Search results for: motility duration
751 Integrated Management of Tithonia Diversifolia in the Vhembe Biosphere Reserve
Authors: Mutavhatsindi Tshinakaho
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Invasive alien plants (IAP’s) are referred to as species that are non-native to the ecosystem under consideration. Whose introduction causes or is likely to cause economic, ecological, or environmental harm. The integrated management of the invasive plant, Tithonia diversifolia, will be assessed through two herbicide trials (one on the seedlings and the other on matured plants) and a competitive trial between Tithonia and invasive grass species. The initial herbicide trial will be undertaken at the University of Venda Agricultural greenhouse facilities, where Tithonia will be planted in pot plants and watered every after two days until they reach at least 30 cm and will then be subjected to four different herbicide treatments (Metsulfuron methyl, Fluroxypyr, Picloram, Triclopyr), water will be utilised as a control. The percentage damage to foliar will be recorded. The second herbicide trial will be undertaken at Levubu road site, where matured Tithonia will be cut at at least 10cm above the ground and the subjected to herbicide treatments (Picloram, Fluroxypyr, Imazapyr, and Water as a control). The site will be visited post treatment for assessment. For the competition trial, tall grass species will be chosen as competitors (Panicum maximum and Eragrostis murvula), they will be grown at six densities per pot in the greenhouse facilities at the University of Venda, were they will be kept watered for the duration of the experiment. At the end of the experiment, plants will be removed from pots, and the above and below ground biomass will be weighed. The expected results are to know the effective integrated management strategy for T. diversifolia, the effective rehabilitation of T. diversifolia invaded habitats, and the effective chemical control of T. diversifoliaKeywords: foliar, biomass, competition, invasion
Procedia PDF Downloads 95750 Psychological Factors Affecting Breastfeeding: An Exploratory Study among Breastfeeding Moms
Authors: Marwa Abdussalam
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Breastfeeding is a unique emotional bond between a mother and their offspring. Though breastfeeding may be natural, it is not something mothers are born with; some still struggle to breastfeed their babies. Various factors can influence the breastfeeding experience, such as the mode of delivery, the mother’s health condition, proper latching, etc. In addition, psychological factors have been known to influence breastfeeding ability, duration, and milk supply. Some mothers struggle to breastfeed their babies because they perceive they have a low milk supply and or don’t have the ability to breastfeed their babies. Most of these perceptions result either from their own past experience or from the ‘comments’ of their caregivers. So, it is of utmost essential to understand such psychological factors affecting breastfeeding so that necessary steps can be taken to educate breastfeeding mothers. The study explored the role of psychological factors that affect breastfeeding. Data were collected from fifteen breastfeeding mothers using a semi-structured interview schedule. A total of 10 questions were included in the interview schedule. Questions were sequenced in a funnel pattern, beginning with open-ended questions and then moving on to close-ended questions. Data were analyzed using Braun and Clarke’s Thematic Analysis technique. This technique involves identifying the codes, generating themes, naming them, and finally reviewing them. Results indicated that breastfeeding self-efficacy perceived insufficient milk supply, and lack of knowledge were the psychological factors affecting breastfeeding. The results of this study can be used to help mothers who are struggling with breastfeeding by developing interventions aimed at improving breastfeeding self-efficacy.Keywords: breastfeeding, breastfeeding self-efficacy, perceived insufficient milk supply, Thematic Analysis
Procedia PDF Downloads 108749 Effect of Silicon on Tritrophic Interaction of Cotton, Whitefly and Chrysoperla carnea
Authors: Asim Abbasi, Muhammad Sufyan
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The present experiment was carried out to examine the effects of silicon dioxide on tritrophic interaction of cotton, whitefly, and the predator Chrysoperla carnea. Population of whitefly was maintained on silicon treated and non-treated cotton for two generations in greenhouse net cages exposed to outside temperature and luminosity. The cotton was treated with silicon dioxide twice after 15 days intervals with 200 ppm concentration. A stock rearing of the natural predator was developed in the laboratory conditions. In the bioassay eggs of the predator all at the same age were individualized in glass petri plates that will be pierced with a pin to allow aeration and maintained in an incubator at 28 ± 2°C, 70 ± 10% relative humidity and 12h photo phase. Population of whitefly stayed on silicon treated, and non-treated cotton were offered to newly hatched chrysopid larvae until the end of the larval stage, assuring a permanent supply. Feeding preference of C. carnea along with longevity, survival of each instar larvae, pupation, adult emergence, and fecundity was checked. The results revealed that there was no significant difference in the feeding preference of C. carnea among both treatments. Durations of 1st and 2nd larval instar were also at par in both treatments. However overall longevity and adult emergence were a bit lower in silicon treated whitefly treatment. This may be due to the fact that silicon reduces the nutritional quality of host because of reduced whitefly feeding on silicon treated cotton. No significant difference in 1st and 2nd larval instars and then increased larval duration in later instars suggested that the effect of silicon treated host should be checked on more than 1 generation of C. carnea to get better findings.Keywords: Chrysoperla carnea, silicon, tritrophic, whitefly
Procedia PDF Downloads 180748 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 273747 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 92746 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 377745 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 515744 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 72743 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 259742 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 635741 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 359740 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 28739 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 85738 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 280737 Resveratrol Ameliorates Benzo(a)Pyrene Induced Testicular Dysfunction and Apoptosis: Involvement of p38 MAPK/ATF2/iNOS Signaling
Authors: Kuladip Jana, Bhaswati Banerjee, Parimal C. Sen
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Benzo(a)pyrene [B(a)P] is an environmental toxicant present mostly in cigarette smoke and car exhaust, is an aryl hydrocarbon receptor (AhR) ligand that exerts its toxic effects on both male and female reproductive systems along with carcinogenesis in skin, prostate, ovary, lung and mammary glands. Our study was focused on elucidating the molecular mechanism of B(a)P induced male reproductive toxicity and its prevention with phytochemical like resveratrol. In this study, the effect of B(a)P at different doses (0.1, 0.25, 0.5, 1 and 5 mg /kg body weight) was studied on male reproductive system of Wistar rat. A significant decrease in cauda epididymal sperm count and motility along with the presence of sperm head abnormalities and altered epididymal and testicular histology were documented following B(a)P treatment. B(a)P treatment resulted apoptotic sperm cells as observed by TUNEL and Annexin V-PI assay with increased Reactive Oxygen Species (ROS), altered sperm mitochondrial membrane potential (ΔΨm) with a simultaneous decrease in the activity of antioxidant enzymes and GSH status. TUNEL positive apoptotic cells also observed in testis as well as isolated germ and Leydig cells following B(a)P exposure. Western Blot analysis revealed the activation of p38 mitogen activated protein kinase (p38MAPK), cytosolic translocation of cytochrome-c, upregulation of Bax and inducible nitric oxide synthase (iNOS) with cleavage of poly ADP ribose polymerase (PARP) and down regulation of BCl2 in testis upon B(a)P treatment. The protein and mRNA levels of testicular key steroidogenesis regulatory proteins like steroidogenic acute regulatory protein (StAR), cytochrome P450 IIA1 (CYPIIA1), 3β hydroxy steroid dehydrogenase (3β HSD), 17β hydroxy steroid dehydrogenase (17β HSD) showed a significant decrease in a dose dependent manner while an increase in the expression of cytochrome P450 1A1 (CYP1A1), Aryl hydrocarbon Receptor (AhR), active caspase- 9 and caspase- 3 following B(a)P exposure. We conclude that exposure of benzo(a)pyrene caused testicular gamatogenic and steroidogenic disorders by induction of oxidative stress, inhibition of StAR and other steroidogenic enzymes along with activation of p38MAPK and initiated caspase-3 mediated germ and Leydig cell apoptosis. Next we investigated the role of resveratrol on B(a)P induced male reproductive toxicity. Our study highlighted that resveratrol co-treatment with B(a)P maintained testicular redox potential, increased serum testosterone level and prevented steroidogenic dysfunction with enhanced expression of major testicular steroidogenic proteins (CYPIIA1, StAR, 3β HSD,17β HSD) relative to treatment with B(a)P only. Resveratrol suppressed B(a)P-induced testicular activation of p38 MAPK, ATF2, iNOS and ROS production; cytosolic translocation of Cytochome c and Caspase 3 activation thereby prevented oxidative stress of testis and inhibited apoptosis. Resveratrol co-treatment also decreased B(a)P-induced AhR protein level, its nuclear translocation and subsequent CYP1A1 promoter activation, thereby decreased protein and mRNA levels of testicular cytochrome P4501A1 (CYP1A1) and prevented BPDE-DNA adduct formation. Our findings cumulatively suggest that resveratrol prevents activation of B(a)P by modulating the transcriptional regulation of CYP1A1 and acting as an antioxidant thus prevents B(a)P-induced oxidative stress and testicular apoptosis.Keywords: benzo(a)pyrene, resveratrol, testis, apoptosis, cytochrome P450 1A1 (CYP1A1), aryl hydrocarbon receptor (AhR), p38 MAPK/ATF2/iNOS
Procedia PDF Downloads 232736 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 319735 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 42734 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 142733 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 173732 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 186731 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 160730 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 131729 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 381728 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 575727 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 140726 Child Feeding Practices Among Mothers in Urban Areas of Akure, Ondo State, Nigeria
Authors: Olufemi Samuel Shola, Oladapo Adenike Adesola
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Inadequate dietary intake has increased the susceptibility of under five children to malnutrition and infections. This study, therefore, assessed the feeding practices of children of 0-23 months of age among mothers in urban areas of Akure, Ondo State, Nigeria. Simple random sampling technique was used to select four hundred (400) mothers out of 710 mothers from 7 primary health care centres in Akure metropolis for the study. Data were collected using modified WHO 2003 Questionnaire on child feeding practices. Data were analyzed using descriptive statistics, while chi-square was used to determine the association between variables. Results showed that 52.0% of the children were males, with 47.5% in the 6-8 months age group. More than half (57.0%) of the mothers were between the ages of 20-29 years, and 45.0% had secondary education. Majority (94.3%) of the mothers breastfed their children in the last 24 hours preceding the survey. The feeding practices history of mothers showed that 28.0% and 53.7% of the mothers initiated breastfeeding less than 30 minutes and between 30 minutes to 1 hour after delivery, respectively. Also, 52.0% of mothers practiced exclusive breastfeeding for six months, while 26.2% breastfed from 6 months up to 2 years of age. Dietary diversity of the children age 6-23 months revealed that 68.7% of the children attained the minimum dietary diversity by consuming 4 or more food groups in the last 24 hours. There was a significant association (P < 0.05) between mothers’ education (n=180), occupation(n=41) and dietary diversity (n= 150) and meal frequency (n=209). Therefore, the study concluded that the duration of breastfeeding and time of introduction of complementary food did not meet WHO recommended guidelines. There is urgent need to launching more programmes.Keywords: breastfeeding, mothers, child feeding, urban areas, ondo state, nigeria
Procedia PDF Downloads 127725 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 55724 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 376723 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 550722 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
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