Search results for: feeding duration
860 Technological Ensuring of the Space Reflector Antennas Manufacturing Process from Carbon Fiber Reinforced Plastics
Authors: Pyi Phyo Maung
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In the study, the calculations of the permeability coefficient, values of the volume and porosity of a unit cell of a woven fabric before and after deformation based on the geometrical parameters are presented. Two types of carbon woven fabric structures were investigated: standard type, which integrated the filament, has a cross sectional shape of a cylinder and spread tow type, which has a rectangular cross sectional shape. The space antennas reflector, which distinctive feature is the presence of the surface of double curvature, is considered as the object of the research. Modeling of the kinetics of the process of impregnation of the reflector for the two types of carbon fabric’s unit cell structures was performed using software RAM-RTM. This work also investigated the influence of the grid angle between warp and welt of the unit cell on the duration of impregnation process. The results showed that decreasing the angle between warp and welt of the unit cell, the decreasing of the permeability values were occurred. Based on the results of calculation samples of the reflectors, their quality was determined. The comparisons of the theoretical and experimental results have been carried out. Comparison of the two textile structures (standard and spread tow) showed that the standard textiles with circular cross section were impregnated faster than spread tows, which have a rectangular cross section.Keywords: vacuum assistant resin infusion, impregnation time, shear angle, reflector and modeling
Procedia PDF Downloads 273859 Post Covid-19 Landscape of Global Pharmaceutical Industry
Authors: Abu Zafor Sadek
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Pharmaceuticals were one of the least impacted business sectors during the corona pandemic as they are the center point of Covid-19 fight. Emergency use authorization, unproven indication of some commonly used drugs, self-medication, research and production capacity of an individual country, capacity of producing vaccine by many countries, Active Pharmaceutical Ingredients (APIs) related uncertainty, information gap among manufacturer, practitioners and user, export restriction, duration of lock-down, lack of harmony in transportation, disruption in the regulatory approval process, sudden increased demand of hospital items and protective equipment, panic buying, difficulties in in-person product promotion, e-prescription, geo-politics and associated issues added a new dimension to this industry. Although the industry maintains a reasonable growth throughout Covid-19 days; however, it has been characterized by both long- and short-term effects. Short-term effects have already been visible to so many countries, especially those who are import-dependent and have limited research capacity. On the other hand, it will take a few more time to see the long-term effects. Nevertheless, supply chain disruption, changes in strategic planning, new communication model, squeezing of job opportunity, rapid digitalization are the major short-term effects, whereas long-term effects include a shift towards self-sufficiency, growth pattern changes of certain products, special attention towards clinical studies, automation in operations, the increased arena of ethical issues etc. Therefore, this qualitative and exploratory study identifies the post-covid-19 landscape of the global pharmaceutical industry.Keywords: covid-19, pharmaceutical, businees, landscape
Procedia PDF Downloads 92858 Induction of Labor Using Misoprostol with or without Mifepristone in Intrauterine Death: A Randomized Controlled Study
Authors: Ajay Agrawal, Pritha Basnet, Achala Thakur, Pappu Rizal, Rubina Rai
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Context: Rapid expulsion of fetus in intrauterine fetal death (IUFD) is usually requested without any medical grounds for it. So; an efficient, safe method for induction of labor (IOL) is required. Objective: To determine if pre-treatment with mifepristone followed by IOL with misoprostol in late IUFD is more efficacious. Methods: We conducted a randomized controlled trial in 100 patients. Group-A women received single oral dose of 200 mg mifepristone, followed by induction with vaginal misoprostol after 24-hour. Group-B women were induced only with vaginal misoprostol. In each group 5 dose of misoprostol was used 4 hourly. If first cycle was unsuccessful, after break of 12 hour, second course of misoprostol was started. The primary outcome was a measure of induction to delivery time and vaginal delivery within 24 hours. Secondary outcome was to measure need of oxytocin and complications. Results: Maternal age, parity and period of gestation were comparable between groups. Number of misoprostol dose needed in group A was significantly less than group B. Mann Whitney U test showed, women in group A had significantly earlier onset of labor, however total induction to delivery interval was not significant. In group-A, 85.7% delivered within 24 hours of first dose of misoprostol while in group-B 70% delivered within 24 hour (p=0.07). More women in Group B required oxytocin. Conclusion: Pretreatment with mifepristone before IOL following late IUFD is an effective and safe regimen. It appears to shorten the duration of induction to onset of labor.Keywords: induction of labor, intrauterine fetal death, mifepristone, misoprostol
Procedia PDF Downloads 377857 Substantial Fatigue Similarity of a New Small-Scale Test Rig to Actual Wheel-Rail System
Authors: Meysam Naeimi, Zili Li, Roumen Petrov, Rolf Dollevoet, Jilt Sietsma, Jun Wu
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The substantial similarity of fatigue mechanism in a new test rig for rolling contact fatigue (RCF) has been investigated. A new reduced-scale test rig is designed to perform controlled RCF tests in wheel-rail materials. The fatigue mechanism of the rig is evaluated in this study using a combined finite element-fatigue prediction approach. The influences of loading conditions on fatigue crack initiation have been studied. Furthermore, the effects of some artificial defects (squat-shape) on fatigue lives are examined. To simulate the vehicle-track interaction by means of the test rig, a three-dimensional finite element (FE) model is built up. The nonlinear material behaviour of the rail steel is modelled in the contact interface. The results of FE simulations are combined with the critical plane concept to determine the material points with the greatest possibility of fatigue failure. Based on the stress-strain responses, by employing of previously postulated criteria for fatigue crack initiation (plastic shakedown and ratchetting), fatigue life analysis is carried out. The results are reported for various loading conditions and different defect sizes. Afterward, the cyclic mechanism of the test rig is evaluated from the operational viewpoint. The results of fatigue life predictions are compared with the expected number of cycles of the test rig by its cyclic nature. Finally, the estimative duration of the experiments until fatigue crack initiation is roughly determined.Keywords: fatigue, test rig, crack initiation, life, rail, squats
Procedia PDF Downloads 515856 Cutaneous Sarcoidosis Treated with Narrow Band Ultraviolet B (NBUVB) Phototherapy
Authors: Hannah Riva, Sarah Mazal, Jessica L. Marquez, Michael Rains
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A 70-year-old female with a Fitzpatrick skin phenotype II presented with a 13-year history of a scaly rash located on the left breast and bilateral pretibial regions. The patient’s past medical history was otherwise unremarkable, with the exception of surgery involving the left breast. Physical examination revealed infiltrative hyperpigmented scaly plaques and nodules located on the left breast and pretibial regions bilaterally. A negative systemic workup excluded organ involvement. A clinical diagnosis of cutaneous sarcoidosis was made. Prior treatments included triamcinolone 0.1% topical cream and clobetasol 0.05% ointment, which failed to show improvement. Full-body narrow-band UVB (NBUVB) treatment was performed on a tri-weekly basis for eight months. NBUVB dosage was slowly titrated from 300 mJ/cm2 to a final dose of 1800 mJ/cm2 to prevent discomfort and burning sensations. Throughout the duration of her treatment, the patient adhered to a regimen of clobetasol 0.05% topical ointment applied twice daily in two-week intervals. Improvement was noticed after two months, with continued improvement up to eight months. The patient is continuing NBUVB phototherapy treatments for maintenance. In our case, NBUVB phototherapy treatment demonstrated promising results with improvement after two months of treatment. Physicians should consider NBUVB phototherapy as an effective option for patients presenting with cutaneous sarcoidosis.Keywords: dermatology, sarcoidosis, phototherapy, ultraviolet
Procedia PDF Downloads 72855 The Effects of Orally Administered Bacillus Coagulans and Inulin on Prevention and Progression of Rheumatoid Arthritis in Rats
Authors: Khadijeh Abhari, Seyed Shahram Shekarforoush, Saeid Hosseinzadeh
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Probiotics have been considered as an approach to treat and prevent a wide range of inflammatory diseases. The spore forming probiotic strain Bacillus coagulans has demonstrated anti-inflammatory and immune-modulating effects in both animals and humans. The prebiotic, inulin, also potentially affects the immune system as a result of the change in the composition or fermentation profile of the gastrointestinal microbiota. An in vivo trial was conducted to evaluate the effects of probiotic B. coagulans, and inulin, either separately or in combination, on down regulate immune responses and progression of rheumatoid arthritis using induced arthritis rat model. Forty-eight male Wistar rats were randomly divided into 6 groups and fed as follow: 1) control: Normal healthy rats fed by standard diet, 2) Disease control (RA): Arthritic induced (RA) rats fed by standard diet, 3) Prebiotic (PRE): RA+ 5% w/w long chain inulin, 4) Probiotic (PRO): RA+ 109 spores/day B. coagulans by orogastric gavage, 5) Synbiotic (SYN): RA+ 5% w/w long chain inulin and 109 spores/day B. coagulans and 6) Treatment control: (INDO): RA+ 3 mg/kg/day indomethacin by orogastric gavage. Feeding with mentioned diets started on day 0 and continued to the end of study. On day 14, rats were injected with complete Freund’s adjuvant (CFA) to induce arthritis. Arthritis activity was evaluated by biochemical parameters and paw thickness. Biochemical assay for Fibrinogen (Fn), Serum Amyloid A (SAA), TNF-α and Alpha-1-acid glycoprotein (α1AGp) was performed on day 21, 28 and 35 (1, 2 and 3 weeks post RA induction). Pretreatment with PRE, PRO and SYN diets significantly inhibit SAA and Fn production in arthritic rats (P < 0.001). A significant decrease in production of pro-inflammatory cytokines, TNF-α, was seen in PRE, PRO and SYN groups (P < 0.001) which was similar to the effect of the anti-inflammatory drug Indomethacin. Further, there were no significant anti-inflammatory effects observed following different treatments using α1AGp as a RA indicator. Pretreatment with all supplied diets significantly inhibited the development of paw swelling induced by CFA (P < 0.001). Conclusion: Results of this study support that oral intake of probiotic B. coagulans and inulin are able to improve biochemical and clinical parameters of induced RA in rat.Keywords: rheumatoid arthritis, bacillus coagulans, inulin, animal model
Procedia PDF Downloads 356854 Determinants of Non-Performing Loans: An Empirical Investigation of Bank-Specific Micro-Economic Factors
Authors: Amir Ikram, Faisal Ijaz, Qin Su
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The empirical study was undertaken to explore the determinants of non-performing loans (NPLs) of small and medium enterprises (SMEs) sector held by the commercial banks. Primary data was collected through well-structured survey questionnaire from credit analysts/bankers of 42 branches of 9 commercial banks, operating in the district of Lahore (Pakistan), for 2014-2015. Selective descriptive analysis and Pearson chi-square technique were used to illustrate and evaluate the significance of different variables affecting NPLs. Branch age, duration of the loan, and credit policy were found to be significant determinants of NPLs. The study proposes that bank-specific and SME-specific microeconomic variables directly influence NPLs, while macroeconomic factors act as intermediary variables. Framework exhibiting causal nexus of NPLs was also drawn on the basis of empirical findings. The results elaborate various origins of NPLs and suggest that they are primarily instigated by the loan sanctioning procedure of the financial institution. The paper also underlines the risk management practices adopted by the bank at branch level to averse the risk of loan default. Empirical investigation of bank-specific microeconomic factors of NPLs with respect to Pakistan’s economy is the novelty of the study. Broader strategic policy implications are provided for credit analysts and entrepreneurs.Keywords: commercial banks, microeconomic factors, non-performing loans, small and medium enterprises
Procedia PDF Downloads 259853 S. S. L. Andrade, E. A. Souza, L. C. L. Santos, C. Moraes, A. K. C. L. Lobato
Authors: Fazal Said, Mian Inayatullah
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Various insect visitors in common and honeybees in particular are considered to be accountable for 80-85% of pollination services for numerous crops worldwide. Pollinators not only increase crop yield but also improve quality of produce as well. The present investigation is therefore, an endeavor to assess the visitation pattern of honeybees, Apis florea (Hymenopterae: Apidae) in sunflower (Helianthus annuus L.). The current research trial was carried out at New Developmental Farm (NDF), The University of Agriculture Peshawar, (34.01° N, 71.53° E) Khyber Pakhtunkhwa-Pakistan during 2012 and 2013. Different observations on the foraging behavior of A. florea’s individuals were made from 0800 hr in the morning and continued until 1800 hr in the evening. Hence, total duration of foraging activity of A. florea individuals was comprised of 10 hours. It was found that two peaks of visitation/foraging occurred between 1400 to 1600 hr of the day. First peak of foraging was recorded at 1600hr, where 15 individuals of honeybees/3 m2 were counted to be engaged in foraging sunflower blooms. Second peak visitation was recorded with a total of 12 bees/3 m2 at 1400 hrs of the day. Visitations of A. florea were observed to its minimum intensity of only 07 individuals during late hours of the day as evening approached after 1800 hrs. Similarly, due to more number of pollens and nectars on flowers, high frequency of A. florea were found engaged in foraging during 20th and 25th day after initiation of blooms on sunflower. Minimum numbers of honeybees were recorded during initial and very last days of flowering due to less number of plants with blooms and less availability of pollen and nectar on flowers.Keywords: apis florea, days after flowering, daily hours, sunflower, visitation pattern
Procedia PDF Downloads 635852 Eliciting and Confirming Data, Information, Knowledge and Wisdom in a Specialist Health Care Setting - The Wicked Method
Authors: Sinead Impey, Damon Berry, Selma Furtado, Miriam Galvin, Loretto Grogan, Orla Hardiman, Lucy Hederman, Mark Heverin, Vincent Wade, Linda Douris, Declan O'Sullivan, Gaye Stephens
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Healthcare is a knowledge-rich environment. This knowledge, while valuable, is not always accessible outside the borders of individual clinics. This research aims to address part of this problem (at a study site) by constructing a maximal data set (knowledge artefact) for motor neurone disease (MND). This data set is proposed as an initial knowledge base for a concurrent project to develop an MND patient data platform. It represents the domain knowledge at the study site for the duration of the research (12 months). A knowledge elicitation method was also developed from the lessons learned during this process - the WICKED method. WICKED is an anagram of the words: eliciting and confirming data, information, knowledge, wisdom. But it is also a reference to the concept of wicked problems, which are complex and challenging, as is eliciting expert knowledge. The method was evaluated at a second site, and benefits and limitations were noted. Benefits include that the method provided a systematic way to manage data, information, knowledge and wisdom (DIKW) from various sources, including healthcare specialists and existing data sets. Limitations surrounded the time required and how the data set produced only represents DIKW known during the research period. Future work is underway to address these limitations.Keywords: healthcare, knowledge acquisition, maximal data sets, action design science
Procedia PDF Downloads 359851 Effects of Drying Method and Seed Priming Duration on Coffee Seed and Seedling Quality
Authors: Taju Mohammednur, Tesfaye Megersa, Karta Kaske
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Coffee is an economically important cash crop in Ethiopia. However, the conditions under which coffee seeds are dried and processed significantly affect the seedling quality and productivity. The objective of this study was to evaluate the effect of pre-sowing treatments and drying methods on the physiological quality of coffee seeds and seedlings. The study included two coffee varieties (74110, 75227), two drying conditions (under-shade drying room, open sun), and five durations of seed hydro priming (6, 8, 18, 24 hours, and an untreated control). Factorial combinations of the three factors were laid out in a Completely Randomized Design of three replications. Results indicated that the highest germination percentage (91%), emergence rate (90%), and seedling vigor index-I (2236 cm %) were recorded for seeds dried under-shade drying room. In contrast, the lowest values of germination percentage, emergence rate, and vigor index were observed for seeds dried under open sun. There was a significant difference in seed germination based on hydro priming time, with the highest germination percentage (83%) recorded for seeds soaked for 6 hours, followed by 24 hours (83%). The lowest germination percentage (77%) was recorded for un-soaked seeds. In conclusion, drying seeds under shade is better for coffee seed quality, and hydro priming has improved seedling vigor. However, further investigation into seed priming methods and preservation techniques for primed seeds is necessary to improve coffee seed quality.Keywords: coffee, germination, seed drying, seed longevity, seed priming
Procedia PDF Downloads 28850 Thermo-Mechanical Behavior of Steel-Wood Connections of Wooden Structures Under the Effect of a Fire
Authors: Ahmed Alagha, Belkacem Lamri, Abdelhak Kada.
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Steel-wood assemblies often have complex geometric configurations whose overall behavior under the effect of a fire is conditioned by the thermal response, by combining the two materials steel and wood, whose thermal characteristics are greatly influenced by high temperatures. The objective of this work is to study the thermal behavior of a steel-wood connection, with or without insulating material, subjected to an ISO834 standard fire model. The analysis is developed by the analytical approach using the Eurocode, and numerically, by the finite element method, through the ANSYS calculation code. The design of the connections is evaluated at room temperature taking the cases of single shear and double shear. The thermal behavior of the connections is simulated in transient state while taking into account the modes of heat transfer by convection and by radiation. The variation of temperature as a function of time is evaluated in different positions of the connections while talking about the heat produced and the formation of the carbon layer. The results relate to the temperature distributions in the connection elements as a function of the duration of the fire. The results of the thermal analysis show that the temperature increases rapidly and reaches more than 260 °C in the steel material for an hour of exposure to fire. The temperature development in wood material is different from that in steel because of its thermal properties. Wood heats up on the outside and burns, its surface can reach very high temperatures in points on the surface.Keywords: Eurocode 5, finite elements, ISO834, simple shear, thermal behaviour, wood-steel connection
Procedia PDF Downloads 85849 Effect of Preoperative Single Dose Dexamethasone and Lignocaine on Post-Operative Quality of Recovery and Pain Relief after Laparoscopic Cholecystectomy
Authors: Gurjeet Khurana, Surender Singh, Poonam Arora, Praveendra K. Sachan
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Introduction: Post-operative quality of recovery is the key outcome in the perspective of anesthesiologist. It is directly related to patient satisfaction. This is unsurprising, considering most aspects of a poor quality recovery after surgery will impair satisfaction with care. This study was thus undertaken to evaluate effects of Dexamethasone and Lignocaine on Quality of Recovery using QoR- 40 questionnaire and compare their effects. Material and methods: After obtaining the ethical committee approval and written informed consent, 67 patients of 18-60 years, ASA grade I and II scheduled for elective laparoscopic cholecystectomy were randomly allocated into two groups. Group I of 34 patients received 2mg/kg lignocaine diluted to 10ml with normal saline. Group 2 of 33 patients received 0.1 mg/kg I/V Dexamethasone diluted to 10ml with normal saline. QoR-40 was assessed on pre-operative day, and again QoR-40 was assessed at 24 hr post-operative day-1. Postoperative pain scores, nausea and vomiting and shoulder pain were secondary outcomes. Results: The Global QoR-40 was more than 180 at 24 hr in both the groups. The Dexamethasone group had higher Global QoR-40 than lignocaine group 187.94 v/s 182.85. Amongst dimensions of QoR-40 Dexamethasone had statistically better physical comfort, physical independence, and pain relief as compared to Lignocaine. Positive items had excellent responses in Dexamethasone group. Headache, backache and sore throat were also less severe in Dexamethasone group as compared to Lignocaine group. Dexamethasone group had lower VAS compared to lignocaine group. Similarly, there was less fentanyl consumption in dexamethasone group (364.08 ± 127.31) in postoperative period when compared to the lignocaine group (412.31 ± 147.8). Group receiving dexamethasone had 36% increase in appetite compared to lignocaine group (17.6%), which facilitated early oral feeding. Frequency of PONV was less in group-2 at different time interval as compared to group 1. Total episode of PONV were 18 in group 1 and 7 in group 2. Statistically significant difference was seen among two groups (p value= 0.007). Use of antiemetic was more in group 1 as compared to group 2 at all the times, though it was not statistically significant at different time intervals. Antiemetics were administered to 18 patients in group 1 as compared to 5 patients in group 2 postoperatively. Statistically significant difference (p value= 0.011) was seen in total antiemetic consumption. Conclusion: Our study demonstrated that pre-operative administration of a single dose of dexamethasone enhanced the quality of recovery after laparoscopic cholecystectomy as compared to Lignocaine bolus dose.Keywords: dexamethasone, lignocaine, QoR-40 questionnaire, quality of recovery
Procedia PDF Downloads 122848 Surface Acoustic Wave (SAW)-Induced Mixing Enhances Biomolecules Kinetics in a Novel Phase-Interrogation Surface Plasmon Resonance (SPR) Microfluidic Biosensor
Authors: M. Agostini, A. Sonato, G. Greco, M. Travagliati, G. Ruffato, E. Gazzola, D. Liuni, F. Romanato, M. Cecchini
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Since their first demonstration in the early 1980s, surface plasmon resonance (SPR) sensors have been widely recognized as useful tools for detecting chemical and biological species, and the interest of the scientific community toward this technology has known a rapid growth in the past two decades owing to their high sensitivity, label-free operation and possibility of real-time detection. Recent works have suggested that a turning point in SPR sensor research would be the combination of SPR strategies with other technologies in order to reduce human handling of samples, improve integration and plasmonic sensitivity. In this light, microfluidics has been attracting growing interest. By properly designing microfluidic biochips it is possible to miniaturize the analyte-sensitive areas with an overall reduction of the chip dimension, reduce the liquid reagents and sample volume, improve automation, and increase the number of experiments in a single biochip by multiplexing approaches. However, as the fluidic channel dimensions approach the micron scale, laminar flows become dominant owing to the low Reynolds numbers that typically characterize microfluidics. In these environments mixing times are usually dominated by diffusion, which can be prohibitively long and lead to long-lasting biochemistry experiments. An elegant method to overcome these issues is to actively perturb the liquid laminar flow by exploiting surface acoustic waves (SAWs). With this work, we demonstrate a new approach for SPR biosensing based on the combination of microfluidics, SAW-induced mixing and the real-time phase-interrogation grating-coupling SPR technology. On a single lithium niobate (LN) substrate the nanostructured SPR sensing areas, interdigital transducer (IDT) for SAW generation and polydimethylsiloxane (PDMS) microfluidic chambers were fabricated. SAWs, impinging on the microfluidic chamber, generate acoustic streaming inside the fluid, leading to chaotic advection and thus improved fluid mixing, whilst analytes binding detection is made via SPR method based on SPP excitation via gold metallic grating upon azimuthal orientation and phase interrogation. Our device has been fully characterized in order to separate for the very first time the unwanted SAW heating effect with respect to the fluid stirring inside the microchamber that affect the molecules binding dynamics. Avidin/biotin assay and thiol-polyethylene glycol (bPEG-SH) were exploited as model biological interaction and non-fouling layer respectively. Biosensing kinetics time reduction with SAW-enhanced mixing resulted in a ≈ 82% improvement for bPEG-SH adsorption onto gold and ≈ 24% for avidin/biotin binding—≈ 50% and 18% respectively compared to the heating only condition. These results demonstrate that our biochip can significantly reduce the duration of bioreactions that usually require long times (e.g., PEG-based sensing layer, low concentration analyte detection). The sensing architecture here proposed represents a new promising technology satisfying the major biosensing requirements: scalability and high throughput capabilities. The detection system size and biochip dimension could be further reduced and integrated; in addition, the possibility of reducing biological experiment duration via SAW-driven active mixing and developing multiplexing platforms for parallel real-time sensing could be easily combined. In general, the technology reported in this study can be straightforwardly adapted to a great number of biological system and sensing geometry.Keywords: biosensor, microfluidics, surface acoustic wave, surface plasmon resonance
Procedia PDF Downloads 280847 Generating 3D Battery Cathode Microstructures using Gaussian Mixture Models and Pix2Pix
Authors: Wesley Teskey, Vedran Glavas, Julian Wegener
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Generating battery cathode microstructures is an important area of research, given the proliferation of the use of automotive batteries. Currently, finite element analysis (FEA) is often used for simulations of battery cathode microstructures before physical batteries can be manufactured and tested to verify the simulation results. Unfortunately, a key drawback of using FEA is that this method of simulation is very slow in terms of computational runtime. Generative AI offers the key advantage of speed when compared to FEA, and because of this, generative AI is capable of evaluating very large numbers of candidate microstructures. Given AI generated candidate microstructures, a subset of the promising microstructures can be selected for further validation using FEA. Leveraging the speed advantage of AI allows for a better final microstructural selection because high speed allows for the evaluation of many more candidate microstructures. For the approach presented, battery cathode 3D candidate microstructures are generated using Gaussian Mixture Models (GMMs) and pix2pix. This approach first uses GMMs to generate a population of spheres (representing the “active material” of the cathode). Once spheres have been sampled from the GMM, they are placed within a microstructure. Subsequently, the pix2pix sweeps over the 3D microstructure (iteratively) slice by slice and adds details to the microstructure to determine what portions of the microstructure will become electrolyte and what part of the microstructure will become binder. In this manner, each subsequent slice of the microstructure is evaluated using pix2pix, where the inputs into pix2pix are the previously processed layers of the microstructure. By feeding into pix2pix previously fully processed layers of the microstructure, pix2pix can be used to ensure candidate microstructures represent a realistic physical reality. More specifically, in order for the microstructure to represent a realistic physical reality, the locations of electrolyte and binder in each layer of the microstructure must reasonably match the locations of electrolyte and binder in previous layers to ensure geometric continuity. Using the above outlined approach, a 10x to 100x speed increase was possible when generating candidate microstructures using AI when compared to using a FEA only approach for this task. A key metric for evaluating microstructures was the battery specific power value that the microstructures would be able to produce. The best generative AI result obtained was a 12% increase in specific power for a candidate microstructure when compared to what a FEA only approach was capable of producing. This 12% increase in specific power was verified by FEA simulation.Keywords: finite element analysis, gaussian mixture models, generative design, Pix2Pix, structural design
Procedia PDF Downloads 107846 Antimicrobial Evaluation of Polyphenon 60 and Ciprofloxacin Loaded Nano Emulsion against Uropathogenic Escherichia coli Bacteria and Its in vivo Analysis
Authors: Atinderpal Kaur, Shweta Dang
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Our aim is to develop a nanoemulsion-based delivery system containing polyphenon 60 (P60) and ciprofloxacin (Cipro) for intravaginal delivery to treat urinary tract infection. In the present study Polyphenon 60 (P60) and ciprofloxacin (Cipro) were loaded in a single nano emulsion (NE) system via ultra-sonication technique and characterized for particle size, in vitro release and antibacterial efficacy against Bcl-2 level Escherichia coli bacteria. To determine in vivo pharmacokinetic parameters and intravaginal transportation of NE, gamma scintigraphy and biodistribution study was conducted by radiolabelling NE with technetium pertechnetate (99mTc). The preliminary antibacterial investigation showed synergy between these compounds with FICindex of 0.42. The developed formulation showed zeta potential +55.3 and particle size of 151.7 nm, with PDI of 0.196. The in vitro release percentage of P60 at the end of 7th hours was 94.8 ± 0.9 % whereas the release for Cipro was 75.1± 0.15 % in simulated vaginal media. MBC was identified and the findings demonstrated that in both ESBL (Extended Spectrum β- lactamase) and MBL (Metallo β- lactamase) cultures the P60+Cipro NE showed inhibition of growth of all the isolates at 2 mg/ml dilutions. The percentage per gram of radiolabelled drug was found (3.50±0.26) and (3.81±0.30) in kidney and urinary bladder, respectively at 3 h. From the findings, it was concluded that the developed P60+Cipro NE was transported efficiently throughout the target organs, had long duration of action and high biocompatibility via intravaginal administration as compared to oral administration.Keywords: ciprofloxacin, gamma scintigraphy, intravaginal drug delivery, Polyphenon 60
Procedia PDF Downloads 319845 Comparison of Virtual and Face to Face Training Program in Reducing Pain and Quality of Life of Female Students with Dysmenorrhea
Authors: Nilofar Mohammadi Ahvazi, Somayeh Ansari, Mohammad Hossein Haghighizadeh, Zahra Abbaspoor
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Introduction: Dysmenorrhea is one of the common causes of decreased efficiency at work, education and decreased quality of life of women. The aim of this study was to compare virtual and face-to-face training programs in reducing pain and improving the quality of life of female students with primary dysmenorrhea in Ahvaz. Methods: In this quasi-experimental study, 112 female students living in the dormitories of Ahvaz University of Medical Sciences with moderate to severe primary dysmenorrhea were divided into two face-to-face and virtual groups using blocks of size 4. The educational intervention was carried out in two groups at a specific hour before the start of the first menstrual cycle. Data were collected with the help of a quality-of-life questionnaire (Sf-36), visual analog scale (VAS), and McGill questionnaire and were analyzed using descriptive and analytical tests with the help of SPSS version 25 software. Findings: The average age of the research subjects was 25.93±2.00, and the average duration of dysmenorrhea in each period was 2.49 days. There was no statistically significant difference in the quality of life of the students before the intervention, but after the educational intervention, a statistically significant difference was found between the two groups in terms of the quality of life and its dimensions (p<0.001). They were the same before the intervention, But after the intervention, the difference became significant (p<0.001). Conclusion: The virtual training method, like face-to-face training, can improve the quality of life and reduce the severity of primary dysmenorrhea pain in students. Therefore, depending on the conditions, both educational methods can be used.Keywords: primary dysmenorrhea, face-to-face training, virtual, training
Procedia PDF Downloads 42844 The Interaction between Blood-Brain Barrier and the Cerebral Lymphatics Proposes Therapeutic Method for Alzheimer’S Disease
Authors: M. Klimova, O. Semyachkina-Glushkovskaya, J. Kurts, E. Zinchenko, N. Navolokin, A. Shirokov, A. Dubrovsky, A. Abdurashitov, A. Terskov, A. Mamedova, I. Agranovich, T. Antonova, I. Blokhina
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The direction for research of Alzheimer's disease is to find an effective non-invasive and non-pharmacological way of treatment. Here we tested our hypothesis that the opening of the blood-brain barrier (BBB) induces activation of lymphatic drainage and clearing functions that can be used as a method for non-invasive stimulation of clearance of beta-amyloid and therapy of Alzheimer’s disease (AD). To test our hypothesis, in this study on healthy male mice we analyzed the interaction between BBB opening by repeated loud music (100-10000 Hz, 100 dB, duration 2 h: 60 sec – sound; 60 sec - pause) and functional changes in the meningeal lymphatic vessels (MLVs). We demonstrate clearance of dextran 70 kDa (i.v. injection), fluorescent beta-amyloid (intrahippocampal injection) and gold nanorods (intracortical injection) via MLV that significantly increased after the opening of BBB. Our studies also demonstrate that the BBB opening was associated with the improvement of neurocognitive status in mice with AD. Thus, we uncover therapeutic effects of BBB opening by loud music, such as non-invasive stimulation of lymphatic clearance of beta-amyloid in mice with AD, accompanied by improvement of their neurocognitive status. Our data are consistent with other results suggesting the therapeutic effect of BBB opening by focused ultrasound without drugs for patients with AD. This research was supported by a grant from RSF 18-75-10033Keywords: Alzheimer's disease, beta-amyloid, blood-brain barrier, meningeal lymphatic vessels, repeated loud music
Procedia PDF Downloads 142843 A Pilot Study of Robot Reminiscence in Dementia Care
Authors: Ryuji Yamazaki, Masahiro Kochi, Weiran Zhu, Hiroko Kase
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In care for older adults, behavioral and psychological symptoms of dementia (BPSD) like agitation and aggression are distressing for patients and their caretakers, often resulting in premature institutionalization with increased costs of care. To improve mood and mitigate symptoms, as a non-pharmaceutical approach, emotion-oriented therapy like reminiscence work is adopted in face-to-face communication. Telecommunication support is expected to be provided by robotic media as a bridge for digital divide for those with dementia and facilitate social interaction both verbally and nonverbally. The purpose of this case study is to explore the conditions in which robotic media can effectively attract attention from older adults with dementia and promote their well-being. As a pilot study, we introduced the pillow-phone Hugvie®, a huggable humanly shaped communication medium to five residents with dementia at a care facility, to investigate how the following conditions work for the elderly when they use the medium; 1) no sound, 2) radio, non-interactive, 3) daily conversation, and 4) reminiscence work. As a result, under condition 4, reminiscence work, the five participants kept concentration in interacting with the medium for a longer duration than other conditions. In condition 4, they also showed larger amount of utterances than under other conditions. These results indicate that providing topics related to personal histories through robotic media could affect communication positively and should, therefore, be further investigated. In addition, the issue of ethical implications by using persuasive technology that affects emotions and behaviors of older adults is also discussed.Keywords: BPSD, reminiscence, tactile telecommunication, utterances
Procedia PDF Downloads 173842 Tailoring of ECSS Standard for Space Qualification Test of CubeSat Nano-Satellite
Authors: B. Tiseo, V. Quaranta, G. Bruno, G. Sisinni
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There is an increasing demand of nano-satellite development among universities, small companies, and emerging countries. Low-cost and fast-delivery are the main advantages of such class of satellites achieved by the extensive use of commercial-off-the-shelf components. On the other side, the loss of reliability and the poor success rate are limiting the use of nano-satellite to educational and technology demonstration and not to the commercial purpose. Standardization of nano-satellite environmental testing by tailoring the existing test standard for medium/large satellites is then a crucial step for their market growth. Thus, it is fundamental to find the right trade-off between the improvement of reliability and the need to keep their low-cost/fast-delivery advantages. This is particularly even more essential for satellites of CubeSat family. Such miniaturized and standardized satellites have 10 cm cubic form and mass no more than 1.33 kilograms per 1 unit (1U). For this class of nano-satellites, the qualification process is mandatory to reduce the risk of failure during a space mission. This paper reports the description and results of the space qualification test campaign performed on Endurosat’s CubeSat nano-satellite and modules. Mechanical and environmental tests have been carried out step by step: from the testing of the single subsystem up to the assembled CubeSat nano-satellite. Functional tests have been performed during all the test campaign to verify the functionalities of the systems. The test duration and levels have been selected by tailoring the European Space Agency standard ECSS-E-ST-10-03C and GEVS: GSFC-STD-7000A.Keywords: CubeSat, nano-satellite, shock, testing, vibration
Procedia PDF Downloads 186841 Tick Infestation and its Implications on Health and Welfare of Cattle under Pastoral System in Nigeria
Authors: Alabi Olufemi, Adeyanju Taiwo, Oloruntoba Oluwasegun, Adeleye Bobola, Alabi Oyekemi
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The pastoral system is a predominant form of cattle production in Nigeria, characterized by extensive grazing on communal lands. However, this system is challenged by various factors, including tick infestation, which significantly affects cattle health and welfare hence this investigation which aims to provide an in-depth understanding of tick infestation in the context of Nigerian pastoral systems, emphasizing its impact on cattle health and welfare. The country harbors a diverse array of tick species that affect cattle. These ticks belong to different genera, including Rhipicephalus, Amblyomma, and Hyalomma, among others. Each species has unique characteristics, life cycles, and host preferences, contributing to the complexity of tick infestation dynamics in pastoral settings. Tick infestation has numerous detrimental effects on cattle health. The direct effects include blood loss, anemia, skin damage due to feeding, and the transmission of pathogens that cause diseases such as anaplasmosis, babesiosis, and theileriosis. Indirectly, tick infestation can lead to reduced productivity, weight loss, and increased susceptibility to other diseases.The welfare of cattle in Nigerian pastoral systems is significantly impacted by tick infestation. Infested cattle often exhibit signs of distress, including restlessness, reduced grazing activity, and altered behavior. Furthermore, the discomfort caused by tick bites can lead to chronic stress, compromising the overall welfare of the animals. Effective tick control is crucial for mitigating the impact of infestation on cattle health and welfare. Strategies such as acaricide application, pasture management, genetic selection for tick resistance cattle, and vaccination against tick-borne diseases are commonly used. Tick infestation presents a significant challenge to cattle production under the pastoral system in Nigeria. It not only impacts cattle health but also compromises their welfare. Addressing the issue of tick infestation requires a multifaceted approach that integrates effective control strategies with sustainable management practices. Further research is needed to develop tailored interventions that account for the unique characteristics of Nigerian pastoral systems, ultimately ensuring the well-being and productivity of cattle in these settings.Keywords: tick infestation, pastoral system, welfare, cattle
Procedia PDF Downloads 55840 Isotretinoin and Psychiatric Adverse Events: A Review of the Evidence
Authors: Thodoris Tsagkaris, Marios Stavropoulos, Panagiotis Theodosis-Nobelos, Charalampos Triantis
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Isotretinoin is a widely used therapeutic for the treatment of acne vulgaris and various other skin disorders. However, since its approval, many side effects and contraindications have been described, particularly important, such as teratogenicity as well as liver disease and dermal deterioration. In a very important allegation, isotretinoin has been linked with psychiatric symptoms like depression, suicidal ideation, schizophrenia, and hypervitaminosis A syndrome characteristics. These adverse effects have raised significant concerns regarding the safety of isotretinoin. Numerous studies and research have associated isotretinoin with side effects on the mental health of patients and have proposed plausible mechanisms regarding this suspected causative relationship. However, the evidence is still contradicting, and the data disperse, making their validity less valuable. Thus, in the present study, we aim to analyze further the available literature and present a complete analysis of the side effects of isotretinoin, with particular emphasis on the effects it may have on the mental health of patients. The review is based on international articles from broad scientific electronic databases like PubMed and Scopus. This review concludes that although many studies have associated isotretinoin with mental effects like depression, bipolar disorder, schizophrenia, and suicidal ideation, the data are still insufficient and often contradictory. In fact, additional studies with accurate data and larger double-blinded samples, and more analytic systematic reviews are required. It is especially important to monitor the dose and the intervals that isotretinoin has to be administered in order to potentially cause mental health problems, as well as the duration of treatment and the role that the patient's medical and pharmaceutical history may play.Keywords: acne, depression, isotretinoin, mental health
Procedia PDF Downloads 160839 Comparison of Elastic and Viscoelastic Modeling for Asphalt Concrete Surface Layer
Authors: Fouzieh Rouzmehr, Mehdi Mousavi
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Hot mix asphalt concrete (HMAC) is a mixture of aggregates and bitumen. The primary ingredient that determines the mechanical properties of HMAC is the bitumen in it, which displays viscoelastic behavior under normal service conditions. For simplicity, asphalt concrete is considered an elastic material, but this is far from reality at high service temperatures and longer loading times. Viscoelasticity means that the material's stress-strain relationship depends on the strain rate and loading duration. The goal of this paper is to simulate the mechanical response of flexible pavements using linear elastic and viscoelastic modeling of asphalt concrete and predict pavement performance. Falling Weight Deflectometer (FWD) load will be simulated and the results for elastic and viscoelastic modeling will be evaluated. The viscoelastic simulation is performed by the Prony series, which will be modeled by using ANSYS software. Inflexible pavement design, tensile strain at the bottom of the surface layer and compressive strain at the top of the last layer plays an important role in the structural response of the pavement and they will imply the number of loads for fatigue (Nf) and rutting (Nd) respectively. The differences of these two modelings are investigated on fatigue cracking and rutting problem, which are the two main design parameters in flexible pavement design. Although the differences in rutting problem between the two models were negligible, in fatigue cracking, the viscoelastic model results were more accurate. Results indicate that modeling the flexible pavement with elastic material is efficient enough and gives acceptable results.Keywords: flexible pavement, asphalt, FEM, viscoelastic, elastic, ANSYS, modeling
Procedia PDF Downloads 131838 Seismic Activity and Groundwater Behavior at Kalabsha Area, Aswan, Egypt
Authors: S. M. Moustafa, A. Ezzat, Y. S. Taha, G. H. Hassib, S. Hamada
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After the occurrence of 14, Nov, 1981 earthquake (M = 5.3), on Kalabska fault, south of Egypt, seismic stations distributed in and around the Kalabsha area, in order to monitoring, recording and studying the seismic activity in the area. In addition of that, from 1989 a number of piezometer wells drilled in the same area, distribed on at the both side of the active faults area and in different water bearing formations, in order to measuring the groundwater parameters (level, temperature, ph, and conductivity) to monitoring the relationship between those parameters and the seismic activity at Kalabsha area. The behavior of groundwater due to seismic activity over the world studied by several scientists i.e. H. Wakita (1979) on Izu-Oshima earthquake (M= 7.0) at Japan, M. E. Contadakis & G.asteriadis (1972), and Evans (1966), they found an anomalies on groundwater measurements prior, co, and post the occurrence of bigger earthquakes, referring to the probability of precursory evidence of impending earthquakes. In Kalabsha area south of Egypt, this study has been done using recorded seismic data, and the measurements of underground water parameters. same phenomena of anomalies founded on groundwater measurements pre, co. and post the occurrence of earthquakes with magnitude bigger than 3, and no systematic regularity exists for epicenter distance, duration of anomalies or time lag between anomalies appear and occurrence of events. Also the results found present strong relation between the groundwater in the upper unconfined aquifer Nubian Sandstone formation, and Kalabsha seismic activity, otherwise no relation between the seismic activities in the area with the deep groundwater in the lower confined aquifer Sandstone.Keywords: seismicity, groundwater, Aswan, Egypt
Procedia PDF Downloads 381837 Monitoring Synthesis of Biodiesel through Online Density Measurements
Authors: Arnaldo G. de Oliveira, Jr, Matthieu Tubino
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The transesterification process of triglycerides with alcohols that occurs during the biodiesel synthesis causes continuous changes in several physical properties of the reaction mixture, such as refractive index, viscosity and density. Amongst them, density can be an useful parameter to monitor the reaction, in order to predict the composition of the reacting mixture and to verify the conversion of the oil into biodiesel. In this context, a system was constructed in order to continuously determine changes in the density of the reacting mixture containing soybean oil, methanol and sodium methoxide (30 % w/w solution in methanol), stirred at 620 rpm at room temperature (about 27 °C). A polyethylene pipe network connected to a peristaltic pump was used in order to collect the mixture and pump it through a coil fixed on the plate of an analytical balance. The collected mass values were used to trace a curve correlating the mass of the system to the reaction time. The density variation profile versus the time clearly shows three different steps: 1) the dispersion of methanol in oil causes a decrease in the system mass due to the lower alcohol density followed by stabilization; 2) the addition of the catalyst (sodium methoxide) causes a larger decrease in mass compared to the first step (dispersion of methanol in oil) because of the oil conversion into biodiesel; 3) the final stabilization, denoting the end of the reaction. This density variation profile provides information that was used to predict the composition of the mixture over the time and the reaction rate. The precise knowledge of the duration of the synthesis means saving time and resources on a scale production system. This kind of monitoring provides several interesting features such as continuous measurements without collecting aliquots.Keywords: biodiesel, density measurements, online continuous monitoring, synthesis
Procedia PDF Downloads 575836 The Effect of Magnetite Particle Size on Methane Production by Fresh and Degassed Anaerobic Sludge
Authors: E. Al-Essa, R. Bello-Mendoza, D. G. Wareham
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Anaerobic batch experiments were conducted to investigate the effect of magnetite-supplementation (7 mM) on methane production from digested sludge undergoing two different microbial growth phases, namely fresh sludge (exponential growth phase) and degassed sludge (endogenous decay phase). Three different particle sizes were assessed: small (50 - 150 nm), medium (168 – 490 nm) and large (800 nm - 4.5 µm) particles. Results show that, in the case of the fresh sludge, magnetite significantly enhanced the methane production rate (up to 32%) and reduced the lag phase (by 15% - 41%) as compared to the control, regardless of the particle size used. However, the cumulative methane produced at the end of the incubation was comparable in all treatment and control bottles. In the case of the degassed sludge, only the medium-sized magnetite particles increased significantly the methane production rate (12% higher) as compared to the control. Small and large particles had little effect on the methane production rate but did result in an extended lag phase which led to significantly lower cumulative methane production at the end of the incubation period. These results suggest that magnetite produces a clear and positive effect on methane production only when an active and balanced microbial community is present in the anaerobic digester. It is concluded that, (i) the effect of magnetite particle size on increasing the methane production rate and reducing lag phase duration is strongly influenced by the initial metabolic state of the microbial consortium, and (ii) the particle size would positively affect the methane production if it is provided within the nanometer size range.Keywords: anaerobic digestion, iron oxide, methanogenesis, nanoparticle
Procedia PDF Downloads 140835 Systematic Literature Review of Therapeutic Use of Autonomous Sensory Meridian Response (ASMR) and Short-Term ASMR Auditory Training Trial
Authors: Christine H. Cubelo
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This study consists of 2-parts: a systematic review of current publications on the therapeutic use of autonomous sensory meridian response (ASMR) and a within-subjects auditory training trial using ASMR videos. The main intent is to explore ASMR as potentially therapeutically beneficial for those with atypical sensory processing. Many hearing-related disorders and mood or anxiety symptoms overlap with symptoms of sensory processing issues. For this reason, inclusion and exclusion criteria of the systematic review were generated in an effort to produce optimal search outcomes and avoid overly confined criteria that would limit yielded results. Criteria for inclusion in the review for Part 1 are (1) adult participants diagnosed with hearing loss or atypical sensory processing, (2) inclusion of measures related to ASMR as a treatment method, and (3) published between 2000 and 2022. A total of 1,088 publications were found in the preliminary search, and a total of 13 articles met the inclusion criteria. A total of 14 participants completed the trial and post-trial questionnaire. Of all responses, 64.29% agreed that the duration of auditory training sessions was reasonable. In addition, 71.43% agreed that the training improved their perception of music. Lastly, 64.29% agreed that the training improved their perception of a primary talker when there are other talkers or background noises present.Keywords: autonomous sensory meridian response, auditory training, atypical sensory processing, hearing loss, hearing aids
Procedia PDF Downloads 55834 Localization of Geospatial Events and Hoax Prediction in the UFO Database
Authors: Harish Krishnamurthy, Anna Lafontant, Ren Yi
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Unidentified Flying Objects (UFOs) have been an interesting topic for most enthusiasts and hence people all over the United States report such findings online at the National UFO Report Center (NUFORC). Some of these reports are a hoax and among those that seem legitimate, our task is not to establish that these events confirm that they indeed are events related to flying objects from aliens in outer space. Rather, we intend to identify if the report was a hoax as was identified by the UFO database team with their existing curation criterion. However, the database provides a wealth of information that can be exploited to provide various analyses and insights such as social reporting, identifying real-time spatial events and much more. We perform analysis to localize these time-series geospatial events and correlate with known real-time events. This paper does not confirm any legitimacy of alien activity, but rather attempts to gather information from likely legitimate reports of UFOs by studying the online reports. These events happen in geospatial clusters and also are time-based. We look at cluster density and data visualization to search the space of various cluster realizations to decide best probable clusters that provide us information about the proximity of such activity. A random forest classifier is also presented that is used to identify true events and hoax events, using the best possible features available such as region, week, time-period and duration. Lastly, we show the performance of the scheme on various days and correlate with real-time events where one of the UFO reports strongly correlates to a missile test conducted in the United States.Keywords: time-series clustering, feature extraction, hoax prediction, geospatial events
Procedia PDF Downloads 376833 A Study on the Treatment of Municipal Waste Water Using Sequencing Batch Reactor
Authors: Bhaven N. Tandel, Athira Rajeev
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Sequencing batch reactor process is a suspended growth process operating under non-steady state conditions which utilizes a fill and draw reactor with complete mixing during the batch reaction step (after filling) and where the subsequent steps of aeration and clarification occur in the same tank. All sequencing batch reactor systems have five steps in common, which are carried out in sequence as follows, (1) fill (2) react (3) settle (sedimentation/clarification) (4) draw (decant) and (5) idle. The study was carried out in a sequencing batch reactor of dimensions 44cmx30cmx70cm with a working volume of 40 L. Mechanical stirrer of 100 rpm was used to provide continuous mixing in the react period and oxygen was supplied by fish tank aerators. The duration of a complete cycle of sequencing batch reactor was 8 hours. The cycle period was divided into different phases in sequence as follows-0.25 hours fill phase, 6 hours react period, 1 hour settling phase, 0.5 hours decant period and 0.25 hours idle phase. The study consisted of two runs, run 1 and run 2. Run 1 consisted of 6 hours aerobic react period and run 2 consisted of 3 hours aerobic react period followed by 3 hours anoxic react period. The influent wastewater used for the study had COD, BOD, NH3-N and TKN concentrations of 308.03±48.94 mg/L, 100.36±22.05 mg/L, 14.12±1.18 mg/L, and 24.72±2.21 mg/L respectively. Run 1 had an average COD removal efficiency of 41.28%, BOD removal efficiency of 56.25%, NH3-N removal efficiency of 86.19% and TKN removal efficiency of 54.4%. Run 2 had an average COD removal efficiency of 63.19%, BOD removal efficiency of 73.85%, NH3-N removal efficiency of 90.74% and TKN removal efficiency of 65.25%. It was observed that run 2 gave better performance than run 1 in the removal of COD, BOD and TKN.Keywords: municipal waste water, aerobic, anoxic, sequencing batch reactor
Procedia PDF Downloads 550832 MANIFEST-2, a Global, Phase 3, Randomized, Double-Blind, Active-Control Study of Pelabresib (CPI-0610) and Ruxolitinib vs. Placebo and Ruxolitinib in JAK Inhibitor-Naïve Myelofibrosis Patients
Authors: Claire Harrison, Raajit K. Rampal, Vikas Gupta, Srdan Verstovsek, Moshe Talpaz, Jean-Jacques Kiladjian, Ruben Mesa, Andrew Kuykendall, Alessandro Vannucchi, Francesca Palandri, Sebastian Grosicki, Timothy Devos, Eric Jourdan, Marielle J. Wondergem, Haifa Kathrin Al-Ali, Veronika Buxhofer-Ausch, Alberto Alvarez-Larrán, Sanjay Akhani, Rafael Muñoz-Carerras, Yury Sheykin, Gozde Colak, Morgan Harris, John Mascarenhas
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Myelofibrosis (MF) is characterized by bone marrow fibrosis, anemia, splenomegaly and constitutional symptoms. Progressive bone marrow fibrosis results from aberrant megakaryopoeisis and expression of proinflammatory cytokines, both of which are heavily influenced by bromodomain and extraterminal domain (BET)-mediated gene regulation and lead to myeloproliferation and cytopenias. Pelabresib (CPI-0610) is an oral small-molecule investigational inhibitor of BET protein bromodomains currently being developed for the treatment of patients with MF. It is designed to downregulate BET target genes and modify nuclear factor kappa B (NF-κB) signaling. MANIFEST-2 was initiated based on data from Arm 3 of the ongoing Phase 2 MANIFEST study (NCT02158858), which is evaluating the combination of pelabresib and ruxolitinib in Janus kinase inhibitor (JAKi) treatment-naïve patients with MF. Primary endpoint analyses showed splenic and symptom responses in 68% and 56% of 84 enrolled patients, respectively. MANIFEST-2 (NCT04603495) is a global, Phase 3, randomized, double-blind, active-control study of pelabresib and ruxolitinib versus placebo and ruxolitinib in JAKi treatment-naïve patients with primary MF, post-polycythemia vera MF or post-essential thrombocythemia MF. The aim of this study is to evaluate the efficacy and safety of pelabresib in combination with ruxolitinib. Here we report updates from a recent protocol amendment. The MANIFEST-2 study schema is shown in Figure 1. Key eligibility criteria include a Dynamic International Prognostic Scoring System (DIPSS) score of Intermediate-1 or higher, platelet count ≥100 × 10^9/L, spleen volume ≥450 cc by computerized tomography or magnetic resonance imaging, ≥2 symptoms with an average score ≥3 or a Total Symptom Score (TSS) of ≥10 using the Myelofibrosis Symptom Assessment Form v4.0, peripheral blast count <5% and Eastern Cooperative Oncology Group performance status ≤2. Patient randomization will be stratified by DIPSS risk category (Intermediate-1 vs Intermediate-2 vs High), platelet count (>200 × 10^9/L vs 100–200 × 10^9/L) and spleen volume (≥1800 cm^3 vs <1800 cm^3). Double-blind treatment (pelabresib or matching placebo) will be administered once daily for 14 consecutive days, followed by a 7 day break, which is considered one cycle of treatment. Ruxolitinib will be administered twice daily for all 21 days of the cycle. The primary endpoint is SVR35 response (≥35% reduction in spleen volume from baseline) at Week 24, and the key secondary endpoint is TSS50 response (≥50% reduction in TSS from baseline) at Week 24. Other secondary endpoints include safety, pharmacokinetics, changes in bone marrow fibrosis, duration of SVR35 response, duration of TSS50 response, progression-free survival, overall survival, conversion from transfusion dependence to independence and rate of red blood cell transfusion for the first 24 weeks. Study recruitment is ongoing; 400 patients (200 per arm) from North America, Europe, Asia and Australia will be enrolled. The study opened for enrollment in November 2020. MANIFEST-2 was initiated based on data from the ongoing Phase 2 MANIFEST study with the aim of assessing the efficacy and safety of pelabresib and ruxolitinib in JAKi treatment-naïve patients with MF. MANIFEST-2 is currently open for enrollment.Keywords: CPI-0610, JAKi treatment-naïve, MANIFEST-2, myelofibrosis, pelabresib
Procedia PDF Downloads 201831 Honey Intoxication: A Unique Cause of Sudden Cardiac Collapse
Authors: Bharat Rawat, Shekhar Rajbhandari, Yadav Bhatta, Jay Prakash Jaiswal, Shivaji Bikram Silwal, Rajiv Shrestha, Shova Sunuwar
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Introduction: The honey produced by the bees fed on Rhobdodendron species containing grayanotoxin is known as mad honey. Grayanotoxin is found in honey obtained from the nectar of Rhododendron species growing on the mountains of the Black Sea region of Turkey and also in Japan, Nepal, Brazil, parts of North America, and Europe. Although the incidence of grayanotoxin poisoning is rare, there is concern that the number of cases per year will rise with the increasing demand for organic products. Mad honey intoxication might present with mild symptoms of cardiovascular, gastrointestinal and neurological systems or might also present with a life-threatening form with AV block and cardiovascular collapse. In this article, we describe the summary of five cases, which came to our hospital with mad honey related cardiac complications. Findings: In last one year, five cases presented in the emergency department with sudden onset of Loss of consciousness, dizziness, shortness of breath. They felt difficulty after the consumption of 1-3 teaspoonful of wild honey. The honey was brought from most of the rural parts of Nepal like khotang. Some of them also came with vomiting, dizziness, and loose stool. On examination, most of them had severe bradycardia and low blood pressure. No abnormalities were detected on systemic examinations. In one patient, ECG and cardiac enzymes showed features of the acute coronary syndrome, but his treadmill test done few days later was normal. All patients were managed with inj. Atropine, I/V normal saline, and other supportive measures and discharged in a stable condition within one or two days. Conclusions: Rhododendrons is the national flower of Nepal. The specific species of rhododendron found in Nepal which contains the toxin is not known. Bees feeding on these rhododendrons are known to transfer the grayanotoxin to the honey they produce. Most symptoms are mild and resolve themselves without medical intervention. Signs and symptoms of grayanotoxin poisoning rarely last more than 24 hours and are usually not fatal. Some signs of mad honey poisoning include Bradycardia, Cardiac arrhythmia, Hypotension, Nausea and Vomiting. They respond to close monitoring and appropriate supportive treatment. Normally, patients recover completely with no residual damage to the heart or its conduction system.Keywords: rhobdodendron, honey, grayanotoxin, bradycardia
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