (EGFR), is retained at high levels within the tumor microenvironment for days after dosing. In addition to overlapping and non-redundant anti-tumor function, IL-10 reduces IL-2 mediated cytokine release syndrome risks and inhibits IL-2 mediated T regulatory cell proliferation. Methods: DK210 (EGFR) is being evaluated in an open-label, dose-escalation (Phase 1) study with 5 (0.025-0.3 mg/kg) monotherapy dose levels and (expansion cohorts) in combination with PD-1 blockers, or radiation or chemotherapy in patients with advanced solid tumors overexpressing EGFR. Key eligibility criteria include 1) confirmed progressive disease on at least one line of systemic treatment, 2) EGFR overexpression or amplification documented in histology reports, 3) at least a 4 week or 5 half-lives window since last treatment, and 4) excluding subjects with long QT syndrome, multiple myeloma, multiple sclerosis, myasthenia gravis or uncontrolled infectious, psychiatric, neurologic, or cancer disease. Plasma and tissue samples will be investigated for pharmacodynamic and predictive biomarkers and genetic signatures associated with IFN-gamma secretion, aiming to select subjects for treatment in Phase 2. Conclusion: Through successful coupling of wild-type IL-2 with a high affinity IL-10 and targeting directly to the tumor microenvironment, DK210 (EGFR) has the potential to harness IL-2 and IL-10’s known anti-cancer promise while reducing immunogenicity and toxicity risks enabling safe concomitant cytokine treatment with other anti-cancer modalities.Keywords: cytokine, EGFR over expression, interleukine-2, interleukine-10, clinical trial
Procedia PDF Downloads 861336 Cytotoxic Effects of Ag/TiO2 Nanoparticles on the Unicellular Organism Paramecium tetraurelia
Authors: Juan Bernal-Martinez, Zoe Quinones-Jurado, Miguel Waldo-Mendoza, Elias Perez
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Introduction and Objective: Ag-TiO2 nanoparticles (NP) have been characterized as effective antibacterial compounds against E. aureous, E. coli, Salmonella and others. Because these nanoparticles have been used in plastic-food containers, there is a concern about the toxicity of Ag-TiO2 NP for higher organisms from protozoan, invertebrates, and mammals. The objective of this study is to evaluate the cytotoxic effect of Ag-TiO2 NP on the survival and swimming behavior of the unicellular organism Paramecium tetraurelia. Material and Methods: Preparation of metallic silver on TiO2 surface was based on chemical reduction route of AgNO3. Aqueous suspension of TiO2 nanoparticles was preparing by adding 5 g of TiO2 to 250 ml of deionized water and followed by sonication for 10 min. The required amount of AgNO3 solutions was added to TiO2 suspension, maintaining heating and stirring. Silver concentration was 0.5, 1.5, 5.0, 25, 35 and 45 % w/w versus TiO2. Paramecium tetraurelia (Carolina Biological, Cat. # 131560) was used as a biological preparation. It was cultured in artificial culture media made as follows: Stigmasterol 5 mg/ml of ethanol, Caseaminoacids 0.3 gr/lt.; KCl 4mM; CaCl2 1mM; MgCl2 100uM and MOPS 1mM, pH 7.3. This media was inoculated with Enterobacter-sp. Paramecium was concentrated after 24 hours of incubation by centrifugation. The pellet of cells was resuspended in 4.1.1 solution prepared as follows (in mM): KCl, 4 mM; CaCl2, 1mM and Trizma, 1mM; pH 7.3. Transmission electron microscopy (TEM) studies were performed to evaluate the appropriate dispersion and topographic distribution AgNPs deposited on TiO2. The experimental solutions were prepared as follows: 50 mg of Polyvinyhlpirolidone were added to 5 ml of 4.1.1. solution. Then, 50 mg of powder 25-Ag-TiO2 was added, mixing for 10 min and sonicated for 60 min. Survival of Paramecium and possible toxic effects after 25-Ag-TiO2 treatment was observed through an inverted microscope. The Paramecium swimming behavior and possible dead cells were recorded for periods of approximately 20-50 seconds by using a digital USB camera adapted to the microscope. Results and Discussion: TEM micrographs demonstrated the topographic distribution of AgNPs deposited on TiO2. 25Ag-TiO2 NP was efficiently dissolved and dispersed in 4.1.1 solution at concentrations from 0.1, 1 and 10 mg/ml. When Paramecium were treated with 25Ag-TiO2 NP at 100 ug/ml, it was observed that cells started swimming backwards. This backward swimming behavior is the typical avoiding reaction of the ciliate in response to a noxious stimulus. After 10 min of incubation, it was observed that Paramecium stopped swimming backwards and exploited. We can argue that this toxic effect of 25Ag-TiO2 NP is probably due to the calcium influx and calcium accumulation during the long-lasting swimming backwards. Conclusions: Here we have demonstrated that 25Ag-TiO2 NP has a specific toxic effect on an organism higher than bacteria such as the protozoan Paremecium. Probably these toxic phenomena could be expected to be observed in a higher organism such as invertebrates and mammals.Keywords: Ag-TiO2, calcium permeability, cytotoxicity, paramecium
Procedia PDF Downloads 2891335 Catalytic Alkylation of C2-C4 Hydrocarbons
Authors: Bolysbek Utelbayev, Tasmagambetova Aigerim, Toktasyn Raila, Markayev Yergali, Myrzakhanov Maxat
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Intensive development of secondary processes of destructive processing of crude oil has led to the occurrence of oil refining factories resources of C2-C4 hydrocarbons. Except for oil gases also contain basically C2-C4 hydrocarbon gases where some of the amounts are burned. All these data has induced interest to the study of producing alkylate from hydrocarbons С2-С4 which being as components of motor fuels. The purpose of this work was studying transformation propane-propene, butane-butene fractions at the presence of the ruthenium-chromic support catalyst whereas the carrier is served pillar - structural montmorillonite containing in native bentonite clay. In this work is considered condition and structure of the bentonite clay from the South-Kazakhstan area of the Republic Kazakhstan. For preparation rhodium support catalyst (0,5-1,0 mass. % Rh) was used chloride of rhodium-RhCl3∙3H2O, as a carrier was used modified bentonite clay. For modifying natural clay to pillar structural form were used polyhydroxy complexes of chromium. To aqueous solution of chloride chromium gradually flowed the solution of sodium hydroxide at gradual hashing up to pH~3-4. The concentration of chloride chromium was paid off proceeding from calculation 5-30 mmole Cr3+ per gram clay. Suspension bentonite (~1,0 mass. %) received by intensive washing it in water during 4 h, pH-water extract of clay makes -8-9. The acidity of environment supervised by means of digital pH meter OP-208/1. In order to prevent coagulation of a solution polyhydroxy complexes of chromium, it was slowly added to a suspension of clay. "Reserve of basicity" Cr3+:/OH-allowing to prevent coagulation chloride of rhodium made 1/3. After endurance processed suspensions of clay during 24 h, a deposit was washed by water and condensed. The sample, after separate from a liquid phase, dried at first at the room temperature, and then at 110°C (2h) with the subsequent rise the temperature up to 180°C (4h). After cooling the firm mass was pounded to a powder, it was shifted infractions with the certain sizes of particles. Fractions of particles modifying clay in the further were impregnated with an aqueous solution with rhodium-RhCl3∙3H2O (0,5-1,0 mаss % Rh ). Obtained pillar structural bentonite approaches heat resistance and its porous structure above the 773K. Pillar structural bentonite was used for preparation 1.0% Ru/Carrier (modifying bentonite) support catalysts where is realised alkylation of C2-C4 hydrocarbons. The process of alkylation is carried out at a partial pressure of hydrogen 0.5-1.0MPa. Outcome 2.2.4 three methyl pentane and 2.2.3 trimethylpentane achieved 40%. At alkylation butane-butene mixture outcome of the isooctane is achieved 60%. In this condition of studying the ethene is not undergoing to alkylation.Keywords: alkylation, butene, pillar structure, ruthenium catalyst
Procedia PDF Downloads 3961334 An Absolute Femtosecond Rangefinder for Metrological Support in Coordinate Measurements
Authors: Denis A. Sokolov, Andrey V. Mazurkevich
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In the modern world, there is an increasing demand for highly precise measurements in various fields, such as aircraft, shipbuilding, and rocket engineering. This has resulted in the development of appropriate measuring instruments that are capable of measuring the coordinates of objects within a range of up to 100 meters, with an accuracy of up to one micron. The calibration process for such optoelectronic measuring devices (trackers and total stations) involves comparing the measurement results from these devices to a reference measurement based on a linear or spatial basis. The reference used in such measurements could be a reference base or a reference range finder with the capability to measure angle increments (EDM). The base would serve as a set of reference points for this purpose. The concept of the EDM for replicating the unit of measurement has been implemented on a mobile platform, which allows for angular changes in the direction of laser radiation in two planes. To determine the distance to an object, a high-precision interferometer with its own design is employed. The laser radiation travels to the corner reflectors, which form a spatial reference with precisely known positions. When the femtosecond pulses from the reference arm and the measuring arm coincide, an interference signal is created, repeating at the frequency of the laser pulses. The distance between reference points determined by interference signals is calculated in accordance with recommendations from the International Bureau of Weights and Measures for the indirect measurement of time of light passage according to the definition of a meter. This distance is D/2 = c/2nF, approximately 2.5 meters, where c is the speed of light in a vacuum, n is the refractive index of a medium, and F is the frequency of femtosecond pulse repetition. The achieved uncertainty of type A measurement of the distance to reflectors 64 m (N•D/2, where N is an integer) away and spaced apart relative to each other at a distance of 1 m does not exceed 5 microns. The angular uncertainty is calculated theoretically since standard high-precision ring encoders will be used and are not a focus of research in this study. The Type B uncertainty components are not taken into account either, as the components that contribute most do not depend on the selected coordinate measuring method. This technology is being explored in the context of laboratory applications under controlled environmental conditions, where it is possible to achieve an advantage in terms of accuracy. In general, the EDM tests showed high accuracy, and theoretical calculations and experimental studies on an EDM prototype have shown that the uncertainty type A of distance measurements to reflectors can be less than 1 micrometer. The results of this research will be utilized to develop a highly accurate mobile absolute range finder designed for the calibration of high-precision laser trackers and laser rangefinders, as well as other equipment, using a 64 meter laboratory comparator as a reference.Keywords: femtosecond laser, pulse correlation, interferometer, laser absolute range finder, coordinate measurement
Procedia PDF Downloads 591333 A Machine Learning Approach for Assessment of Tremor: A Neurological Movement Disorder
Authors: Rajesh Ranjan, Marimuthu Palaniswami, A. A. Hashmi
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With the changing lifestyle and environment around us, the prevalence of the critical and incurable disease has proliferated. One such condition is the neurological disorder which is rampant among the old age population and is increasing at an unstoppable rate. Most of the neurological disorder patients suffer from some movement disorder affecting the movement of their body parts. Tremor is the most common movement disorder which is prevalent in such patients that infect the upper or lower limbs or both extremities. The tremor symptoms are commonly visible in Parkinson’s disease patient, and it can also be a pure tremor (essential tremor). The patients suffering from tremor face enormous trouble in performing the daily activity, and they always need a caretaker for assistance. In the clinics, the assessment of tremor is done through a manual clinical rating task such as Unified Parkinson’s disease rating scale which is time taking and cumbersome. Neurologists have also affirmed a challenge in differentiating a Parkinsonian tremor with the pure tremor which is essential in providing an accurate diagnosis. Therefore, there is a need to develop a monitoring and assistive tool for the tremor patient that keep on checking their health condition by coordinating them with the clinicians and caretakers for early diagnosis and assistance in performing the daily activity. In our research, we focus on developing a system for automatic classification of tremor which can accurately differentiate the pure tremor from the Parkinsonian tremor using a wearable accelerometer-based device, so that adequate diagnosis can be provided to the correct patient. In this research, a study was conducted in the neuro-clinic to assess the upper wrist movement of the patient suffering from Pure (Essential) tremor and Parkinsonian tremor using a wearable accelerometer-based device. Four tasks were designed in accordance with Unified Parkinson’s disease motor rating scale which is used to assess the rest, postural, intentional and action tremor in such patient. Various features such as time-frequency domain, wavelet-based and fast-Fourier transform based cross-correlation were extracted from the tri-axial signal which was used as input feature vector space for the different supervised and unsupervised learning tools for quantification of severity of tremor. A minimum covariance maximum correlation energy comparison index was also developed which was used as the input feature for various classification tools for distinguishing the PT and ET tremor types. An automatic system for efficient classification of tremor was developed using feature extraction methods, and superior performance was achieved using K-nearest neighbors and Support Vector Machine classifiers respectively.Keywords: machine learning approach for neurological disorder assessment, automatic classification of tremor types, feature extraction method for tremor classification, neurological movement disorder, parkinsonian tremor, essential tremor
Procedia PDF Downloads 1541332 Potential Impacts of Climate Change on Hydrological Droughts in the Limpopo River Basin
Authors: Nokwethaba Makhanya, Babatunde J. Abiodun, Piotr Wolski
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Climate change possibly intensifies hydrological droughts and reduces water availability in river basins. Despite this, most research on climate change effects in southern Africa has focused exclusively on meteorological droughts. This thesis projects the potential impact of climate change on the future characteristics of hydrological droughts in the Limpopo River Basin (LRB). The study uses regional climate model (RCM) measurements (from the Coordinated Regional Climate Downscaling Experiment, CORDEX) and a combination of hydrological simulations (using the Soil and Water Assessment Tool Plus model, SWAT+) to predict the impacts at four global warming levels (GWLs: 1.5℃, 2.0℃, 2.5℃, and 3.0℃) under the RCP8.5 future climate scenario. The SWAT+ model was calibrated and validated with a streamflow dataset observed over the basin, and the sensitivity of model parameters was investigated. The performance of the SWAT+LRB model was verified using the Nash-Sutcliffe efficiency (NSE), Percent Bias (PBIAS), Root Mean Square Error (RMSE), and coefficient of determination (R²). The Standardized Precipitation Evapotranspiration Index (SPEI) and the Standardized Precipitation Index (SPI) have been used to detect meteorological droughts. The Soil Water Index (SSI) has been used to define agricultural drought, while the Water Yield Drought Index (WYLDI), the Surface Run-off Index (SRI), and the Streamflow Index (SFI) have been used to characterise hydrological drought. The performance of the SWAT+ model simulations over LRB is sensitive to the parameters CN2 (initial SCS runoff curve number for moisture condition II) and ESCO (soil evaporation compensation factor). The best simulation generally performed better during the calibration period than the validation period. In calibration and validation periods, NSE is ≤ 0.8, while PBIAS is ≥ ﹣80.3%, RMSE ≥ 11.2 m³/s, and R² ≤ 0.9. The simulations project a future increase in temperature and potential evapotranspiration over the basin, but they do not project a significant future trend in precipitation and hydrological variables. However, the spatial distribution of precipitation reveals a projected increase in precipitation in the southern part of the basin and a decline in the northern part of the basin, with the region of reduced precipitation projected to increase with GWLs. A decrease in all hydrological variables is projected over most parts of the basin, especially over the eastern part of the basin. The simulations predict meteorological droughts (i.e., SPEI and SPI), agricultural droughts (i.e., SSI), and hydrological droughts (i.e., WYLDI, SRI) would become more intense and severe across the basin. SPEI-drought has a greater magnitude of increase than SPI-drought, and agricultural and hydrological droughts have a magnitude of increase between the two. As a result, this research suggests that future hydrological droughts over the LRB could be more severe than the SPI-drought projection predicts but less severe than the SPEI-drought projection. This research can be used to mitigate the effects of potential climate change on basin hydrological drought.Keywords: climate change, CORDEX, drought, hydrological modelling, Limpopo River Basin
Procedia PDF Downloads 1281331 Psychogeographic Analysis of Campus Design: Spatial Appropriation via Walking Practice in the Cases of Van Yüzüncü Yıl University and Ankara Middle East Technical University in Turkey
Authors: Yasemin İlkay
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Street is not only a crucial spatial unit in urban design and planning discipline but also the context of walking practice in urban space. Moreover, psychogeography concentrates on both ‘walking’ and, therefore, the differentiated forms of (urban) streets to examine the influence of the built environment on the feelings and attitudes of human beings. This paper focuses on ‘walking practice’ in university campuses with reference to spatial appropriation forms via a psychogeographic lens on the phenomenon of alle in two different cities of Turkey, Ankara, the capital city, and Van, in the eastern part of the country. Alle, as an extension of ‘street’ in university campuses, is the constructive spatial structure in university campuses, and as a result, it should be the (both physical and mental) spine of design policy while conceiving and constructing a university campus. The main question of the paper is: How does the interrelation of ‘campus design’ and ‘walking practice’ on alle penetrate reciprocally on the spatial representations of citizens within their urban daily lives. The body contacts with and at urban space (with other objects and subjects) via its movements and stops; this interaction occurs through the spatial pattern of occupancy and vacancy. Walking practice leads to a set of cognitive mental representations in relation to the repertoire of place attachment and spatial appropriation. University campuses are autonomous and fruitful urban spaces to investigate such an interaction. There are both physical/real and psychogeographic representations of the same urban spaces and urban spatial practices. This separation would indicate the invisible dimensions of the difference between ‘what is conceived’ and ‘what is perceived.’ This study aims to compare and contrast the role of alle in both campus design and spatial appropriation via walking at two differentiated university campuses by collecting the mental representations, doing in-depth interviews, and attending walks with the interviewees by psychogeographic techniques. Campus design and spatial appropriation will be compared [with reference to the conception and perception of alle] in three scales: (1) the historical spatial development stories and design approaches of university campuses, (2) the spatial pattern of campuses on the basis of alle, and (3) sub-behavioral regions of the alle in campuses in relation with mental representations and psychogeographic attentive walks. The sub-questions of the research are: [1] How and why do the design approaches differentiate in two university campuses in Turkey, [2] How the interrelation among alle design and spatial appropriation differs in these two cases, and [3] What do the differentiated gaps among real and psychographic maps indicate about the design and spatial appropriation interrelation. METU, as a well-designed, readable campus with its alle, promise a rich walking practice with in-depth and fruitful spatial appropriation regions; however, Van YYÜ limits both the practice and place attachment with its partial design with an alle which is later added to the campus. This research both displays the role of alle in the campus design, walking practice and spatial appropriation and opens a new methodological path to discover hidden knowledge within urban spaces.Keywords: alle, campus design, cognitive geography, psychogeography, spatial appropriation, Turkey
Procedia PDF Downloads 1051330 Effectiveness, Safety, and Tolerability Profile of Stribild® in HIV-1-infected Patients in the Clinical Setting
Authors: Heiko Jessen, Laura Tanus, Slobodan Ruzicic
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Objectives: The efficacy of Stribild®, an integrase strand transfer inhibitor (INSTI) -based STR, has been evaluated in randomized clinical trials and it has demonstrated durable capability in terms of achieving sustained suppression of HIV-1 RNA-levels. However, differences in monitoring frequency, existing selection bias and profile of patients enrolled in the trials, may all result in divergent efficacy of this regimen in routine clinical settings. The aim of this study was to assess the virologic outcomes, safety and tolerability profile of Stribild® in a routine clinical setting. Methods: This was a retrospective monocentric analysis on HIV-1-infected patients, who started with or were switched to Stribild®. Virological failure (VF) was defined as confirmed HIV-RNA>50 copies/ml. The minimum time of follow-up was 24 weeks. The percentage of patients remaining free of therapeutic failure was estimated using the time-to-loss-of-virologic-response (TLOVR) algorithm, by intent-to-treat analysis. Results: We analyzed the data of 197 patients (56 ART-naïve and 141 treatment-experienced patients), who fulfilled the inclusion criteria. Majority (95.9%) of patients were male. The median time of HIV-infection at baseline was 2 months in treatment-naïve and 70 months in treatment-experienced patients. Median time [IQR] under ART in treatment-experienced patients was 37 months. Among the treatment-experienced patients 27.0% had already been treated with a regimen consisting of two NRTIs and one INSTI, whereas 18.4% of them experienced a VF. The median time [IQR] of virological suppression prior to therapy with Stribild® in the treatment-experienced patients was 10 months [0-27]. At the end of follow-up (median 33 months), 87.3% (95% CI, 83.5-91.2) of treatment-naïve and 80.3% (95% CI, 75.8-84.8) of treatment-experienced patients remained free of therapeutic failure. Considering only treatment-experienced patients with baseline VL<50 copies/ml, 83.0% (95% CI, 78.5-87.5) remained free of therapeutic failure. A total of 17 patients stopped treatment with Stribild®, 5.4% (3/56) of them were treatment-naïve and 9.9% (14/141) were treatment-experienced patients. The Stribild® therapy was discontinued in 2 (1.0%) because of VF, loss to follow-up in 4 (2.0%), and drug-drug interactions in 2 (1.0%) patients. Adverse events were in 7 (3.6%) patients the reason to switch from therapy with Stribild® and further 2 (1.0%) patients decided personally to switch. The most frequently observed adverse events were gastrointestinal side effects (20.0%), headache (8%), rash events (7%) and dizziness (6%). In two patients we observed an emergence of novel resistances in integrase-gene. The N155H evolved in one patient and resulted in VF. In another patient S119R evolved either during or shortly upon switch from therapy with Stribild®. In one further patient with VF two novel mutations in the RT-gene were observed when compared to historical genotypic test result (V106I/M and M184V), whereby it is not clear whether they evolved during or already before the switch to Stribild®. Conclusions: Effectiveness of Stribild® for treatment-naïve patients was consistent with data obtained in clinical trials. The safety and tolerability profile as well as resistance development confirmed clinical efficacy of Stribild® in a daily practice setting.Keywords: ART, HIV, integrase inhibitor, stribild
Procedia PDF Downloads 2851329 Hydrological-Economic Modeling of Two Hydrographic Basins of the Coast of Peru
Authors: Julio Jesus Salazar, Manuel Andres Jesus De Lama
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There are very few models that serve to analyze the use of water in the socio-economic process. On the supply side, the joint use of groundwater has been considered in addition to the simple limits on the availability of surface water. In addition, we have worked on waterlogging and the effects on water quality (mainly salinity). In this paper, a 'complex' water economy is examined; one in which demands grow differentially not only within but also between sectors, and one in which there are limited opportunities to increase consumptive use. In particular, high-value growth, the growth of the production of irrigated crops of high value within the basins of the case study, together with the rapidly growing urban areas, provides a rich context to examine the general problem of water management at the basin level. At the same time, the long-term aridity of nature has made the eco-environment in the basins located on the coast of Peru very vulnerable, and the exploitation and immediate use of water resources have further deteriorated the situation. The presented methodology is the optimization with embedded simulation. The wide basin simulation of flow and water balances and crop growth are embedded with the optimization of water allocation, reservoir operation, and irrigation scheduling. The modeling framework is developed from a network of river basins that includes multiple nodes of origin (reservoirs, aquifers, water courses, etc.) and multiple demand sites along the river, including places of consumptive use for agricultural, municipal and industrial, and uses of running water on the coast of Peru. The economic benefits associated with water use are evaluated for different demand management instruments, including water rights, based on the production and benefit functions of water use in the urban agricultural and industrial sectors. This work represents a new effort to analyze the use of water at the regional level and to evaluate the modernization of the integrated management of water resources and socio-economic territorial development in Peru. It will also allow the establishment of policies to improve the process of implementation of the integrated management and development of water resources. The input-output analysis is essential to present a theory about the production process, which is based on a particular type of production function. Also, this work presents the Computable General Equilibrium (CGE) version of the economic model for water resource policy analysis, which was specifically designed for analyzing large-scale water management. As to the platform for CGE simulation, GEMPACK, a flexible system for solving CGE models, is used for formulating and solving CGE model through the percentage-change approach. GEMPACK automates the process of translating the model specification into a model solution program.Keywords: water economy, simulation, modeling, integration
Procedia PDF Downloads 1551328 Continuous and Discontinuos Modeling of Wellbore Instability in Anisotropic Rocks
Authors: C. Deangeli, P. Obentaku Obenebot, O. Omwanghe
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The study focuses on the analysis of wellbore instability in rock masses affected by weakness planes. The occurrence of failure in such a type of rocks can occur in the rock matrix and/ or along the weakness planes, in relation to the mud weight gradient. In this case the simple Kirsch solution coupled with a failure criterion cannot supply a suitable scenario for borehole instabilities. Two different numerical approaches have been used in order to investigate the onset of local failure at the wall of a borehole. For each type of approach the influence of the inclination of weakness planes has been investigates, by considering joint sets at 0°, 35° and 90° to the horizontal. The first set of models have been carried out with FLAC 2D (Fast Lagrangian Analysis of Continua) by considering the rock material as a continuous medium, with a Mohr Coulomb criterion for the rock matrix and using the ubiquitous joint model for accounting for the presence of the weakness planes. In this model yield may occur in either the solid or along the weak plane, or both, depending on the stress state, the orientation of the weak plane and the material properties of the solid and weak plane. The second set of models have been performed with PFC2D (Particle Flow code). This code is based on the Discrete Element Method and considers the rock material as an assembly of grains bonded by cement-like materials, and pore spaces. The presence of weakness planes is simulated by the degradation of the bonds between grains along given directions. In general the results of the two approaches are in agreement. However the discrete approach seems to capture more complex phenomena related to local failure in the form of grain detachment at wall of the borehole. In fact the presence of weakness planes in the discontinuous medium leads to local instability along the weak planes also in conditions not predicted from the continuous solution. In general slip failure locations and directions do not follow the conventional wellbore breakout direction but depend upon the internal friction angle and the orientation of the bedding planes. When weakness plane is at 0° and 90° the behaviour are similar to that of a continuous rock material, but borehole instability is more severe when weakness planes are inclined at an angle between 0° and 90° to the horizontal. In conclusion, the results of the numerical simulations show that the prediction of local failure at the wall of the wellbore cannot disregard the presence of weakness planes and consequently the higher mud weight required for stability for any specific inclination of the joints. Despite the discrete approach can simulate smaller areas because of the large number of particles required for the generation of the rock material, however it seems to investigate more correctly the occurrence of failure at the miscroscale and eventually the propagation of the failed zone to a large portion of rock around the wellbore.Keywords: continuous- discontinuous, numerical modelling, weakness planes wellbore, FLAC 2D
Procedia PDF Downloads 4991327 The Role of Macroeconomic Condition and Volatility in Credit Risk: An Empirical Analysis of Credit Default Swap Index Spread on Structural Models in U.S. Market during Post-Crisis Period
Authors: Xu Wang
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This research builds linear regressions of U.S. macroeconomic condition and volatility measures in the investment grade and high yield Credit Default Swap index spreads using monthly data from March 2009 to July 2016, to study the relationship between different dimensions of macroeconomy and overall credit risk quality. The most significant contribution of this research is systematically examining individual and joint effects of macroeconomic condition and volatility on CDX spreads by including macroeconomic time series that captures different dimensions of the U.S. economy. The industrial production index growth, non-farm payroll growth, consumer price index growth, 3-month treasury rate and consumer sentiment are introduced to capture the condition of real economic activity, employment, inflation, monetary policy and risk aversion respectively. The conditional variance of the macroeconomic series is constructed using ARMA-GARCH model and is used to measure macroeconomic volatility. The linear regression model is conducted to capture relationships between monthly average CDX spreads and macroeconomic variables. The Newey–West estimator is used to control for autocorrelation and heteroskedasticity in error terms. Furthermore, the sensitivity factor analysis and standardized coefficients analysis are conducted to compare the sensitivity of CDX spreads to different macroeconomic variables and to compare relative effects of macroeconomic condition versus macroeconomic uncertainty respectively. This research shows that macroeconomic condition can have a negative effect on CDX spread while macroeconomic volatility has a positive effect on determining CDX spread. Macroeconomic condition and volatility variables can jointly explain more than 70% of the whole variation of the CDX spread. In addition, sensitivity factor analysis shows that the CDX spread is the most sensitive to Consumer Sentiment index. Finally, the standardized coefficients analysis shows that both macroeconomic condition and volatility variables are important in determining CDX spread but macroeconomic condition category of variables have more relative importance in determining CDX spread than macroeconomic volatility category of variables. This research shows that the CDX spread can reflect the individual and joint effects of macroeconomic condition and volatility, which suggests that individual investors or government should carefully regard CDX spread as a measure of overall credit risk because the CDX spread is influenced by macroeconomy. In addition, the significance of macroeconomic condition and volatility variables, such as Non-farm Payroll growth rate and Industrial Production Index growth volatility suggests that the government, should pay more attention to the overall credit quality in the market when macroecnomy is low or volatile.Keywords: autoregressive moving average model, credit spread puzzle, credit default swap spread, generalized autoregressive conditional heteroskedasticity model, macroeconomic conditions, macroeconomic uncertainty
Procedia PDF Downloads 1671326 Quality by Design in the Optimization of a Fast HPLC Method for Quantification of Hydroxychloroquine Sulfate
Authors: Pedro J. Rolim-Neto, Leslie R. M. Ferraz, Fabiana L. A. Santos, Pablo A. Ferreira, Ricardo T. L. Maia-Jr., Magaly A. M. Lyra, Danilo A F. Fonte, Salvana P. M. Costa, Amanda C. Q. M. Vieira, Larissa A. Rolim
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Initially developed as an antimalarial agent, hydroxychloroquine (HCQ) sulfate is often used as a slow-acting antirheumatic drug in the treatment of disorders of connective tissue. The United States Pharmacopeia (USP) 37 provides a reversed-phase HPLC method for quantification of HCQ. However, this method was not reproducible, producing asymmetric peaks in a long analysis time. The asymmetry of the peak may cause an incorrect calculation of the concentration of the sample. Furthermore, the analysis time is unacceptable, especially regarding the routine of a pharmaceutical industry. The aiming of this study was to develop a fast, easy and efficient method for quantification of HCQ sulfate by High Performance Liquid Chromatography (HPLC) based on the Quality by Design (QbD) methodology. This method was optimized in terms of peak symmetry using the surface area graphic as the Design of Experiments (DoE) and the tailing factor (TF) as an indicator to the Design Space (DS). The reference method used was that described at USP 37 to the quantification of the drug. For the optimized method, was proposed a 33 factorial design, based on the QbD concepts. The DS was created with the TF (in a range between 0.98 and 1.2) in order to demonstrate the ideal analytical conditions. Changes were made in the composition of the USP mobile-phase (USP-MP): USP-MP: Methanol (90:10 v/v, 80:20 v/v and 70:30 v/v), in the flow (0.8, 1.0 and 1.2 mL) and in the oven temperature (30, 35, and 40ºC). The USP method allowed the quantification of drug in a long time (40-50 minutes). In addition, the method uses a high flow rate (1,5 mL.min-1) which increases the consumption of expensive solvents HPLC grade. The main problem observed was the TF value (1,8) that would be accepted if the drug was not a racemic mixture, since the co-elution of the isomers can become an unreliable peak integration. Therefore, the optimization was suggested in order to reduce the analysis time, aiming a better peak resolution and TF. For the optimization method, by the analysis of the surface-response plot it was possible to confirm the ideal setting analytical condition: 45 °C, 0,8 mL.min-1 and 80:20 USP-MP: Methanol. The optimized HPLC method enabled the quantification of HCQ sulfate, with a peak of high resolution, showing a TF value of 1,17. This promotes good co-elution of isomers of the HCQ, ensuring an accurate quantification of the raw material as racemic mixture. This method also proved to be 18 times faster, approximately, compared to the reference method, using a lower flow rate, reducing even more the consumption of the solvents and, consequently, the analysis cost. Thus, an analytical method for the quantification of HCQ sulfate was optimized using QbD methodology. This method proved to be faster and more efficient than the USP method, regarding the retention time and, especially, the peak resolution. The higher resolution in the chromatogram peaks supports the implementation of the method for quantification of the drug as racemic mixture, not requiring the separation of isomers.Keywords: analytical method, hydroxychloroquine sulfate, quality by design, surface area graphic
Procedia PDF Downloads 6391325 Real-Time Monitoring of Complex Multiphase Behavior in a High Pressure and High Temperature Microfluidic Chip
Authors: Renée M. Ripken, Johannes G. E. Gardeniers, Séverine Le Gac
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Controlling the multiphase behavior of aqueous biomass mixtures is essential when working in the biomass conversion industry. Here, the vapor/liquid equilibria (VLE) of ethylene glycol, glycerol, and xylitol were studied for temperatures between 25 and 200 °C and pressures of 1 to 10 bar. These experiments were performed in a microfluidic platform, which exhibits excellent heat transfer properties so that equilibrium is reached fast. Firstly, the saturated vapor pressure as a function of the temperature and the substrate mole fraction of the substrate was calculated using AspenPlus with a Redlich-Kwong-Soave Boston-Mathias (RKS-BM) model. Secondly, we developed a high-pressure and high-temperature microfluidic set-up for experimental validation. Furthermore, we have studied the multiphase flow pattern that occurs after the saturation temperature was achieved. A glass-silicon microfluidic device containing a 0.4 or 0.2 m long meandering channel with a depth of 250 μm and a width of 250 or 500 μm was fabricated using standard microfabrication techniques. This device was placed in a dedicated chip-holder, which includes a ceramic heater on the silicon side. The temperature was controlled and monitored by three K-type thermocouples: two were located between the heater and the silicon substrate, one to set the temperature and one to measure it, and the third one was placed in a 300 μm wide and 450 μm deep groove on the glass side to determine the heat loss over the silicon. An adjustable back pressure regulator and a pressure meter were added to control and evaluate the pressure during the experiment. Aqueous biomass solutions (10 wt%) were pumped at a flow rate of 10 μL/min using a syringe pump, and the temperature was slowly increased until the theoretical saturation temperature for the pre-set pressure was reached. First and surprisingly, a significant difference was observed between our theoretical saturation temperature and the experimental results. The experimental values were 10’s of degrees higher than the calculated ones and, in some cases, saturation could not be achieved. This discrepancy can be explained in different ways. Firstly, the pressure in the microchannel is locally higher due to both the thermal expansion of the liquid and the Laplace pressure that has to be overcome before a gas bubble can be formed. Secondly, superheating effects are likely to be present. Next, once saturation was reached, the flow pattern of the gas/liquid multiphase system was recorded. In our device, the point of nucleation can be controlled by taking advantage of the pressure drop across the channel and the accurate control of the temperature. Specifically, a higher temperature resulted in nucleation further upstream in the channel. As the void fraction increases downstream, the flow regime changes along the channel from bubbly flow to Taylor flow and later to annular flow. All three flow regimes were observed simultaneously. The findings of this study are key for the development and optimization of a microreactor for hydrogen production from biomass.Keywords: biomass conversion, high pressure and high temperature microfluidics, multiphase, phase diagrams, superheating
Procedia PDF Downloads 2171324 Clinical Manifestations, Pathogenesis and Medical Treatment of Stroke Caused by Basic Mitochondrial Abnormalities (Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like Episodes, MELAS)
Authors: Wu Liching
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Aim This case aims to discuss the pathogenesis, clinical manifestations and medical treatment of strokes caused by mitochondrial gene mutations. Methods Diagnosis of ischemic stroke caused by mitochondrial gene defect by means of "next-generation sequencing mitochondrial DNA gene variation detection", imaging examination, neurological examination, and medical history; this study took samples from the neurology ward of a medical center in northern Taiwan cases diagnosed with acute cerebral infarction as the research objects. Result This case is a 49-year-old married woman with a rare disease, mitochondrial gene mutation inducing ischemic stroke. She has severe hearing impairment and needs to use hearing aids, and has a history of diabetes. During the patient’s hospitalization, the blood test showed that serum Lactate: 7.72 mmol/L, Lactate (CSF) 5.9 mmol/L. Through the collection of relevant medical history, neurological evaluation showed changes in consciousness and cognition, slow response in language expression, and brain magnetic resonance imaging examination showed subacute bilateral temporal lobe infarction, which was an atypical type of stroke. The lineage DNA gene has m.3243A>G known pathogenic mutation point, and its heteroplasmic level is 24.6%. This pathogenic point is located in MITOMAP and recorded as Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like episodes (MELAS) , Leigh Syndrome and other disease-related pathogenic loci, this mutation is located in ClinVar and recorded as Pathogenic (dbSNP: rs199474657), so it is diagnosed as a case of stroke caused by a rare disease mitochondrial gene mutation. After medical treatment, there was no more seizure during hospitalization. After interventional rehabilitation, the patient's limb weakness, poor language function, and cognitive impairment have all improved significantly. Conclusion Mitochondrial disorders can also be associated with abnormalities in psychological, neurological, cerebral cortical function, and autonomic functions, as well as problems with internal medical diseases. Therefore, the differential diagnoses cover a wide range and are not easy to be diagnosed. After neurological evaluation, medical history collection, imaging and rare disease serological examination, atypical ischemic stroke caused by rare mitochondrial gene mutation was diagnosed. We hope that through this case, the diagnosis of rare disease mitochondrial gene variation leading to cerebral infarction will be more familiar to clinical medical staff, and this case report may help to improve the clinical diagnosis and treatment for patients with similar clinical symptoms in the future.Keywords: acute stroke, MELAS, lactic acidosis, mitochondrial disorders
Procedia PDF Downloads 701323 Collaborative Management Approach for Logistics Flow Management of Cuban Medicine Supply Chain
Authors: Ana Julia Acevedo Urquiaga, Jose A. Acevedo Suarez, Ana Julia Urquiaga Rodriguez, Neyfe Sablon Cossio
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Despite the progress made in logistics and supply chains fields, it is unavoidable the development of business models that use efficiently information to facilitate the integrated logistics flows management between partners. Collaborative management is an important tool for materializing the cooperation between companies, as a way to achieve the supply chain efficiency and effectiveness. The first face of this research was a comprehensive analysis of the collaborative planning on the Cuban companies. It is evident that they have difficulties in supply chains planning where production, supplies and replenishment planning are independent tasks, as well as logistics and distribution operations. Large inventories generate serious financial and organizational problems for entities, demanding increasing levels of working capital that cannot be financed. Problems were found in the efficient application of Information and Communication Technology on business management. The general objective of this work is to develop a methodology that allows the deployment of a planning and control system in a coordinated way on the medicine’s logistics system in Cuba. To achieve these objectives, several mechanisms of supply chain coordination, mathematical programming models, and other management techniques were analyzed to meet the requirements of collaborative logistics management in Cuba. One of the findings is the practical and theoretical inadequacies of the studied models to solve the current situation of the Cuban logistics systems management. To contribute to the tactical-operative management of logistics, the Collaborative Logistics Flow Management Model (CLFMM) is proposed as a tool for the balance of cycles, capacities, and inventories, always to meet the final customers’ demands in correspondence with the service level expected by these. The CLFMM has as center the supply chain planning and control system as a unique information system, which acts on the processes network. The development of the model is based on the empirical methods of analysis-synthesis and the study cases. Other finding is the demonstration of the use of a single information system to support the supply chain logistics management, allows determining the deadlines and quantities required in each process. This ensures that medications are always available to patients and there are no faults that put the population's health at risk. The simulation of planning and control with the CLFMM in medicines such as dipyrone and chlordiazepoxide, during 5 months of 2017, permitted to take measures to adjust the logistic flow, eliminate delayed processes and avoid shortages of the medicines studied. As a result, the logistics cycle efficiency can be increased to 91%, the inventory rotation would increase, and this results in a release of financial resources.Keywords: collaborative management, medicine logistic system, supply chain planning, tactical-operative planning
Procedia PDF Downloads 1761322 Generating Ideas to Improve Road Intersections Using Design with Intent Approach
Authors: Omar Faruqe Hamim, M. Shamsul Hoque, Rich C. McIlroy, Katherine L. Plant, Neville A. Stanton
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Road safety has become an alarming issue, especially in low-middle income developing countries. The traditional approaches lack the out of the box thinking, making engineers confined to applying usual techniques in making roads safer. A socio-technical approach has recently been introduced in improving road intersections through designing with intent. This Design With Intent (DWI) approach aims to give practitioners a more nuanced approach to design and behavior, working with people, people’s understanding, and the complexities of everyday human experience. It's a collection of design patterns —and a design and research approach— for exploring the interactions between design and people’s behavior across products, services, and environments, both digital and physical. Through this approach, it can be seen that how designing with people in behavior change can be applied to social and environmental problems, as well as commercially. It has a total of 101 cards across eight different lenses, such as architectural, error-proofing, interaction, ludic, perceptual, cognitive, Machiavellian, and security lens each having its own distinct characteristics of extracting ideas from the participant of this approach. For this research purpose, a three-legged accident blackspot intersection of a national highway has been chosen to perform the DWI workshop. Participants from varying fields such as civil engineering, naval architecture and marine engineering, urban and regional planning, and sociology actively participated for a day long workshop. While going through the workshops, the participants were given a preamble of the accident scenario and a brief overview of DWI approach. Design cards of varying lenses were distributed among 10 participants and given an hour and a half for brainstorming and generating ideas to improve the safety of the selected intersection. After the brainstorming session, the participants spontaneously went through roundtable discussions regarding the ideas they have come up with. According to consensus of the forum, ideas were accepted or rejected. These generated ideas were then synthesized and agglomerated to bring about an improvement scheme for the intersection selected in our study. To summarize the improvement ideas from DWI approach, color coding of traffic lanes for separate vehicles, channelizing the existing bare intersection, providing advance warning traffic signs, cautionary signs and educational signs motivating road users to drive safe, using textured surfaces at approach with rumble strips before the approach of intersection were the most significant one. The motive of this approach is to bring about new ideas from the road users and not just depend on traditional schemes to increase the efficiency, safety of roads as well and to ensure the compliance of road users since these features are being generated from the minds of users themselves.Keywords: design with intent, road safety, human experience, behavior
Procedia PDF Downloads 1401321 Midwives’ Perceptions and Experiences of Recommending and Delivering Vaccines to Pregnant Women Following the COVID-19 Pandemic
Authors: Cath Grimley, Debra Bick, Sarah Hillman, Louise Clarke, Helen Atherton, Jo Parsons
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The problem: Women in the UK are offered influenza (flu), pertussis (whooping cough) and COVID-19 vaccinations during their pregnancy but uptake of all three vaccines is below the desired rate. These vaccines are offered during pregnancy as pregnant women are at an increased risk of hospitalisation, morbidity, and mortality from these illnesses. Exposure to these diseases during pregnancy can also have a negative impact on the unborn baby with an increased risk of serious complications both while in utero and following birth. The research aims to explore perceptions about the vaccinations offered in pregnancy both from the perspectives of pregnant women and midwives. To determine factors that influence pregnant women’s decisions about whether or not to accept the vaccines following the Covid-19 pandemic and to explore midwives’ experiences of recommending and delivering vaccines. The approach: This research follows a qualitative design involving semi-structured interviews with pregnant women and midwives in the UK. Interviews with midwives explored vaccination discussions they routinely have with pregnant women and identified some of the barriers to vaccination that pregnant women discuss with them. Interviews with pregnant women explored their views since the COVID-19 pandemic about vaccinations offered during pregnancy, and whether the pandemic has influenced perceptions of vulnerability to illness in pregnant women. Midwives were recruited via participating hospitals and midwife specific social media groups. Pregnant women were recruited via participating hospitals and community groups. All interviews were conducted remotely (using telephone or Microsoft Teams) and analysed using thematic analysis. Findings: 43 pregnant women and 16 midwives were recruited and interviewed. The findings presented here will focus on data from midwives. Topics identified included three key themes for midwives. These were 1) Delivery of vaccinations which includes the convenience of offering vaccinations while attending standard antenatal appointments and practical barriers faced in delivering these vaccinations at hospital. 2) Messages and guidance included the importance of up-to-date informational needs for midwives to deliver vaccines and that uncertainty and conflicting messages about the COVID-19 vaccine during pregnancy were a barrier to delivery. 3) Recommendations to have vaccines look at all aspects of recommendations such as how recommendations are communicated, the contents of the recommendation, the importance of the vaccine and the impact of those recommendations on whether women accept the vaccine. Implications: Findings highlight the importance for midwives to receive clear and consistent information so they can feel confident in relaying this information while recommending and delivering vaccines to pregnant women. Emphasising why vaccines are important when recommending vaccinations to pregnant women in addition to standard information on the availability and timing will add to the strength and impact of that recommendation in helping women to make informed decisions about accepting vaccines. The findings of this study will inform the development of an intervention to increase vaccination uptake amongst pregnant women.Keywords: vaccination, pregnancy, qualitative, interviews, Covid-19, midwives
Procedia PDF Downloads 981320 Magnetron Sputtered Thin-Film Catalysts with Low Noble Metal Content for Proton Exchange Membrane Water Electrolysis
Authors: Peter Kus, Anna Ostroverkh, Yurii Yakovlev, Yevheniia Lobko, Roman Fiala, Ivan Khalakhan, Vladimir Matolin
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Hydrogen economy is a concept of low-emission society which harvests most of its energy from renewable sources (e.g., wind and solar) and in case of overproduction, electrochemically turns the excess amount into hydrogen, which serves as an energy carrier. Proton exchange membrane water electrolyzers (PEMWE) are the backbone of this concept. By fast-response electricity to hydrogen conversion, the PEMWEs will not only stabilize the electrical grid but also provide high-purity hydrogen for variety of fuel cell powered devices, ranging from consumer electronics to vehicles. Wider commercialization of PEMWE technology is however hindered by high prices of noble metals which are necessary for catalyzing the redox reactions within the cell. Namely, platinum for hydrogen evolution reaction (HER), running on cathode, and iridium for oxygen evolution reaction (OER) on anode. Possible way of how to lower the loading of Pt and Ir is by using conductive high-surface nanostructures as catalyst supports in conjunction with thin-film catalyst deposition. The presented study discusses unconventional technique of membrane electron assembly (MEA) preparation. Noble metal catalysts (Pt and Ir) were magnetron sputtered in very low loadings onto the surface of porous sublayers (located on gas diffusion layer or directly on membrane), forming so to say localized three-phase boundary. Ultrasonically sprayed corrosion resistant TiC-based sublayer was used as a support material on anode, whereas magnetron sputtered nanostructured etched nitrogenated carbon (CNx) served the same role on cathode. By using this configuration, we were able to significantly decrease the amount of noble metals (to thickness of just tens of nanometers), while keeping the performance comparable to that of average state-of-the-art catalysts. Complex characterization of prepared supported catalysts includes in-cell performance and durability tests, electrochemical impedance spectroscopy (EIS) as well as scanning electron microscopy (SEM) imaging and X-ray photoelectron spectroscopy (XPS) analysis. Our research proves that magnetron sputtering is a suitable method for thin-film deposition of electrocatalysts. Tested set-up of thin-film supported anode and cathode catalysts with combined loading of just 120 ug.cm⁻² yields remarkable values of specific current. Described approach of thin-film low-loading catalyst deposition might be relevant when noble metal reduction is the topmost priority.Keywords: hydrogen economy, low-loading catalyst, magnetron sputtering, proton exchange membrane water electrolyzer
Procedia PDF Downloads 1631319 Impact of National Institutions on Corporate Social Performance
Authors: Debdatta Mukherjee, Abhiman Das, Amit Garg
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In recent years, there is a growing interest about corporate social responsibility of firms in both academic literature and business world. Since business forms a part of society incorporating socio-environment concerns into its value chain, activities are vital for ensuring mutual sustainability and prosperity. But, until now most of the works have been either descriptive or normative rather than positivist in tone. Even the few ones with a positivist approach have mostly studied the link between corporate financial performance and corporate social performance. However, these studies have been severely criticized by many eminent authors on grounds that they lack a theoretical basis for their findings. They have also argued that apart from corporate financial performance, there must be certain other crucial influences that are likely to determine corporate social performance of firms. In fact, several studies have indicated that firms operating in distinct national institutions show significant variations in the corporate social responsibility practices that they undertake. This clearly suggests that the institutional context of a country in which the firms operate is a key determinant of corporate social performance of firms. Therefore, this paper uses an institutional framework to understand why corporate social performance of firms vary across countries. It examines the impact of country level institutions on corporate social performance using a sample of 3240 global publicly-held firms across 33 countries covering the period 2010-2015. The country level institutions include public institutions, private institutions, markets and capacity to innovate. Econometric Analysis has been mainly used to assess this impact. A three way panel data analysis using fixed effects has been used to test and validate appropriate hypotheses. Most of the empirical findings confirm our hypotheses and the economic significance indicates the specific impact of each variable and their importance relative to others. The results suggest that institutional determinants like ethical behavior of private institutions, goods market, labor market and innovation capacity of a country are significantly related to the corporate social performance of firms. Based on our findings, few implications for policy makers from across the world have also been suggested. The institutions in a country should promote competition. The government should use policy levers for upgrading home demands, like setting challenging yet flexible safety, quality and environment standards, and framing policies governing buyer information, providing innovative recourses to low quality goods and services and promoting early adoption of new and technologically advanced products. Moreover, the institution building in a country should be such that they facilitate and improve the capacity of firms to innovate. Therefore, the proposed study argues that country level institutions impact corporate social performance of firms, empirically validates the same, suggest policy implications and attempts to contribute to an extended understanding of corporate social responsibility and corporate social performance in a multinational context.Keywords: corporate social performance, corporate social responsibility, institutions, markets
Procedia PDF Downloads 1661318 Genetically Modified Fuel-Ethanol Industrial Yeast Strains as Biocontrol Agents
Authors: Patrícia Branco, Catarina Prista, Helena Albergaria
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Industrial fuel-ethanol fermentations are carried out under non-sterile conditions, which favors the development of microbial contaminants, leading to huge economic losses. Wild yeasts such as Brettanomyces bruxellensis and lactic acid bacteria are the main contaminants of industrial bioethanol fermentation, affecting Saccharomyces cerevisiae performance and decreasing ethanol yields and productivity. In order to control microbial contaminations, the fuel-ethanol industry uses different treatments, including acid washing and antibiotics. However, these control measures carry environmental risks such as acid toxicity and the rise of antibiotic-resistant bacteria. Therefore, it is crucial to develop and apply less toxic and more environmentally friendly biocontrol methods. In the present study, an industrial fuel-ethanol starter, S. cerevisiae Ethanol-Red, was genetically modified to over-express AMPs with activity against fuel-ethanol microbial contaminants and evaluated regarding its biocontrol effect during mixed-culture alcoholic fermentations artificially contaminated with B. bruxellensis. To achieve this goal, S. cerevisiae Ethanol-Red strain was transformed with a plasmid containing the AMPs-codifying genes, i.e., partial sequences of TDH1 (925-963 bp) and TDH2/3 (925-963 bp) and a geneticin resistance marker. The biocontrol effect of those genetically modified strains was evaluated against B. bruxellensis and compared with the antagonistic effect exerted by the modified strain with an empty plasmid (without the AMPs-codifying genes) and the non-modified strain S. cerevisiae Ethanol-Red. For that purpose, mixed-culture alcoholic fermentations were performed in a synthetic must use the modified S. cerevisiae Ethanol-Red strains together with B. bruxellensis. Single-culture fermentations of B. bruxellensis strains were also performed as a negative control of the antagonistic effect exerted by S. cerevisiae strains. Results clearly showed an improved biocontrol effect of the genetically-modified strains against B. bruxellensis when compared with the modified Ethanol-Red strain with the empty plasmid (without the AMPs-codifying genes) and with the non-modified Ethanol-Red strain. In mixed-culture fermentation with the modified S. cerevisiae strain, B. bruxellensis culturability decreased from 5×104 CFU/mL on day-0 to less than 1 CFU/mL on day-10, while in single-culture B. bruxellensis increased its culturability from 6×104 to 1×106 CFU/mL in the first 6 days and kept this value until day-10. Besides, the modified Ethanol-Red strain exhibited an enhanced antagonistic effect against B. bruxellensis when compared with that induced by the non-modified Ethanol-Red strain. Indeed, culturability loss of B. bruxellensis after 10 days of fermentation with the modified Ethanol-Red strain was 98.7 and 100% higher than that occurred in fermentations performed with the non-modified Ethanol-Red and the empty-plasmid modified strain, respectively. Therefore, one can conclude that the S. cerevisiae genetically modified strain obtained in the present work may be a valuable solution for the mitigation of microbial contamination in fuel-ethanol fermentations, representing a much safer and environmentally friendly preservation strategy than the antimicrobial treatments (acid washing and antibiotics) currently applied in fuel-ethanol industry.Keywords: antimicrobial peptides, fuel-ethanol microbial contaminations, fuel-ethanol fermentation, biocontrol agents, genetically-modified yeasts
Procedia PDF Downloads 991317 Determinants of Walking among Middle-Aged and Older Overweight and Obese Adults: Demographic, Health, and Socio-Environmental Factors
Authors: Samuel N. Forjuoh, Marcia G. Ory, Jaewoong Won, Samuel D. Towne, Suojin Wang, Chanam Lee
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The public health burden of obesity is well established as is the influence of physical activity (PA) on the health and wellness of individuals who are obese. This study examined the influence of selected demographic, health, and socioenvironmental factors on the walking behaviors of middle-aged and older overweight and obese adults. Online and paper surveys were administered to community-dwelling overweight and obese adults aged ≥ 50 years residing in four cities in central Texas and seen by a family physician in the primary care clinic from October 2013 to June 2014. Descriptive statistics were used to characterize participants’ anthropometric and demographic data as well as their health conditions and walking, socioenvironmental, and more broadly defined PA behaviors. Then Pearson chi-square tests were used to assess differences between participants who reported walking the recommended ≥ 150 minutes for any purpose in a typical week as a proxy to meeting the U.S. Centers for Disease Control and Prevention’s PA guidelines and those who did not. Finally, logistic regression was used to predict walking the recommended ≥ 150 minutes for any purpose, controlling for covariates. The analysis was conducted in 2016. Of the total sample (n=253, survey response rate of 6.8%), the majority were non-Hispanic white (81.7%), married (74.5%), male (53.5%), and reported an annual household income of ≥ $50,000 (65.7%). Approximately, half were employed (49.6%), or had at least a college degree (51.8%). Slightly more than 1 in 5 (n=57, 22.5%) reported walking the recommended ≥150 minutes for any purpose in a typical week. The strongest predictors of walking the recommended ≥ 150 minutes for any purpose in a typical week in adjusted analysis were related to education and a high favorable perception of the neighborhood environment. Compared to those with a high school diploma or some college, participants with at least a college degree were five times as likely to walk the recommended ≥ 150 minutes for any purpose (OR=5.55, 95% CI=1.79-17.25). Walking the recommended ≥ 150 minutes for any purpose was significantly associated with participants who disagreed that there were many distracted drivers (e.g., on the cell phone while driving) in their neighborhood (OR=4.08, 95% CI=1.47-11.36) and those who agreed that there are sidewalks or protected walkways (e.g., walking trails) in their neighborhood (OR=3.55, 95% CI=1.10-11.49). Those employed were less likely to walk the recommended ≥ 150 minutes for any purpose compared to those unemployed (OR=0.31, 95% CI=0.11-0.85) as were those who reported some difficulty walking for a quarter of a mile (OR=0.19, 95% CI=0.05-0.77). Other socio-environmental factors such as having care-giver responsibilities for elders, someone to walk with, or a dog in the household as well as Walk Score™ were not significantly associated with walking the recommended ≥ 150 minutes for any purpose in a typical week. Neighborhood perception appears to be an important factor associated with the walking behaviors of middle-aged and older overweight and obese individuals. Enhancing the neighborhood environment (e.g., providing walking trails) may promote walking among these individuals.Keywords: determinants of walking, obesity, older adults, physical activity
Procedia PDF Downloads 2591316 The Effect of Nanocomposite on the Release of Imipenem on Bacteria Causing Infections with Implants
Authors: Mohammad Hossein Pazandeh, Monir Doudi, Sona Rostampour Yasouri
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—Results The prudent administration of antibiotics aims to avoid the side effects and the microbes' resistance to antibiotics. An approach developing methods of local administration of antibiotics is especially required for localized infections caused by bacterial colonization of medical devices or implant materials. Among the wide variety of materials used as drug delivery systems, bioactive glasses (BG) have large utilization in regenerative medicine . firstly, the production of bioactive glass/nickel oxide/tin dioxide nanocomposite using sol-gel method, and then, the controlled release of imipenem from the double metal oxide/bioactive glass nanocomposite, and finally, the investigation of the antibacterial property of the nanocomposite. against a number of implant-related infectious agents. In this study, BG/SnO2 and BG/NiO single systema with different metal oxide present and BG/NiO/SnO2 nanocomposites were synthesized by sol-gel as drug carriers for tetracycline and imepinem. These two antibiotics were widely used for osteomyelitis because of its favorable penetration and bactericidal effect on all the probable osteomyelitis pathogens. The antibacterial activity of synthesized samples were evaluated against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa as bacteria model using disk diffusion method. The BG modification using metal oxides results to antibacterial property of samples containing metal oxide with highest efficiency for nancomposite. bioactivity of all samples was assessed by determining the surface morphology, structural and composition changes using scanning electron microscopy (SEM), FTIR and X-ray diffraction (XRD) spectroscopy, respectively, after soaking in simulated body fluid (SBF) for 28 days. The hydroxyapatite formation was clearly observed as a bioactivity measurement. Then, BG nanocomposite sample was loaded using two antibiotics, separately and their release profiles were studied. The BG nancomposite sample was shown the slow and continuous drug releasing for a period of 72 hours which is desirable for a drug delivery system. The loaded antibiotic nanocomposite sample retaining antibacterial property and showing inactivation effect against bacteria under test. The modified bioactive glass forming hydroxyapatite with controlled release drug and effective against bacterial infections can be introduced as scaffolds for bone implants after clinical trials for biomedical applications . Considering the formation of biofilm by infectious bacteria after sticking on the surfaces of implants, medical devices, etc. Also, considering the complications of traditional methods, solving the problems caused by the above-mentioned microorganisms in technical and biomedical industries was one of the necessities of this research.Keywords: antibacterial, bioglass, drug delivery system, sol- gel
Procedia PDF Downloads 611315 Powder Assisted Sheet Forming to Fabricate Ti Capsule Magnetic Hyperthermia Implant
Authors: Keigo Nishitani, Kohei Mizuta Mizuta, Kazuyoshi Kurita, Yukinori Taniguchi
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To establish mass production process of Ti capsule which has Fe powder inside as magnetic hyperthermia implant, we assumed that Ti thin sheet can be drawn into a φ1.0 mm die hole through the medium of Fe Powder and becomes outer shell of capsule. This study discusses mechanism of powder assisted deep drawing process by both of numerical simulation and experiment. Ti thin sheet blank was placed on die, and was covered by Fe powder layer without pressurizing. Then upper punch was indented on the Fe powder layer, and the blank can be drawn into die cavity as pressurized powder particles were extruded into die cavity from behind of the drawn blank. Distinct Element Method (DEM) has been used to demonstrate the process. To identify bonding parameters on Fe particles which are cohesion, tensile bond stress and inter particle friction angle, axial and diametrical compression failure test of Fe powder compact was conducted. Several density ratios of powder compacts in range of 0.70 - 0.85 were investigated and relationship between mean stress and equivalent stress was calculated with consideration of critical state line which rules failure criterion in consolidation of Fe powder. Since variation of bonding parameters with density ratio has been experimentally identified, and good agreement has been recognized between several failure tests and its simulation, demonstration of powder assisted sheet forming by using DEM becomes applicable. Results of simulation indicated that indent/drawing length of Ti thin sheet is promoted by smaller Fe particle size, larger indent punch diameter, lower friction coefficient between die surface and Ti sheet and certain degrees of die inlet taper angle. In the deep drawing test, we have made die-set with φ2.4 mm punch and φ1.0 mm die bore diameter. Pure Ti sheet with 100 μm thickness, annealed at 650 deg. C has been tested. After indentation, indented/drawn capsule has been observed by microscope, and its length was measured to discuss the feasibility of this capsulation process. Longer drawing length exists on progressive loading pass comparing with the case of single stroke loading. It is expected that progressive loading has an advantage of which extrusion of powder particle into die cavity with Ti sheet is promoted since powder particle layer can be rebuilt while the punch is withdrawn from the layer in each loading steps. This capsulation phenomenon is qualitatively demonstrated by DEM simulation. Finally, we have fabricated Ti capsule which has Fe powder inside for magnetic hyperthermia cancer care treatment. It is concluded that suggested method is possible to use the manufacturing of Ti capsule implant for magnetic hyperthermia cancer care.Keywords: metal powder compaction, metal forming, distinct element method, cancer care, magnetic hyperthermia
Procedia PDF Downloads 2981314 Introducing Data-Driven Learning into Chinese Higher Education English for Academic Purposes Writing Instructional Settings
Authors: Jingwen Ou
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Writing for academic purposes in a second or foreign language is one of the most important and the most demanding skills to be mastered by non-native speakers. Traditionally, the EAP writing instruction at the tertiary level encompasses the teaching of academic genre knowledge, more specifically, the disciplinary writing conventions, the rhetorical functions, and specific linguistic features. However, one of the main sources of challenges in English academic writing for L2 students at the tertiary level can still be found in proficiency in academic discourse, especially vocabulary, academic register, and organization. Data-Driven Learning (DDL) is defined as “a pedagogical approach featuring direct learner engagement with corpus data”. In the past two decades, the rising popularity of the application of the data-driven learning (DDL) approach in the field of EAP writing teaching has been noticed. Such a combination has not only transformed traditional pedagogy aided by published DDL guidebooks in classroom use but also triggered global research on corpus use in EAP classrooms. This study endeavors to delineate a systematic review of research in the intersection of DDL and EAP writing instruction by conducting a systematic literature review on both indirect and direct DDL practice in EAP writing instructional settings in China. Furthermore, the review provides a synthesis of significant discoveries emanating from prior research investigations concerning Chinese university students’ perception of Data-Driven Learning (DDL) and the subsequent impact on their academic writing performance following corpus-based training. Research papers were selected from Scopus-indexed journals and core journals from two main Chinese academic databases (CNKI and Wanfang) published in both English and Chinese over the last ten years based on keyword searches. Results indicated an insufficiency of empirical DDL research despite a noticeable upward trend in corpus research on discourse analysis and indirect corpus applications for material design by language teachers. Research on the direct use of corpora and corpus tools in DDL, particularly in combination with genre-based EAP teaching, remains a relatively small fraction of the whole body of research in Chinese higher education settings. Such scarcity is highly related to the prevailing absence of systematic training in English academic writing registers within most Chinese universities' EAP syllabi due to the Chinese English Medium Instruction policy, where only English major students are mandated to submit English dissertations. Findings also revealed that Chinese learners still held mixed attitudes towards corpus tools influenced by learner differences, limited access to language corpora, and insufficient pre-training on corpus theoretical concepts, despite their improvements in final academic writing performance.Keywords: corpus linguistics, data-driven learning, EAP, tertiary education in China
Procedia PDF Downloads 601313 Investigating Educator Perceptions of Body-Rich Language on Student Self-Image, Body-Consciousness and School Climate
Authors: Evelyn Bilias-Lolis, Emily Louise Winter
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Schools have a responsibility to implement school-wide frameworks that actively prevent, detect, and support all aspects of child development and learning. Such efforts can range from individual or classroom-level supports to school-wide primary prevention practices for the school’s infrastructure or climate. This study assessed the perceptions of educators across a variety of disciplines in Connecticut (i.e., elementary and secondary education, special education, school psychology, and school social work) on the perceived impact of their beliefs, language, and behavior about food and body consciousness on student self-image and school climate. Participants (N=50) completed a short electronic questionnaire measuring perceptions of how their behavior can influence their students’ opinions about themselves, their emerging self-image, and the overall climate of the school community. Secondly, the beliefs that were directly assessed in the first portion of the survey were further measured through the use of applied social vignettes involving students directly or as bystanders. Preliminary findings are intriguing. When asked directly, 100% of the respondents reported that what they say to students directly could influence student opinions about themselves and 98% of participants further agreed that their behavior both to and in front of students could impact a student’s developing self-image. Likewise, 82% of the sample agreed that their personal language and behavior affect the overall climate of a school building. However, when the above beliefs were assessed via applied social vignettes depicting routine social exchanges, results were significantly more widespread (i.e., results were evenly dispersed among levels of agreement and disagreement across participants in all areas). These preliminary findings offer humble but critical implications for informing integrated school wellness frameworks that aim to create body-sensitive school communities. Research indicates that perceptions about body image, attitudes about eating, and the onset of disordered eating practices surface in school-aged years. Schools provide a natural setting for instilling foundations for child wellness as a natural extension of existing school climate reform efforts. These measures do not always need to be expansive or extreme. Rather, educators have a ripe opportunity to become champions for health and wellness through increased self-awareness and subtle shifts in language and behavior. Future psychological research needs to continue to explore this line of inquiry using larger and more varied samples of educators in order to identify needs in teacher training and development that can yield positive and preventative health outcomes for children.Keywords: body-sensitive schools, integrated school health, school climate reform, teacher awareness
Procedia PDF Downloads 1581312 Hypersensitivity Reactions Following Intravenous Administration of Contrast Medium
Authors: Joanna Cydejko, Paulina Mika
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Hypersensitivity reactions are side effects of medications that resemble an allergic reaction. Anaphylaxis is a generalized, severe allergic reaction of the body caused by exposure to a specific agent at a dose tolerated by a healthy body. The most common causes of anaphylaxis are food (about 70%), Hymenoptera venoms (22%), and medications (7%), despite detailed diagnostics in 1% of people, the cause of the anaphylactic reaction was not indicated. Contrast media are anaphylactic agents of unknown mechanism. Hypersensitivity reactions can occur with both immunological and non-immunological mechanisms. Symptoms of anaphylaxis occur within a few seconds to several minutes after exposure to the allergen. Contrast agents are chemical compounds that make it possible to visualize or improve the visibility of anatomical structures. In the diagnosis of computed tomography, the preparations currently used are derivatives of the triiodide benzene ring. Pharmacokinetic and pharmacodynamic properties, i.e., their osmolality, viscosity, low chemotoxicity and high hydrophilicity, have an impact on better tolerance of the substance by the patient's body. In MRI diagnostics, macrocyclic gadolinium contrast agents are administered during examinations. The aim of this study is to present the results of the number and severity of anaphylactic reactions that occurred in patients in all age groups undergoing diagnostic imaging with intravenous administration of contrast agents. In non-ionic iodine CT and in macrocyclic gadolinium MRI. A retrospective assessment of the number of adverse reactions after contrast administration was carried out on the basis of data from the Department of Radiology of the University Clinical Center in Gdańsk, and it was assessed whether their different physicochemical properties had an impact on the incidence of acute complications. Adverse reactions are divided according to the severity of the patient's condition and the diagnostic method used in a given patient. Complications following the administration of a contrast medium in the form of acute anaphylaxis accounted for less than 0.5% of all diagnostic procedures performed with the use of a contrast agent. In the analysis period from January to December 2022, 34,053 CT scans and 15,279 MRI examinations with the use of contrast medium were performed. The total number of acute complications was 21, of which 17 were complications of iodine-based contrast agents and 5 of gadolinium preparations. The introduction of state-of-the-art contrast formulations was an important step toward improving the safety and tolerability of contrast agents used in imaging. Currently, contrast agents administered to patients are considered to be one of the best-tolerated preparations used in medicine. However, like any drug, they can be responsible for the occurrence of adverse reactions resulting from their toxic effects. The increase in the number of imaging tests performed with the use of contrast agents has a direct impact on the number of adverse events associated with their administration. However, despite the low risk of anaphylaxis, this risk should not be marginalized. The growing threat associated with the mass performance of radiological procedures with the use of contrast agents forces the knowledge of the rules of conduct in the event of symptoms of hypersensitivity to these preparations.Keywords: anaphylactic, contrast medium, diagnostic, medical imagine
Procedia PDF Downloads 621311 Applying a SWOT Analysis to Inform the Educational Provision of Learners with Autism Spectrum Disorders
Authors: Claire Sciberras
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Introduction: Autism Spectrum Disorder (ASD) has become recognized as being the most common childhood neurological condition. Indeed, numerous studies demonstrate an increase in the prevalence rate of children diagnosed with ASD. Concurrent with these findings, the European Agency for Special Needs and Inclusive Education reported a similar escalating tendency in prevalence also in Malta. Such an increase within the educational context in Malta has led the European Agency to call for increased support within educational settings in Malta. However, although research has addressed the positive impact of mainstream education on learners with ASD, empirical studies vis-à-vis the internal and external strengths and weaknesses present within the support provided in mainstream settings in Malta is distinctly limited. In light of the aforementioned argument, Malta would benefit from research which focuses on analysing the strengths, weaknesses, opportunities, and threats (SWOTs) which are present within the support provision of learners with ASD in mainstream primary schools. Such SWOT analysis is crucial as lack of appropriate opportunities might jeopardize the educational and social experiences of persons with ASD throughout their schooling. Methodology: A mixed methodological approach would be well suited to examine the provision of support of learners with ASD as the combination of qualitative and quantitative approaches allows researchers to collect a comprehensive range of data and validate their results. Hence, it is intended that questionnaires will be distributed to all the stakeholders involved so as to acquire a broader perspective to be collected from a wider group who provide support to students with ASD across schools in Malta. Moreover, the use of a qualitative approach in the form of interviews with a sample group will be implemented. Such an approach will be considered as it would potentially allow the researcher to gather an in-depth perspective vis-à-vis to the nature of the services which are currently provided to learners with ASD. The intentions of the study: Through the analysis of the data collected vis-à-vis to the SWOTs within the provision of support of learners with ASD it is intended that; i) a description in regards to the educational provision for learners with ASD within mainstream primary schools in Malta in light of the experiences and perceptions of the stakeholders involved will be acquired; ii) an analysis of the SWOTs which exist within the services for learners with ASD in primary state schools in Malta is carried out and iii) based on the SWOT analysis, recommendations that can lead to improvements in practice in the field of ASD in Malta and beyond will be provided. Conclusion: Due to the heterogeneity of individuals with ASD which spans across several deficits related to the social communication and interaction domain and also across areas linked to restricted, repetitive behavioural patterns, educational settings need to alter their standards according to the needs of their students. Thus, the standards established by schools throughout prior phases do not remain applicable forever, and therefore these need to be reviewed periodically in accordance with the diversities and the necessities of their learners.Keywords: autism spectrum disorders, mainstream educational settings, provision of support, SWOT analysis
Procedia PDF Downloads 1931310 Implementation of a PDMS Microdevice for the Improved Purification of Circulating MicroRNAs
Authors: G. C. Santini, C. Potrich, L. Lunelli, L. Vanzetti, S. Marasso, M. Cocuzza, C. Pederzolli
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The relevance of circulating miRNAs as non-invasive biomarkers for several pathologies is nowadays undoubtedly clear, as they have been found to have both diagnostic and prognostic value able to add fundamental information to patients’ clinical picture. The availability of these data, however, relies on a time-consuming process spanning from the sample collection and processing to the data analysis. In light of this, strategies which are able to ease this procedure are in high demand and considerable effort have been made in developing Lab-on-a-chip (LOC) devices able to speed up and standardise the bench work. In this context, a very promising polydimethylsiloxane (PDMS)-based microdevice which integrates the processing of the biological sample, i.e. purification of extracellular miRNAs, and reverse transcription was previously developed in our lab. In this study, we aimed at the improvement of the miRNA extraction performances of this micro device by increasing the ability of its surface to absorb extracellular miRNAs from biological samples. For this purpose, we focused on the modulation of two properties of the material: roughness and charge. PDMS surface roughness was modulated by casting with several templates (terminated with silicon oxide coated by a thin anti-adhesion aluminum layer), followed by a panel of curing conditions. Atomic force microscopy (AFM) was employed to estimate changes at the nanometric scale. To introduce modifications in surface charge we functionalized PDMS with different mixes of positively charged 3-aminopropyltrimethoxysilanes (APTMS) and neutral poly(ethylene glycol) silane (PEG). The surface chemical composition was characterized by X-ray photoelectron spectroscopy (XPS) and the number of exposed primary amines was quantified with the reagent sulfosuccinimidyl-4-o-(4,4-dimethoxytrityl) butyrate (s-SDTB). As our final end point, the adsorption rate of all these different conditions was assessed by fluorescence microscopy by incubating a synthetic fluorescently-labeled miRNA. Our preliminary analysis identified casting on thermally grown silicon oxide, followed by a curing step at 85°C for 1 hour, as the most efficient technique to obtain a PDMS surface roughness in the nanometric scaleable to trap miRNA. In addition, functionalisation with 0.1% APTMS and 0.9% PEG was found to be a necessary step to significantly increase the amount of microRNA adsorbed on the surface, therefore, available for further steps as on-chip reverse transcription. These findings show a substantial improvement in the extraction efficiency of our PDMS microdevice, ultimately leading to an important step forward in the development of an innovative, easy-to-use and integrated system for the direct purification of less abundant circulating microRNAs.Keywords: circulating miRNAs, diagnostics, Lab-on-a-chip, polydimethylsiloxane (PDMS)
Procedia PDF Downloads 3181309 Research on Land Use Pattern and Employment-Housing Space of Coastal Industrial Town Based on the Investigation of Liaoning Province, China
Authors: Fei Chen, Wei Lu, Jun Cai
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During the Twelve Five period, China promulgated industrial policies promoting the relocation of energy-intensive industries to coastal areas in order to utilize marine shipping resources. Consequently, some major state-owned steel and gas enterprises have relocated and resulted in a large-scale coastal area development. However, some land may have been over-exploited with seamless coastline projects. To balance between employment and housing, new industrial coastal towns were constructed to support the industrial-led development. In this paper, we adopt a case-study approach to closely examine the development of several new industrial coastal towns of Liaoning Province situated in the Bohai Bay area, which is currently under rapid economic growth. Our investigations reflect the common phenomenon of long distance commuting and a massive amount of vacant residences. More specifically, large plant relocation caused hundreds of kilometers of daily commute and enterprises had to provide housing subsidies and education incentives to motivate employees to relocate to coastal areas. Nonetheless, many employees still refuse to relocate due to job stability, diverse needs of family members and access to convenient services. These employees averaged 4 hours of commute daily and some who lived further had to reside in temporary industrial housing units and subject to long-term family separation. As a result, only a small portion of employees purchase new coastal residences but mostly for investment and retirement purposes, leading to massive vacancy and ghost-town phenomenon. In contrast to the low demand, coastal areas tend to develop large amount of residences prior to industrial relocation, which may be directly related to local government finances. Some local governments have sold residential land to developers to general revenue to support the subsequent industrial development. Subject to the strong preference of ocean-view, residential housing developers tend to select coast-line land to construct new residential towns, which further reduces the access of marine resources for major industrial enterprises. This violates the original intent of developing industrial coastal towns and drastically limits the availability of marine resources. Lastly, we analyze the co-existence of over-exploiting residential areas and massive vacancies in reference to the demand and supply of land, as well as the demand of residential housing units with the choice criteria of enterprise employees.Keywords: coastal industry town, commuter traffic, employment-housing space, outer suburb industrial area
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