Search results for: damage criteria
Commenced in January 2007
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Paper Count: 4999

Search results for: damage criteria

469 Spatial Deictics in Face-to-Face Communication: Findings in Baltic Languages

Authors: Gintare Judzentyte

Abstract:

The present research is aimed to discuss semantics and pragmatics of spatial deictics (deictic adverbs of place and demonstrative pronouns) in the Baltic languages: in spoken Lithuanian and in spoken Latvian. The following objectives have been identified to achieve the aim: 1) to determine the usage of adverbs of place in spoken Lithuanian and Latvian and to verify their meanings in face-to-face communication; 2) to determine the usage of demonstrative pronouns in spoken Lithuanian and Latvian and to verify their meanings in face-to-face communication; 3) to compare the systems between the two spoken languages and to identify the main tendencies. As meanings of demonstratives (adverbs of place and demonstrative pronouns) are context-bound, it is necessary to verify their usage in spontaneous interaction. Besides, deictic gestures play a very important role in face-to-face communication. Therefore, an experimental method is necessary to collect the data. Video material representing spoken Lithuanian and spoken Latvian was recorded by means of the method of a qualitative interview (a semi-structured interview: an empirical research is all about asking right questions). The collected material was transcribed and evaluated taking into account several approaches: 1) physical distance (location of the referent, visual accessibility of the referent); 2) deictic gestures (the combination of language and gesture is especially characteristic of the exophoric use); 3) representation of mental spaces in physical space (a speaker sometimes wishes to mark something that is psychically close as psychologically distant and vice versa). The research of the collected data revealed that in face-to-face communication the participants choose deictic adverbs of place instead of demonstrative pronouns to locate/identify entities in situations where the demonstrative pronouns would be expected in spoken Lithuanian and in spoken Latvian. The analysis showed that visual accessibility of the referent is very important in face-to-face communication, but the main criterion while localizing objects and entities is the need for contrast: lith. čia ‘here’, šis ‘this’, latv. šeit ‘here’, šis ‘this’ usually identify distant entities and are used instead of distal demonstratives (lith. ten ‘there’, tas ‘that’, latv. tur ‘there’, tas ‘that’), because the referred objects/subjects contrast to further entities. Furthermore, the interlocutors in examples from a spontaneously situated interaction usually extend their space and can refer to a ‘distal’ object/subject with a ‘proximal’ demonstrative based on the psychological choice. As the research of the spoken Baltic languages confirmed, the choice of spatial deictics in face-to-face communication is strongly effected by a complex of criteria. Although there are some main tendencies, the exact meaning of spatial deictics in the spoken Baltic languages is revealed and is relevant only in a certain context.

Keywords: Baltic languages, face-to-face communication, pragmatics, semantics, spatial deictics

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468 Steel Concrete Composite Bridge: Modelling Approach and Analysis

Authors: Kaviyarasan D., Satish Kumar S. R.

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India being vast in area and population with great scope of international business, roadways and railways network connection within the country is expected to have a big growth. There are numerous rail-cum-road bridges constructed across many major rivers in India and few are getting very old. So there is more possibility of repairing or coming up with such new bridges in India. Analysis and design of such bridges are practiced through conventional procedure and end up with heavy and uneconomical sections. Such heavy class steel bridges when subjected to high seismic shaking has more chance to fail by stability because the members are too much rigid and stocky rather than being flexible to dissipate the energy. This work is the collective study of the researches done in the truss bridge and steel concrete composite truss bridges presenting the method of analysis, tools for numerical and analytical modeling which evaluates its seismic behaviour and collapse mechanisms. To ascertain the inelastic and nonlinear behaviour of the structure, generally at research level static pushover analysis is adopted. Though the static pushover analysis is now extensively used for the framed steel and concrete buildings to study its lateral action behaviour, those findings by pushover analysis done for the buildings cannot directly be used for the bridges as such, because the bridges have completely a different performance requirement, behaviour and typology as compared to that of the buildings. Long span steel bridges are mostly the truss bridges. Truss bridges being formed by many members and connections, the failure of the system does not happen suddenly with single event or failure of one member. Failure usually initiates from one member and progresses gradually to the next member and so on when subjected to further loading. This kind of progressive collapse of the truss bridge structure is dependent on many factors, in which the live load distribution and span to length ratio are most significant. The ultimate collapse is anyhow by the buckling of the compression members only. For regular bridges, single step pushover analysis gives results closer to that of the non-linear dynamic analysis. But for a complicated bridge like heavy class steel bridge or the skewed bridges or complicated dynamic behaviour bridges, nonlinear analysis capturing the progressive yielding and collapse pattern is mandatory. With the knowledge of the postelastic behaviour of the bridge and advancements in the computational facility, the current level of analysis and design of bridges has moved to state of ascertaining the performance levels of the bridges based on the damage caused by seismic shaking. This is because the buildings performance levels deals much with the life safety and collapse prevention levels, whereas the bridges mostly deal with the extent damages and how quick it can be repaired with or without disturbing the traffic after a strong earthquake event. The paper would compile the wide spectrum of modeling to analysis of the steel concrete composite truss bridges in general.

Keywords: bridge engineering, performance based design of steel truss bridge, seismic design of composite bridge, steel-concrete composite bridge

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467 Study of Influencing Factors on the Flowability of Jute Nonwoven Reinforced Sheet Molding Compound

Authors: Miriam I. Lautenschläger, Max H. Scheiwe, Kay A. Weidenmann, Frank Henning, Peter Elsner

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Due to increasing environmental awareness jute fibers are more often used in fiber reinforced composites. In the Sheet Molding Compound (SMC) process, the mold cavity is filled via material flow allowing more complex component design. But, the difficulty of using jute fibers in this process is the decreased capacity of fiber movement in the mold. A comparative flow study with jute nonwoven reinforced SMC was conducted examining the influence of the fiber volume content, the grammage of the jute nonwoven textile and a mechanical modification of the nonwoven textile on the flowability. The nonwoven textile reinforcement was selected to support homogeneous fiber distribution. Trials were performed using two SMC paste formulations differing only in filler type. Platy-shaped kaolin with a mean particle size of 0.8 μm and ashlar calcium carbonate with a mean particle size of 2.7 μm were selected as fillers. Ensuring comparability of the two SMC paste formulations the filler content was determined to reach equal initial viscosity for both systems. The calcium carbonate filled paste was set as reference. The flow study was conducted using a jute nonwoven textile with 300 g/m² as reference. The manufactured SMC sheets were stacked and centrally placed in a square mold. The mold coverage was varied between 25 and 90% keeping the weight of the stack for comparison constant. Comparing the influence of the two fillers kaolin yielded better results regarding a homogeneous fiber distribution. A mold coverage of about 68% was already sufficient to homogeneously fill the mold cavity whereas for calcium carbonate filled system about 79% mold coverage was necessary. The flow study revealed a strong influence of the fiber volume content on the flowability. A fiber volume content of 12 vol.-% and 25 vol.-% were compared for both SMC formulations. The lower fiber volume content strongly supported fiber transport whereas 25 vol.-% showed insignificant influence. The results indicate a limiting fiber volume content for the flowability. The influence of the nonwoven textile grammage was determined using nonwoven jute material with 500 g/m² and a fiber volume content of 20 vol.-%. The 500 g/m² reinforcement material showed inferior results with regard to fiber movement. A mold coverage of about 90 % was required to prevent the destruction of the nonwoven structure. Below this mold coverage the 500 g/m² nonwoven material was ripped and torn apart. Low mold coverages led to damage of the textile reinforcement. Due to the ripped nonwoven structure the textile was modified with cuts in order to facilitate fiber movement in the mold. Parallel cuts of about 20 mm length and 20 mm distance to each other were applied to the textile and stacked with varying orientations prior to molding. Stacks with unidirectional orientated cuts over stacks with cuts in various directions e.g. (0°, 45°, 90°, -45°) were investigated. The mechanical modification supported tearing of the textile without achieving benefit for the flowability.

Keywords: filler, flowability, jute fiber, nonwoven, sheet molding compound

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466 A Mixed Method Approach for Modeling Entry Capacity at Rotary Intersections

Authors: Antonio Pratelli, Lorenzo Brocchini, Reginald Roy Souleyrette

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A rotary is a traffic circle intersection where vehicles entering from branches give priority to circulating flow. Vehicles entering the intersection from converging roads move around the central island and weave out of the circle into their desired exiting branch. This creates merging and diverging conflicts among any entry and its successive exit, i.e., a section. Therefore, rotary capacity models are usually based on the weaving of the different movements in any section of the circle, and the maximum rate of flow value is then related to each weaving section of the rotary. Nevertheless, the single-section capacity value does not lead to the typical performance characteristics of the intersection, such as the entry average delay which is directly linked to its level of service. From another point of view, modern roundabout capacity models are based on the limitation of the flow entering from the single entrance due to the amount of flow circulating in front of the entrance itself. Modern roundabouts capacity models generally lead also to a performance evaluation. This paper aims to incorporate a modern roundabout capacity model into an old rotary capacity method to obtain from the latter the single input capacity and ultimately achieve the related performance indicators. Put simply; the main objective is to calculate the average delay of each single roundabout entrance to apply the most common Highway Capacity Manual, or HCM, criteria. The paper is organized as follows: firstly, the rotary and roundabout capacity models are sketched, and it has made a brief introduction to the model combination technique with some practical instances. The successive section is deserved to summarize the TRRL old rotary capacity model and the most recent HCM-7th modern roundabout capacity model. Then, the two models are combined through an iteration-based algorithm, especially set-up and linked to the concept of roundabout total capacity, i.e., the value reached due to a traffic flow pattern leading to the simultaneous congestion of all roundabout entrances. The solution is the average delay for each entrance of the rotary, by which is estimated its respective level of service. In view of further experimental applications, at this research stage, a collection of existing rotary intersections operating with the priority-to-circle rule has already started, both in the US and in Italy. The rotaries have been selected by direct inspection of aerial photos through a map viewer, namely Google Earth. Each instance has been recorded by location, general urban or rural, and its main geometrical patterns. Finally, conclusion remarks are drawn, and a discussion on some further research developments has opened.

Keywords: mixed methods, old rotary and modern roundabout capacity models, total capacity algorithm, level of service estimation

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465 The Impacts of Export in Stimulating Economic Growth in Ethiopia: ARDL Model Analysis

Authors: Natnael Debalklie Teshome

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The purpose of the study was to empirically investigate the impacts of export performance and its volatility on economic growth in the Ethiopian economy. To do so, time-series data of the sample period from 1974/75 – 2017/18 were collected from databases and annual reports of IMF, WB, NBE, MoFED, UNCTD, and EEA. The extended Cobb-Douglas production function of the neoclassical growth model framed under the endogenous growth theory was used to consider both the performance and instability aspects of export. First, the unit root test was conducted using ADF and PP tests, and data were found in stationery with a mix of I(0) and I(1). Then, the bound test and Wald test were employed, and results showed that there exists long-run co-integration among study variables. All the diagnostic test results also reveal that the model fulfills the criteria of the best-fitted model. Therefore, the ARDL model and VECM were applied to estimate the long-run and short-run parameters, while the Granger causality test was used to test the causality between study variables. The empirical findings of the study reveal that only export and coefficient of variation had significant positive and negative impacts on RGDP in the long run, respectively, while other variables were found to have an insignificant impact on the economic growth of Ethiopia. In the short run, except for gross capital formation and coefficients of variation, which have a highly significant positive impact, all other variables have a strongly significant negative impact on RGDP. This shows exports had a strong, significant impact in both the short-run and long-run periods. However, its positive and statistically significant impact is observed only in the long run. Similarly, there was a highly significant export fluctuation in both periods, while significant commodity concentration (CCI) was observed only in the short run. Moreover, the Granger causality test reveals that unidirectional causality running from export performance to RGDP exists in the long run and from both export and RGDP to CCI in the short run. Therefore, the export-led growth strategy should be sustained and strengthened. In addition, boosting the industrial sector is vital to bring structural transformation. Hence, the government has to give different incentive schemes and supportive measures to exporters to extract the spillover effects of exports. Greater emphasis on price-oriented diversification and specialization on major primary products that the country has a comparative advantage should also be given to reduce value-based instability in the export earnings of the country. The government should also strive to increase capital formation and human capital development via enhancing investments in technology and quality of education to accelerate the economic growth of the country.

Keywords: export, economic growth, export diversification, instability, co-integration, granger causality, Ethiopian economy

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464 Influence of Intra-Yarn Permeability on Mesoscale Permeability of Plain Weave and 3D Fabrics

Authors: Debabrata Adhikari, Mikhail Matveev, Louise Brown, Andy Long, Jan Kočí

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A good understanding of mesoscale permeability of complex architectures in fibrous porous preforms is of particular interest in order to achieve efficient and cost-effective resin impregnation of liquid composite molding (LCM). Fabrics used in structural reinforcements are typically woven or stitched. However, 3D fabric reinforcement is of particular interest because of the versatility in the weaving pattern with the binder yarn and in-plain yarn arrangements to manufacture thick composite parts, overcome the limitation in delamination, improve toughness etc. To predict the permeability based on the available pore spaces between the inter yarn spaces, unit cell-based computational fluid dynamics models have been using the Stokes Darcy model. Typically, the preform consists of an arrangement of yarns with spacing in the order of mm, wherein each yarn consists of thousands of filaments with spacing in the order of μm. The fluid flow during infusion exchanges the mass between the intra and inter yarn channels, meaning there is no dead-end of flow between the mesopore in the inter yarn space and the micropore in the yarn. Several studies have employed the Brinkman equation to take into account the flow through dual-scale porosity reinforcement to estimate their permeability. Furthermore, to reduce the computational effort of dual scale flow, scale separation criteria based on the ratio between yarn permeability to the yarn spacing was also proposed to quantify the dual scale and negligible micro-scale flow regime for the prediction of mesoscale permeability. In the present work, the key parameter to identify the influence of intra yarn permeability on the mesoscale permeability has been investigated with the systematic study of weft and warp yarn spacing on the plane weave as well as the position of binder yarn and number of in-plane yarn layers on 3D weave fabric. The permeability tensor has been estimated using an OpenFOAM-based model for the various weave pattern with idealized geometry of yarn implemented using open-source software TexGen. Additionally, scale separation criterion has been established based on the various configuration of yarn permeability for the 3D fabric with both the isotropic and anisotropic yarn from Gebart’s model. It was observed that the variation of mesoscale permeability Kxx within 30% when the isotropic porous yarn is considered for a 3D fabric with binder yarn. Furthermore, the permeability model developed in this study will be used for multi-objective optimizations of the preform mesoscale geometry in terms of yarn spacing, binder pattern, and a number of layers with an aim to obtain improved permeability and reduced void content during the LCM process.

Keywords: permeability, 3D fabric, dual-scale flow, liquid composite molding

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463 Investigation of Ground Disturbance Caused by Pile Driving: Case Study

Authors: Thayalan Nall, Harry Poulos

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Piling is the most widely used foundation method for heavy structures in poor soil conditions. The geotechnical engineer can choose among a variety of piling methods, but in most cases, driving piles by impact hammer is the most cost-effective alternative. Under unfavourable conditions, driving piles can cause environmental problems, such as noise, ground movements and vibrations, with the risk of ground disturbance leading to potential damage to proposed structures. In one of the project sites in which the authors were involved, three offshore container terminals, namely CT1, CT2 and CT3, were constructed over thick compressible marine mud. The seabed was around 6m deep and the soft clay thickness within the project site varied between 9m and 20m. CT2 and CT3 were connected together and rectangular in shape and were 2600mx800m in size. CT1 was 400m x 800m in size and was located on south opposite of CT2 towards its eastern end. CT1 was constructed first and due to time and environmental limitations, it was supported on a “forest” of large diameter driven piles. CT2 and CT3 are now under construction and are being carried out using a traditional dredging and reclamation approach with ground improvement by surcharging with vertical drains. A few months after the installation of the CT1 piles, a 2600m long sand bund to 2m above mean sea level was constructed along the southern perimeter of CT2 and CT3 to contain the dredged mud that was expected to be pumped. The sand bund was constructed by sand spraying and pumping using a dredging vessel. About 2000m length of the sand bund in the west section was constructed without any major stability issues or any noticeable distress. However, as the sand bund approached the section parallel to CT1, it underwent a series of deep seated failures leading the displaced soft clay materials to heave above the standing water level. The crest of the sand bund was about 100m away from the last row of piles. There were no plausible geological reasons to conclude that the marine mud only across the CT1 region was weaker than over the rest of the site. Hence it was suspected that the pile driving by impact hammer may have caused ground movements and vibrations, leading to generation of excess pore pressures and cyclic softening of the marine mud. This paper investigates the probable cause of failure by reviewing: (1) All ground investigation data within the region; (2) Soil displacement caused by pile driving, using theories similar to spherical cavity expansion; (3) Transfer of stresses and vibrations through the entire system, including vibrations transmitted from the hammer to the pile, and the dynamic properties of the soil; and (4) Generation of excess pore pressure due to ground vibration and resulting cyclic softening. The evidence suggests that the problems encountered at the site were primarily caused by the “side effects” of the pile driving operations.

Keywords: pile driving, ground vibration, excess pore pressure, cyclic softening

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462 Analyzing the Use of Augmented and Virtual Reality to Teach Social Skills to Students with Autism

Authors: Maggie Mosher, Adam Carreon, Sean Smith

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A systematic literature review was conducted to explore the evidence base on the use of augmented reality (AR), virtual reality (VR), mixed reality (MR), and extended reality (XR) to present social skill instruction to school-age students with autism spectrum disorder (ASD). Specifically, the systematic review focus was on a. the participants and intervention agents using AR, VR, MR, and XR for social skill acquisition b. the social skills taught through these mediums and c. the social validity measures (i.e., goals, procedures, and outcomes) reported in these studies. Forty-one articles met the inclusion criteria. Researchers in six studies taught social skills to students through AR, in 27 studies through non-immersive VR, and in 10 studies through immersive VR. No studies used MR or XR. The primary targeted social skills were relationship skills, emotion recognition, social awareness, cooperation, and executive functioning. An intervention to improve many social skills was implemented by 73% of researchers, 17% taught a single skill, and 10% did not clearly state the targeted skill. The intervention was considered effective in 26 of the 41 studies (63%), not effective in four studies (10%), and 11 studies (27%) reported mixed results. No researchers reported information for all 17 social validity indicators. The social validity indicators reported by researchers ranged from two to 14. Social validity measures on the feelings toward and use of the technology were provided in 22 studies (54%). Findings indicated both AR and VR are promising platforms for providing social skill instruction to students with ASD. Studies utilizing this technology show a number of social validity indicators. However, the limited information provided on the various interventions, participant characteristics, and validity measures, offers insufficient evidence of the impact of these technologies in teaching social skills to students with ASD. Future research should develop a protocol for training treatment agents to assess the role of different variables (i.e., whether agents are customizing content, monitoring student learning, using intervention specific vocabulary in their day to day instruction). Sustainability may be increased by providing training in the technology to both treatment agents and participants. Providing scripts of instruction occurring within the intervention would provide the needed information to determine the primary method of teaching within the intervention. These variables play a role in maintenance and generalization of the social skills. Understanding the type of feedback provided would help researchers determine if students were able to feel rewarded for progressing through the scenarios or if students require rewarding aspects within the intervention (i.e., badges, trophies). AR has the potential to generalize instruction and VR has the potential for providing a practice environment for performance deficits. Combining these two technologies into a mixed reality intervention may provide a more cohesive and effective intervention.

Keywords: autism, augmented reality, social and emotional learning, social skills, virtual reality

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461 The Effect of Metal-Organic Framework Pore Size to Hydrogen Generation of Ammonia Borane via Nanoconfinement

Authors: Jing-Yang Chung, Chi-Wei Liao, Jing Li, Bor Kae Chang, Cheng-Yu Wang

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Chemical hydride ammonia borane (AB, NH3BH3) draws attentions to hydrogen energy researches for its high theoretical gravimetrical capacity (19.6 wt%). Nevertheless, the elevated AB decomposition temperatures (Td) and unwanted byproducts are main hurdles in practical application. It was reported that the byproducts and Td can be reduced with nanoconfinement technique, in which AB molecules are confined in porous materials, such as porous carbon, zeolite, metal-organic frameworks (MOFs), etc. Although nanoconfinement empirically shows effectiveness on hydrogen generation temperature reduction in AB, the theoretical mechanism is debatable. Low Td was reported in AB@IRMOF-1 (Zn4O(BDC)3, BDC = benzenedicarboxylate), where Zn atoms form closed metal clusters secondary building unit (SBU) with no exposed active sites. Other than nanosized hydride, it was also observed that catalyst addition facilitates AB decomposition in the composite of Li-catalyzed carbon CMK-3, MOF JUC-32-Y with exposed Y3+, etc. It is believed that nanosized AB is critical for lowering Td, while active sites eliminate byproducts. Nonetheless, some researchers claimed that it is the catalytic sites that are the critical factor to reduce Td, instead of the hydride size. The group physically ground AB with ZIF-8 (zeolitic imidazolate frameworks, (Zn(2-methylimidazolate)2)), and found similar reduced Td phenomenon, even though AB molecules were not ‘confined’ or forming nanoparticles by physical hand grinding. It shows the catalytic reaction, not nanoconfinement, leads to AB dehydrogenation promotion. In this research, we explored the possible criteria of hydrogen production temperature from nanoconfined AB in MOFs with different pore sizes and active sites. MOFs with metal SBU such as Zn (IRMOF), Zr (UiO), and Al (MIL-53), accompanying with various organic ligands (BDC and BPDC; BPDC = biphenyldicarboxylate) were modified with AB. Excess MOFs were used for AB size constrained in micropores estimated by revisiting Horvath-Kawazoe model. AB dissolved in methanol was added to MOFs crystalline with MOF pore volume to AB ratio 4:1, and the slurry was dried under vacuum to collect AB@MOF powders. With TPD-MS (temperature programmed desorption with mass spectroscopy), we observed Td was reduced with smaller MOF pores. For example, it was reduced from 100°C to 64°C when MOF micropore ~1 nm, while ~90°C with pore size up to 5 nm. The behavior of Td as a function of AB crystalline radius obeys thermodynamics when the Gibbs free energy of AB decomposition is zero, and no obvious correlation with metal type was observed. In conclusion, we discovered Td of AB is proportional to the reciprocal of MOF pore size, possibly stronger than the effect of active sites.

Keywords: ammonia borane, chemical hydride, metal-organic framework, nanoconfinement

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460 Kawasaki Disease in a Two Months Kuwaiti Girl: A Case Report ‎and Literature Review.‎

Authors: Hanan Bin Nakhi, Asaad M. Albadrawi, Maged Al Shahat, ‎Entesar Mandani

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Background:‎ Kawasaki disease (KD) is one of the most common vasculitis of childhood. ‎It is considered the leading cause of acquired heart disease in children. The ‎peak age of occurrence is 6 to 24 months, with 80% of affected children being ‎less than 5 years old. There are only a few reports of KD in infants younger ‎than 6 months. Infants had a higher incidence of atypical KD and of coronary ‎artery complications. This case report from Kuwait will reinforce considering ‎atypical KD in case of sepsis like condition with negative cultures and ‎unresponding to systemic antibiotics. Early diagnosis allows early treatment ‎with intravenous immune globulin (IVIG) and so decreases the incidence of ‎cardiac aneurysm.‎ Case Report:‎ A 2 month old female infant, product of full term normal delivery to ‎consanguineous parents, presented with fever and poor feeding. She was ‎admitted and treated as urinary tract infection as her urine routine revealed ‎pyurea. The baby continued to have persistent fever and hypoactivity inspite ‎of using intravenous antibiotics. Latter, she developed non purulent ‎conjunctivitis, skin mottling, oedema of the face / lower limb and was treated ‎in intensive care unit as a case of septic shock. In spite of her partial general ‎improvement, she continued to look unwell, hypoactive and had persistent ‎fever. Septic work up, metabolic, and immunologic screen were negative. KD ‎was suspected when the baby developed polymorphic erythematous rash and ‎noticed to have peeling of skin at perianal area and periangular area of the ‎fingers of the hand and feet. IVIG was given in dose of 2 gm/kg/day in single ‎dose and aspirin 100 mg/kg/day in four divided doses. The girl showed marked ‎clinical improvement. The fever subsided dramatically and the level acute ‎phase reactant markedly decreased but the platelets count increased to ‎‎1600000/mm3. Echo cardiography showed mild dilatation of mid right ‎coronary artery. Aspirin was continued in a dose of 5 mg/kg/d till repeating ‎cardiac echo. ‎Conclusion:‎ A high index of suspicion of KD must be maintained in young infants with ‎prolonged unexplained fever. Accepted criteria should be less restrictive to ‎allow early diagnosis of a typical KD in infants less than 6 months of age. ‎Timely appropriate treatment with IVIG is essential to avoid severe coronary ‎sequels.‎

Keywords: Kawasaki disease, atypical Kawasaki disease, infantile Kawasaki disease, hypo activity‎ ‎

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459 Muscle and Cerebral Regional Oxygenation in Preterm Infants with Shock Using Near-Infrared Spectroscopy

Authors: Virany Diana, Martono Tri Utomo, Risa Etika

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Background: Shock is one severe condition that can be a major cause of morbidity and mortality in the Neonatal Intensive Care Unit. Preterm infants are very susceptible to shock caused by many complications such as asphyxia, patent ductus arteriosus, intra ventricle haemorrhage, necrotizing enterocolitis, persistent pulmonal hypertension of the newborn, and septicaemia. Limited hemodynamic monitoring for early detection of shock causes delayed intervention and comprises the outcomes. Clinical parameters still used in neonatal shock detection, such as Capillary Refill Time, heart rate, cold extremity, and urine production. Blood pressure is most frequently used to evaluate preterm's circulation, but hypotension indicates uncompensated shock. Near-infrared spectroscopy (NIRS) is known as a noninvasive tool for monitoring and detecting the state of inadequate tissue perfusion. Muscle oxygen saturation shows decreased cardiac output earlier than systemic parameters of tissue oxygenation when cerebral regional oxygen saturation is still stabilized by autoregulation. However, to our best knowledge, until now, no study has analyzed the decrease of muscle oxygen regional saturation (mRSO₂) and the ratio of muscle and cerebral oxygen regional saturation (mRSO₂/cRSO₂) by NIRS in preterm with shock. Purpose: The purpose of this study is to analyze the decrease of mRSO₂ and ratio of muscle to cerebral oxygen regional saturation (mRSO₂/cRSO₂) by NIRS in preterm with shock. Patients and Methods: This cross-sectional study was conducted on preterm infants with 28-34 weeks gestational age, admitted to the NICU of Dr. Soetomo Hospital from November to January 2022. Patients were classified into two groups: shock and non-shock. The diagnosis of shock is based on clinical criteria (tachycardia, prolonged CRT, cold extremity, decreased urine production, and MAP Blood Pressure less than GA in weeks). Measurement of mRSO₂ and cRSO₂ by NIRS was performed by the doctor in charge when the patient came to NICU. Results: We enrolled 40 preterm infants. The initial conventional hemodynamic parameter as the basic diagnosis of shock showed significant differences in all variables. Preterm with shock had higher mean HR (186.45±1.5), lower MAP (29.8±2.1), and lower SBP (45.1±4.28) than non-shock children, and most had a prolonged CRT. The patients’ outcome was not a significant difference between shock and non-shock patients. The mean mRSO₂ in the shock and non-shock groups were 33,65 ± 11,32 vs. 69,15 ± 3,96 (p=0.001), and the mean ratio mRSO₂/cRSO₂ 0,45 ± 0,12 vs. 0,84 ± 0,43 (p=0,001), were significantly different. The mean cRSO₂ in the shock and non-shock groups were 71,60 ± 4,90 vs. 81,85 ± 7,85 (p 0.082), not significantly different. Conclusion: The decrease of mRSO₂ and ratio of mRSO₂/cRSO₂ can differentiate between shock and non-shock in the preterm infant when cRSO₂ is still normal.

Keywords: preterm infant, regional muscle oxygen saturation, regional cerebral oxygen saturation, NIRS, shock

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458 Development and Obtaining of Solid Dispersions to Increase the Solubility of Efavirenz in Anti-HIV Therapy

Authors: Salvana P. M. Costa, Tarcyla A. Gomes, Giovanna C. R. M. Schver, Leslie R. M. Ferraz, Cristovão R. Silva, Magaly A. M. Lyra, Danilo A. F. Fonte, Larissa A. Rolim, Amanda C. Q. M. Vieira, Miracy M. Albuquerque, Pedro J. Rolim-neto

Abstract:

Efavirenz (EFV) is considered one of the most widely used anti-HIV drugs. However, it is classified as a drug class II (poorly soluble, highly permeable) according to the biopharmaceutical classification system, presenting problems of absorption in the gastrointestinal tract and thereby inadequate bioavailability for its therapeutic action. This study aimed to overcome these barriers by developing and obtaining solid dispersions (SD) in order to increase the EFZ bioavailability. For the development of SD with EFV, theoretical and practical studies were initially performed. Thus, there was a choice of a carrier to be used. For this, it was analyzed the various criteria such as glass transition temperature of the polymer, intra- and intermolecular interactions of hydrogen bonds between drug and polymer, the miscibility between the polymer and EFV. The choice of the obtainment method of the SD came from the analysis of which method is the most consolidated in both industry and literature. Subsequently, the choice of drug and carrier concentrations in the dispersions was carried out. In order to obtain DS to present the drug in its amorphous form, as the DS were obtained, they were analyzed by X-ray diffraction (XRD). SD are more stable the higher the amount of polymer present in the formulation. With this assumption, a SD containing 10% of drug was initially prepared and then this proportion was increased until the XRD showed the presence of EFV in its crystalline form. From this point, it was not produced SD with a higher concentration of drug. Thus, it was allowed to select PVP-K30, PVPVA 64 and the SOLUPLUS formulation as carriers, once it was possible the formation of hydrogen bond between EFV and polymers since these have hydrogen acceptor groups capable of interacting with the donor group of the drug hydrogen. It is worth mentioning also that the films obtained, independent of concentration used, were presented homogeneous and transparent. Thus, it can be said that the EFV is miscible in the three polymers used in the study. The SD and Physical Mixtures (PM) with these polymers were prepared by the solvent method. The EFV diffraction profile showed main peaks at around 2θ of 6,24°, in addition to other minor peaks at 14,34°, 17,08°, 20,3°, 21,36° and 25,06°, evidencing its crystalline character. Furthermore, the polymers showed amorphous nature, as evidenced by the absence of peaks in their XRD patterns. The XRD patterns showed the PM overlapping profile of the drug with the polymer, indicating the presence of EFV in its crystalline form. Regardless the proportion of drug used in SD, all the samples showed the same characteristics with no diffraction peaks EFV, demonstrating the behavior amorphous products. Thus, the polymers enabled, effectively, the formation of amorphous SD, probably due to the potential hydrogen bonds between them and the drug. Moreover, the XRD analysis showed that the polymers were able to maintain its amorphous form in a concentration of up to 80% drug.

Keywords: amorphous form, Efavirenz, solid dispersions, solubility

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457 Evaluating the Effect of 'Terroir' on Volatile Composition of Red Wines

Authors: María Luisa Gonzalez-SanJose, Mihaela Mihnea, Vicente Gomez-Miguel

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The zoning methodology currently recommended by the OIVV as official methodology to carry out viticulture zoning studies and to define and delimit the ‘terroirs’ has been applied in this study. This methodology has been successfully applied on the most significant an important Spanish Oenological D.O. regions, such as Ribera de Duero, Rioja, Rueda and Toro, but also it have been applied around the world in Portugal, different countries of South America, and so on. This is a complex methodology that uses edaphoclimatic data but also other corresponding to vineyards and other soils’ uses The methodology is useful to determine Homogeneous Soil Units (HSU) to different scale depending on the interest of each study, and has been applied from viticulture regions to particular vineyards. It seems that this methodology is an appropriate method to delimit correctly the medium in order to enhance its uses and to obtain the best viticulture and oenological products. The present work is focused on the comparison of volatile composition of wines made from grapes grown in different HSU that coexist in a particular viticulture region of Castile-Lion cited near to Burgos. Three different HSU were selected for this study. They represented around of 50% of the global area of vineyards of the studied region. Five different vineyards on each HSU under study were chosen. To reduce variability factors, other criteria were also considered as grape variety, clone, rootstocks, vineyard’s age, training systems and cultural practices. This study was carried out during three consecutive years, then wine from three different vintage were made and analysed. Different red wines were made from grapes harvested in the different vineyards under study. Grapes were harvested to ‘Technological maturity’, which are correlated with adequate levels of sugar, acidity, phenolic content (nowadays named phenolic maturity), good sanitary stages and adequate levels of aroma precursors. Results of the volatile profile of the wines produced from grapes of each HSU showed significant differences among them pointing out a direct effect of the edaphoclimatic characteristic of each UHT on the composition of the grapes and then on the volatile composition of the wines. Variability induced by HSU co-existed with the well-known inter-annual variability correlated mainly with the specific climatic conditions of each vintage, however was most intense, so the wine of each HSU were perfectly differenced. A discriminant analysis allowed to define the volatiles with discriminant capacities which were 21 of the 74 volatiles analysed. Detected discriminant volatiles were chemical different, although .most of them were esters, followed by were superior alcohols and fatty acid of short chain. Only one lactone and two aldehydes were selected as discriminant variable, and no varietal aroma compounds were selected, which agree with the fact that all the wine were made from the same grape variety.

Keywords: viticulture zoning, terroir, wine, volatile profile

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456 Growth and Bone Health in Children following Liver Transplantation

Authors: Faris Alkhalil, Rana Bitar, Amer Azaz, Hisham Natour, Noora Almeraikhi, Mohamad Miqdady

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Background: Children with liver transplantation are achieving very good survival and so there is now a need to concentrate on achieving good health in these patients and preventing disease. Immunosuppressive medications have side effects that need to be monitored and if possible avoided. Glucocorticoids and calcineurin inhibitors are detrimental to bone and mineral homeostasis in addition steroids can also affect linear growth. Steroid sparing regimes in renal transplant children has shown to improve children’s height. Aim: We aim to review the growth and bone health of children post liver transplant by measuring bone mineral density (BMD) using dual energy X-ray absorptiometry (DEXA) scan and assessing if there is a clear link between poor growth and impaired bone health and use of long term steroids. Subjects and Methods: This is a single centre retrospective Cohort study, we reviewed the medical notes of children (0-16 years) who underwent a liver transplantation between November 2000 to November 2016 and currently being followed at our centre. Results: 39 patients were identified (25 males and 14 females), the median transplant age was 2 years (range 9 months - 16 years), and the median follow up was 6 years. Four patients received a combined transplant, 2 kidney and liver transplant and 2 received a liver and small bowel transplant. The indications for transplant included, Biliary Atresia (31%), Acute Liver failure (18%), Progressive Familial Intrahepatic Cholestasis (15%), transplantable metabolic disease (10%), TPN related liver disease (8%), Primary Hyperoxaluria (5%), Hepatocellular carcinoma (3%) and other causes (10%). 36 patients (95%) were on a calcineurin inhibitor (34 patients were on Tacrolimus and 2 on Cyclosporin). The other three patients were on Sirolimus. Low dose long-term steroids was used in 21% of the patients. A considerable proportion of the patients had poor growth. 15% were below the 3rd centile for weight for age and 21% were below the 3rd centile for height for age. Most of our patients with poor growth were not on long term steroids. 49% of patients had a DEXA scan post transplantation. 21% of these children had low bone mineral density, one patient had met osteoporosis criteria with a vertebral fracture. Most of our patients with impaired bone health were not on long term steroids. 20% of the patients who did not undergo a DEXA scan developed long bone fractures and 50% of them were on long term steroid use which may suggest impaired bone health in these patients. Summary and Conclusion: The incidence of impaired bone health, although studied in limited number of patients; was high. Early recognition and treatment should be instituted to avoid fractures and improve bone health. Many of the patients were below the 3rd centile for weight and height however there was no clear relationship between steroid use and impaired bone health, reduced weight and reduced linear height.

Keywords: bone, growth, pediatric, liver, transplantation

Procedia PDF Downloads 275
455 A Systematic Review of Chronic Neurologic Complications of COVID-19; A Potential Risk Factor for Narcolepsy, Parkinson's Disease, and Multiple Sclerosis.

Authors: Sulemana Saibu, Moses Ikpeme

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Background: The severity of the COVID-19 pandemic, brought on by the SARS-CoV-2 coronavirus, has been unprecedented since the 1918 influenza pandemic. SARS-CoV-2 cases of CNS and peripheral nervous system disease, including neurodegenerative disorders and chronic immune-mediated diseases, may be anticipated based on knowledge of past coronaviruses, particularly those that caused the severe acute respiratory syndrome and Middle East respiratory syndrome outbreaks. Although respiratory symptoms are the most common clinical presentation, neurological symptoms are becoming increasingly recognized, raising concerns about their potential role in causing Parkinson's disease, Multiple sclerosis, and Narcolepsy. This systematic review aims to summarize the current evidence by exploring the association between COVID-19 infection and how it may overlap with etiological mechanisms resulting in Narcolepsy, Parkinson's disease, and Multiple sclerosis. Methods: A systematic search was conducted using electronic databases ((PubMed/MedLine, Embase, PsycINFO, ScieLO, Web of Science, ProQuest (Biotechnology, Virology, and AIDS), Scopus, and CINAHL)) to identify studies published between January 2020 and December 2022 that investigated the association between COVID-19 and Parkinson's disease, multiple sclerosis, and Narcolepsy. Per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the review was performed and reported. Study quality was assessed using the Critical Appraisal Skills Programme Checklist and the Joanna Briggs Institute Critical appraisal tools. Results: A total of 21 studies out of 1025 met the inclusion criteria, including 8 studies reporting Parkinson's disease, 11 on multiple sclerosis, and 2 on Narcolepsy. In COVID-19 individuals compared to the general population, Narcolepsy, Parkinson's disease, and multiple sclerosis were shown to have a higher incidence. The findings imply that COVID-19 may worsen the signs or induce multiple sclerosis and Parkinson's disease and may raise the risk of developing Narcolepsy. Further research is required to confirm these connections because the available data is insufficient. Conclusion: According to the existing data, COVID-19 may raise the risk of Narcolepsy and have a causative relationship with Parkinson's disease, multiple sclerosis, and other diseases. More study is required to confirm these correlations and pinpoint probable mechanisms behind these interactions. Clinicians should be aware of how COVID-19 may affect various neurological illnesses and should treat patients who are affected accordingly.

Keywords: COVID-19, parkinson’s disease, multiple sclerosis, narcolepsy, neurological disorders, sars-cov-2, neurodegenerative disorders, chronic immune-mediated diseases

Procedia PDF Downloads 81
454 Effect of Fresh Concrete Curing Methods on Its Compressive Strength

Authors: Xianghe Dai, Dennis Lam, Therese Sheehan, Naveed Rehman, Jie Yang

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Concrete is one of the most used construction materials that may be made onsite as fresh concrete and then placed in formwork to produce the desired shapes of structures. It has been recognized that the raw materials and mix proportion of concrete dominate the mechanical characteristics of hardened concrete, and the curing method and environment applied to the concrete in early stages of hardening will significantly influence the concrete properties, such as compressive strength, durability, permeability etc. In construction practice, there are various curing methods to maintain the presence of mixing water throughout the early stages of concrete hardening. They are also beneficial to concrete in hot weather conditions as they provide cooling and prevent the evaporation of water. Such methods include ponding or immersion, spraying or fogging, saturated wet covering etc. Also there are various curing methods that may be implemented to decrease the level of water lost which belongs to the concrete surface, such as putting a layer of impervious paper, plastic sheeting or membrane on the concrete to cover it. In the concrete material laboratory, accelerated strength gain methods supply the concrete with heat and additional moisture by applying live steam, coils that are subject to heating or pads that have been warmed electrically. Currently when determining the mechanical parameters of a concrete, the concrete is usually sampled from fresh concrete on site and then cured and tested in laboratories where standardized curing procedures are adopted. However, in engineering practice, curing procedures in the construction sites after the placing of concrete might be very different from the laboratory criteria, and this includes some standard curing procedures adopted in the laboratory that can’t be applied on site. Sometimes the contractor compromises the curing methods in order to reduce construction costs etc. Obviously the difference between curing procedures adopted in the laboratory and those used on construction sites might over- or under-estimate the real concrete quality. This paper presents the effect of three typical curing methods (air curing, water immersion curing, plastic film curing) and of maintaining concrete in steel moulds on the compressive strength development of normal concrete. In this study, Portland cement with 30% fly ash was used and different curing periods, 7 days, 28 days and 60 days were applied. It was found that the highest compressive strength was observed from concrete samples to which 7-day water immersion curing was applied and from samples maintained in steel moulds up to the testing date. The research results implied that concrete used as infill in steel tubular members might develop a higher strength than predicted by design assumptions based on air curing methods. Wrapping concrete with plastic film as a curing method might delay the concrete strength development in the early stages. Water immersion curing for 7 days might significantly increase the concrete compressive strength.

Keywords: compressive strength, air curing, water immersion curing, plastic film curing, maintaining in steel mould, comparison

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453 Assessing the High Rate of Deforestation Caused by the Operations of Timber Industries in Ghana

Authors: Obed Asamoah

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Forests are very vital for human survival and our well-being. During the past years, the world has taken an increasingly significant role in the modification of the global environment. The high rate of deforestation in Ghana is of primary national concern as the forests provide many ecosystem services and functions that support the country’s predominantly agrarian economy and foreign earnings. Ghana forest is currently major source of carbon sink that helps to mitigate climate change. Ghana forests, both the reserves and off-reserves, are under pressure of deforestation. The causes of deforestation are varied but can broadly be categorized into anthropogenic and natural factors. For the anthropogenic factors, increased wood fuel collection, clearing of forests for agriculture, illegal and poorly regulated timber extraction, social and environmental conflicts, increasing urbanization and industrialization are the primary known causes for the loss of forests and woodlands. Mineral exploitation in the forest areas is considered as one of the major causes of deforestation in Ghana. Mining activities especially mining of gold by both the licensed mining companies and illegal mining groups who are locally known as "gallantly mining" also cause damage to the nation's forest reserves. Several works have been conducted regarding the causes of the high rate of deforestation in Ghana, major attention has been placed on illegal logging and using forest lands for illegal farming and mining activities. Less emphasis has been placed on the timber production companies on their harvesting methods in the forests in Ghana and other activities that are carried out in the forest. The main objective of the work is to find out the harvesting methods and the activities of the timber production companies and their effects on the forests in Ghana. Both qualitative and quantitative research methods were engaged in the research work. The study population comprised of 20 Timber industries (Sawmills) forest areas of Ghana. These companies were selected randomly. The cluster sampling technique was engaged in selecting the respondents. Both primary and secondary data were employed. In the study, it was observed that most of the timber production companies do not know the age, the weight, the distance covered from the harvesting to the loading site in the forest. It was also observed that old and heavy machines are used by timber production companies in their operations in the forest, which makes the soil compact prevents regeneration and enhances soil erosion. It was observed that timber production companies do not abide by the rules and regulations governing their operations in the forest. The high rate of corruption on the side of the officials of the Ghana forestry commission makes the officials relax and do not embark on proper monitoring on the operations of the timber production companies which makes the timber companies to cause more harm to the forest. In other to curb this situation the Ghana forestry commission with the ministry of lands and natural resources should monitor the activities of the timber production companies and sanction all the companies that make foul play in their activities in the forest. The commission should also pay more attention to the policy “fell one plant 10” to enhance regeneration in both reserves and off-reserves forest.

Keywords: companies, deforestation, forest, Ghana, timber

Procedia PDF Downloads 193
452 A Preliminary Randomized Controlled Trial of Pure L-Ascorbic Acid with Using a Needle-Free and Micro-Needle Mesotherapy in Treatment of Anti-Aging Procedure

Authors: M. Zasada, A. Markiewicz, A. Erkiert-Polguj, E. Budzisz

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The epidermis is a keratinized stratified squamous epithelium covered by the hydro-lipid barrier. Therefore, active substances should be able to penetrate through this hydro-lipid coating. L-ascorbic acid is one of the vitamins which plays an important role in stimulation fibroblast to produce collagen type I and in hyperpigmentation lightening. Vitamin C is a water-soluble antioxidant, which protects skin from oxidation damage and rejuvenates photoaged skin. No-needle mesotherapy is a non-invasive rejuvenation technique depending on electric pulses, electroporation, and ultrasounds. These physicals factors result in deeper penetration of cosmetics. It is important to increase the penetration of L-ascorbic acid, thereby increasing the spectrum of its activity. The aim of the work was to assess the effectiveness of pure L-ascorbic acid activity in anti-aging therapy using a needle-free and micro-needling mesotherapy. The study was performed on a group of 35 healthy volunteers in accordance with the Declaration of Helsinki of 1964 and agreement of the Ethics Commissions no RNN/281/16/KE 2017. Women were randomized to mesotherapy or control group. Control group applied topically 2,5 ml serum containing 20% L-ascorbic acid with hydrate from strawberries, every 10 days for a period of 9 weeks. No-needle mesotherapy, on the left half of the face and micro-needling on the right with the same serum, was done in mesotherapy group. The pH of serum was 3.5-4, and the serum was prepared directly prior to the facial treatment. The skin parameters were measured at the beginning and before each treatment. The measurement of the forehead skin was done using Cutometer® (measurement of skin elasticity and firmness), Corneometer® (skin hydration measurement), Mexameter® (skin tone measurement). Also, the photographs were taken by Fotomedicus system. Additionally, the volunteers fulfilled the questionnaire. Serum was tested for microbiological purity and stability after the opening of the cosmetic. During the study, all of the volunteers were taken care of a dermatologist. The regular application of the serum has caused improvement of the skin parameters. Respectively, after 4 and 8 weeks improvement in hydration and elasticity has been seen (Corneometer®, Cutometer® results). Moreover, the number of hyper-pigmentated spots has decreased (Mexameter®). After 8 weeks the volunteers has claimed that the tested product has smoothing and moisturizing features. Subjective opinions indicted significant improvement of skin color and elasticity. The product containing the L-ascorbic acid used with intercellular penetration promoters demonstrates higher anti-aging efficiency than control. In vivo studies confirmed the effectiveness of serum and the impact of the active substance on skin firmness and elasticity, the degree of hydration and skin tone. Mesotherapy with pure L-ascorbic acid provides better diffusion of active substances through the skin.

Keywords: anti-aging, l-ascorbic acid, mesotherapy, promoters

Procedia PDF Downloads 263
451 Conserving Naubad Karez Cultural Landscape – a Multi-Criteria Approach to Urban Planning

Authors: Valliyil Govindankutty

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Human civilizations across the globe stand testimony to water being one of the major interaction points with nature. The interactions with nature especially in drier areas revolve around water, be it harnessing, transporting, usage and management. Many ingenious ideas were born, nurtured and developed for harnessing, transporting, storing and distributing water through the areas in the drier parts of the world. Many methods of water extraction, collection and management could be found throughout the world, some of which are associated with efficient, sustained use of surface water, ground water and rain water. Karez is one such ingenious method of collection, transportation, storage and distribution of ground water. Most of the Karez systems in India were developed during reign of Muslim dynasties with ruling class descending from Persia or having influential connections and inviting expert engineers from there. Karez have strongly influenced the village socio-economic organisations due to multitude of uses they were brought into. These are masterpiece engineering structures to collect groundwater and direct it, through a subsurface gallery with a gradual slope, to surface canals that provide water to settlements and agricultural fields. This ingenious technology, karez was result of need for harnessing groundwater in arid areas like that of Bidar. The study views this traditional technology in historical perspective linked to sustainable utilization and management of groundwater and above all the immediate environment. The karez system is one of the best available demonstration of human ingenuity and adaptability to situations and locations of water scarcity. Bidar, capital of erstwhile Bahmani sultanate with a history of more than 700 years or more is one of the heritage cities of present Karnataka State. The unique water systems of Bidar along with other historic entities have been listed under World Heritage Watch List by World Monument Fund. The Historical or cultural landscape in Bidar is very closely associated to the natural resources of the region, Karez systems being one of the best examples. The Karez systems were the lifeline of Bidar’s historical period providing potable water, fulfilling domestic and irrigation needs, both within and outside the fort enclosures. These systems are still functional, but under great pressure and threat of rapid and unplanned urbanisation. The change in land use and fragmentation of land are already paving way for irreversible modification of the karez cultural and geographic landscape. The Paper discusses the significance of character defining elements of Naubad Karez Landscape, highlights the importance of conserving cultural heritage and presents a geographical approach to its revival.

Keywords: Karez, groundwater, traditional water harvesting, cultural heritage landscape, urban planning

Procedia PDF Downloads 490
450 A Principal’s Role in Creating and Sustaining an Inclusive Environment

Authors: Yazmin Pineda Zapata

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Leading a complete school and culture transformation can be a daunting task for any administrator. This is especially true when change agents are advocating for inclusive reform in their schools. As leaders embark on this journey, they must ascertain that an inclusive environment is not a place, a classroom, or a resource setting; it is a place of acceptance nurtured by supportive and meaningful learning opportunities where all students can thrive. A qualitative approach, phenomenology, was used to investigate principals’ actions and behaviors that supported inclusive schooling for students with disabilities. Specifically, this study sought to answer the following research question: How do leaders develop and maintain inclusive education? Fourteen K-12 principals purposefully selected from various sources (e.g., School Wide Integrated Framework for Transformation (SWIFT), The Maryland Coalition for Inclusive Education (MCIE), The Arc of Texas Inclusion Works organization, The Association for Persons with Severe Handicaps (TASH), the CAL State Summer Institute in San Marcos, and the PEAK Parent Center and/or other recognitions were interviewed individually using a semi-structured protocol. Upon completion of data collection, all interviews were transcribed and marked using A priori coding to analyze the responses and establish a correlation among Villa and Thousand’s five organizational supports to achieve inclusive educational reform: Vision, Skills, Incentives, Resources, and Action Plan. The findings of this study reveal the insights of principals who met specific criteria and whose schools had been highlighted as exemplary inclusive schools. Results show that by implementing the five organizational supports, principals were able to develop and sustain successful inclusive environments where both teachers and students were motivated, made capable, and supported through the redefinition and restructuring of systems within the school. Various key details of the five variables for change depict essential components within these systems, which include quality professional development, coaching and modeling of co-teaching strategies, collaborative co-planning, teacher leadership, and continuous stakeholder (e.g., teachers, students, support staff, and parents) involvement. The administrators in this study proved the valuable benefits of inclusive education for students with disabilities and their typically developing peers. Together, along with their teaching and school community, school leaders became capable stakeholders that promoted the vision of inclusion, planned a structured approach, and took action to make it a reality.

Keywords: Inclusive education, leaders, principals, shared-decision making, shared leadership, special education, sustainable change

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449 Person-Centered Approaches in Face-to-Face Interventions to Support Enrolment in Cardiac Rehabilitation: A Scoping Review Study

Authors: Birgit Rasmussen, Thomas Maribo, Bente S. Toft

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BACKGROUND: Cardiac rehabilitation is the standard treatment for ischemic heart disease. Cardiac rehabilitation improves quality of life, reduces mortality and the risk of readmission, and provides patients with valuable knowledge and encouragement from peers and staff. Still, less than half of eligible patients enroll. Face-to-face interventions have the potential to support patients' decision-making and increase enrolment in cardiac rehabilitation. However, we lack knowledge of the content and characteristics of interventions. AIM: The aim was to outline and evaluate the content and characteristics of studies that have reported on face-to-face interventions to encourage enrolment in cardiac rehabilitation in patients with ischemic heart disease. METHOD: This scoping review followed the Joanne Briggs Institute methodology. Based on an a-priori protocol that defined the systematic search criteria, six databases were searched for studies published between 2001 and 2023. Two reviewers independently screened and selected studies. All authors discussed the summarized data prior to the narrative presentation. RESULTS: After screening and full text review of 5583 records, 20 studies of heterogeneous design and content were included. Four studies described the key contents in face-to-face interventions to be education, support of autonomy, addressing reasons for change, and emotional and cognitive support while showing understanding. Two studies used motivational interviewing to target patients' experiences and address worries and anticipated difficulties. Four quantitative studies found associations between enrolment and intention to attend, cardiac rehabilitation barriers, exercise self-efficacy, and perceived control. When patients asked questions, enrolment rates were higher, while providing reassurance and optimism could lead to non-attendance if patients had a high degree of worry. In qualitative studies, support to overcome barriers and knowledge about health benefits from participation in cardiac rehabilitation facilitated enrolment. Feeling reassured that the cardiac condition was good could lead to non-attendance. DISCUSSION AND CONCLUSION: To support patients' enrolment in cardiac rehabilitation, it is recommended that interventions integrate a person-centered dialogue. Individual worries and barriers to cardiac rehabilitation should be jointly explored. When talking with patients for whom worries predominate, the recommendation is to focus on the patients' perspectives and avoid too much focus on reassurance and problem-solving. The patients' perspectives, the mechanisms of change, and the process evaluation of the intervention including person-centeredness are relevant to include in future studies.

Keywords: ischemic heart disease, cardiac rehabilitation, enrolment, person-centered, in-hospital interventions

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448 Theoretical-Methodological Model to Study Vulnerability of Death in the Past from a Bioarchaeological Approach

Authors: Geraldine G. Granados Vazquez

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Every human being is exposed to the risk of dying; wherein some of them are more susceptible than others depending on the cause. Therefore, the cause could be the hazard to die that a group or individual has, making this irreversible damage the condition of vulnerability. Risk is a dynamic concept; which means that it depends on the environmental, social, economic and political conditions. Thus vulnerability may only be evaluated in terms of relative parameters. This research is focusing specifically on building a model that evaluate the risk or propensity of death in past urban societies in connection with the everyday life of individuals, considering that death can be a consequence of two coexisting issues: hazard and the deterioration of the resistance to destruction. One of the most important discussions in bioarchaeology refers to health and life conditions in ancient groups; the researchers are looking for more flexible models that evaluate these topics. In that way, this research proposes a theoretical-methodological model that assess the vulnerability of death in past urban groups. This model pretends to be useful to evaluate the risk of death, considering their sociohistorical context, and their intrinsic biological features. This theoretical and methodological model, propose four areas to assess vulnerability. The first three areas use statistical methods or quantitative analysis. While the last and fourth area, which corresponds to the embodiment, is based on qualitative analysis. The four areas and their techniques proposed are a) Demographic dynamics. From the distribution of age at the time of death, the analysis of mortality will be performed using life tables. From here, four aspects may be inferred: population structure, fertility, mortality-survival, and productivity-migration, b) Frailty. Selective mortality and heterogeneity in frailty can be assessed through the relationship between characteristics and the age at death. There are two indicators used in contemporary populations to evaluate stress: height and linear enamel hypoplasias. Height estimates may account for the individual’s nutrition and health history in specific groups; while enamel hypoplasias are an account of the individual’s first years of life, c) Inequality. Space reflects various sectors of society, also in ancient cities. In general terms, the spatial analysis uses measures of association to show the relationship between frail variables and space, d) Embodiment. The story of everyone leaves some evidence on the body, even in the bones. That led us to think about the dynamic individual's relations in terms of time and space; consequently, the micro analysis of persons will assess vulnerability from the everyday life, where the symbolic meaning also plays a major role. In sum, using some Mesoamerica examples, as study cases, this research demonstrates that not only the intrinsic characteristics related to the age and sex of individuals are conducive to vulnerability, but also the social and historical context that determines their state of frailty before death. An attenuating factor for past groups is that some basic aspects –such as the role they played in everyday life– escape our comprehension, and are still under discussion.

Keywords: bioarchaeology, frailty, Mesoamerica, vulnerability

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447 Protective Effect of Cinnamomum zeylanicum Bark Extract against Doxorubicin Induced Cardiotoxicity: A Preliminary Study

Authors: J. A. N. Sandamali, R. P. Hewawasam, K. A. P. W. Jayatilaka, L. K. B. Mudduwa

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Introduction: Doxorubicin is widely used in the treatment of solid organ tumors and hematological malignancies, but the dose-dependent cardiotoxicity due to free radical formation compromises its clinical utility. Therapeutic strategies which enhance cellular endogenous defense systems have been identified as promising approaches to combat oxidative stress-associated conditions. Cinnamomum zeylanicum (Ceylon cinnamon) has a number antioxidant compounds, which can effectively scavenge reactive oxygen including superoxide anions, hydroxyl radicals and as well as other free radicals. Therefore, the objective of the study was to elucidate the most effective dose of Cinnamomum bark extract which ameliorates doxorubicin-induced cardiotoxicity. Materials and methods: Wistar rats were divided into seven groups of 10 animals in each. Group 1: normal control (distilled water, orally, for 14 days, 10 mL/kg saline, ip, after 16 hours fast on the 11th day); Group 2: doxorubicin control (distilled water, orally, for 14 days, 18 mg/kg doxorubicin, ip, after 16 hour fast on the 11th day); Groups 3-7: five doses of freeze dried aqueous bark extracts (0.125, 0.25, 0.5, 1.0, 2.0g/kg, orally, daily for 14 days, 18 mg/kg doxorubicin, ip, after 16 hours fast on the 11th day). Animals were sacrificed on the 15th day and blood was collected for the estimation of cardiac troponin I (cTnI), AST and LDH concentrations and myocardial tissues were collected for histopathological assessment of myocardial damage and irreversible changes were graded by developing a score. Results: cTnI concentration of groups 1-7 were 0, 161.9, 128.6, 95.9, 38, 19.41 & 12.36 pg/mL showing significant differences (p<0.05) between group 2 and groups 4-7. In groups 1-7, serum AST concentration were 26.82, 68.1, 37.18, 36.23, 26.8, 26.62 & 22.43U/L and LDH concentrations were 1166.13, 2428.84, 1658.35, 1474.34, 1277.58, 1110.21 & 974.40U/L and a significant difference (p<0.05) was observed between group 2 and groups 3-7. The maximum score for myocardial necrosis was observed in group 2. Parallel to the increase of the dosage of plant extract, a gradual reduction of the score for myocardial necrosis was observed in groups 3-7. Reversible histological changes such as vacuolation, congestion were observed in group 2 and all plant treated groups. Haemorrhages, inflammatory cell infiltrations, and interstitial oedema were observed in group 2, but absent in groups treated with higher doses of the plant extract. Discussion & Conclusion: According to the in vitro antioxidant assays performed, Cinnamomum zeylanicum (Ceylon cinnamon) bark possesses high amounts of polyphenolic substances and high antioxidant activity. The present study showed that Cinnamomum zeylanicum extract at 2.0 g/kg possesses the most significant cardioprotective effect against doxorubicin-induced cardiotoxicity. It can be postulated that pretreatment with Cinnamomum bark extract may replenish the cardiomyocytes with antioxidants that are needed for the defense against oxidative stress induced by doxorubicin.

Keywords: cardioprotection, Cinnamomum zeylanicum, doxorubicin, free radicals

Procedia PDF Downloads 158
446 Incidence and Risk Factors of Traumatic Lumbar Puncture in Newborns in a Tertiary Care Hospital

Authors: Heena Dabas, Anju Paul, Suman Chaurasia, Ramesh Agarwal, M. Jeeva Sankar, Anurag Bajpai, Manju Saksena

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Background: Traumatic lumbar puncture (LP) is a common occurrence and causes substantial diagnostic ambiguity. There is paucity of data regarding its epidemiology. Objective: To assess the incidence and risk factors of traumatic LP in newborns. Design/Methods: In a prospective cohort study, all inborn neonates admitted in NICU and planned to undergo LP for a clinical indication of sepsis were included. Neonates with diagnosed intraventricular hemorrhage (IVH) of grade III and IV were excluded. The LP was done by operator - often a fellow or resident assisted by bedside nurse. The unit has policy of not routinely using any sedation/analgesia during the procedure. LP is done by 26 G and 0.5-inch-long hypodermic needle inserted in third or fourth lumbar space while the infant is in lateral position. The infants were monitored clinically and by continuous measurement of vital parameters using multipara monitor during the procedure. The occurrence of traumatic tap along with CSF parameters and other operator and assistant characteristics were recorded at the time of procedure. Traumatic tap was defined as presence of visible blood or more than 500 red blood cells on microscopic examination. Microscopic trauma was defined when CSF is not having visible blood but numerous RBCs. The institutional ethics committee approved the study protocol. A written informed consent from the parents and the health care providers involved was obtained. Neonates were followed up till discharge/death and final diagnosis was assigned along with treating team. Results: A total of 362 (21%) neonates out of 1726 born at the hospital were admitted during the study period (July 2016 to January, 2017). Among these neonates, 97 (26.7%) were suspected of sepsis. A total of 54 neonates were enrolled who met the eligibility criteria and parents consented to participate in the study. The mean (SD) birthweight was 1536 (732) grams and gestational age 32.0 (4.0) weeks. All LPs were indicated for late onset sepsis at the median (IQR) age of 12 (5-39) days. The traumatic LP occurred in 19 neonates (35.1%; 95% C.I 22.6% to 49.3%). Frank blood was observed in 7 (36.8%) and in the remaining, 12(63.1%) CSF was detected to have microscopic trauma. The preliminary risk factor analysis including birth weight, gestational age and operator/assistant and other characteristics did not demonstrate clinically relevant predictors. Conclusion: A significant number of neonates requiring lumbar puncture in our study had high incidence of traumatic tap. We were not able to identify modifiable risk factors. There is a need to understand the reasons and further reduce this issue for improving management in NICUs.

Keywords: incidence, newborn, traumatic, lumbar puncture

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445 Choosing Mountains Over the Beach: Evaluating the Effect of Altitude on Covid Brain Severity and Treatment

Authors: Kennedy Zinn, Chris Anderson

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Chronic Covid syndrome (CCS) is a condition in which individuals who test positive for Covid-19 experience persistent symptoms after recovering from the virus. CCS affects every organ system, including the central nervous system. Neurological “long-haul” symptoms last from a few weeks to several months and include brain fog, chronic fatigue, dyspnea, mood dysregulation, and headaches. Data suggest that 10-30% of individuals testing positive for Covid-19 develop CCS. Current literature indicates a decreased quality of life in persistent symptoms. CCS is a pervasive and pernicious COVID-19 sequelae. More research is needed to understand risk factors, impact, and possible interventions. Research frequently cites cytokine storming as noteworthy etiology in CCS. Cytokine storming is a malfunctional immune response and facilitates multidimensional interconnected physiological responses. The most prominent responses include abnormal blood flow, hypoxia/hypoxemia, inflammation, and endothelial damage. Neurological impairments and pathogenesis in CCS parallel that of traumatic brain injury (TBI). Both exhibit impairments in memory, cognition, mood, sustained attention, and chronic fatigue. Evidence suggests abnormal blood flow, inflammation, and hypoxemia as shared causal factors. Cytokine storming is also typical in mTBI. The shared characteristics in symptoms and etiology suggest potential parallel routes of investigation that allow for better understanding of CCS. Research on the effect of altitude in mTBI varies. Literature finds decreased rates of concussions at higher altitudes. Other studies suggest that at a higher altitude, pre-existing mTBI symptoms are exacerbated. This may mean that in CCS, the geographical location where individuals live and the location where individuals experienced acute Covid-19 symptoms may influence the severity and risk of developing CCS. It also suggests that clinics which treat mTBI patients could also provide benefits for those with CCS. This study aims to examine the relationships between altitude and CCS as a risk factor and investigate the longevity and severity of symptoms in different altitudes. Existing patient data from a concussion clinic using fMRI scans and self-reported symptoms will be used for approximately 30 individuals with CCS symptoms. The association between acclimated altitude and CCS severity will be analyzed. Patients will be classified into low, medium, and high altitude groups and compared for differences on fMRI severity scores and self-reported measures. It is anticipated that individuals living in lower altitudes are at higher risk of developing more severe neuropsychological symptoms in CCS. It is also anticipated that a treatment approach for mTBI will also be beneficial to those with CCS.

Keywords: altitude, chronic covid syndrome, concussion, covid brain, EPIC treatment, fMRI, traumatic brain injury

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444 Artificial Intelligence Models for Detecting Spatiotemporal Crop Water Stress in Automating Irrigation Scheduling: A Review

Authors: Elham Koohi, Silvio Jose Gumiere, Hossein Bonakdari, Saeid Homayouni

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Water used in agricultural crops can be managed by irrigation scheduling based on soil moisture levels and plant water stress thresholds. Automated irrigation scheduling limits crop physiological damage and yield reduction. Knowledge of crop water stress monitoring approaches can be effective in optimizing the use of agricultural water. Understanding the physiological mechanisms of crop responding and adapting to water deficit ensures sustainable agricultural management and food supply. This aim could be achieved by analyzing and diagnosing crop characteristics and their interlinkage with the surrounding environment. Assessments of plant functional types (e.g., leaf area and structure, tree height, rate of evapotranspiration, rate of photosynthesis), controlling changes, and irrigated areas mapping. Calculating thresholds of soil water content parameters, crop water use efficiency, and Nitrogen status make irrigation scheduling decisions more accurate by preventing water limitations between irrigations. Combining Remote Sensing (RS), the Internet of Things (IoT), Artificial Intelligence (AI), and Machine Learning Algorithms (MLAs) can improve measurement accuracies and automate irrigation scheduling. This paper is a review structured by surveying about 100 recent research studies to analyze varied approaches in terms of providing high spatial and temporal resolution mapping, sensor-based Variable Rate Application (VRA) mapping, the relation between spectral and thermal reflectance and different features of crop and soil. The other objective is to assess RS indices formed by choosing specific reflectance bands and identifying the correct spectral band to optimize classification techniques and analyze Proximal Optical Sensors (POSs) to control changes. The innovation of this paper can be defined as categorizing evaluation methodologies of precision irrigation (applying the right practice, at the right place, at the right time, with the right quantity) controlled by soil moisture levels and sensitiveness of crops to water stress, into pre-processing, processing (retrieval algorithms), and post-processing parts. Then, the main idea of this research is to analyze the error reasons and/or values in employing different approaches in three proposed parts reported by recent studies. Additionally, as an overview conclusion tried to decompose different approaches to optimizing indices, calibration methods for the sensors, thresholding and prediction models prone to errors, and improvements in classification accuracy for mapping changes.

Keywords: agricultural crops, crop water stress detection, irrigation scheduling, precision agriculture, remote sensing

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443 The Structural Alteration of DNA Native Structure of Staphylococcus aureus Bacteria by Designed Quinoxaline Small Molecules Result in Their Antibacterial Properties

Authors: Jeet Chakraborty, Sanjay Dutta

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Antibiotic resistance by bacteria has proved to be a severe threat to mankind in recent times, and this fortifies an urgency to design and develop potent antibacterial small molecules/compounds with nonconventional mechanisms than the conventional ones. DNA carries the genetic signature of any organism, and bacteria maintain their genomic DNA inside the cell in a well-regulated compact form with the help of various nucleoid associated proteins like HU, HNS, etc. These proteins control various fundamental processes like gene expression, replication, etc., inside the cell. Alteration of the native DNA structure of bacteria can lead to severe consequences in cellular processes inside the bacterial cell that ultimately result in the death of the organism. The change in the global DNA structure by small molecules initiates a plethora of cellular responses that have not been very well investigated. Echinomycin and Triostin-A are biologically active Quinoxaline small molecules that typically consist of a quinoxaline chromophore attached with an octadepsipeptide ring. They bind to double-stranded DNA in a sequence-specific way and have high activity against a wide variety of bacteria, mainly against Gram-positive ones. To date, few synthetic quinoxaline scaffolds were synthesized, displaying antibacterial potential against a broad scale of pathogenic bacteria. QNOs (Quinoxaline N-oxides) are known to target DNA and instigate reactive oxygen species (ROS) production in bacteria, thereby exhibiting antibacterial properties. The divergent role of Quinoxaline small molecules in medicinal research qualifies them for the evaluation of their antimicrobial properties as a potential candidate. The previous study from our lab has given new insights on a 6-nitroquinoxaline derivative 1d as an intercalator of DNA, which induces conformational changes in DNA upon binding.7 The binding event observed was dependent on the presence of a crucial benzyl substituent on the quinoxaline moiety. This was associated with a large induced CD (ICD) appearing in a sigmoidal pattern upon the interaction of 1d with dsDNA. The induction of DNA superstructures by 1d at high Drug:DNA ratios was observed that ultimately led to DNA condensation. Eviction of invitro-assembled nucleosome upon treatment with a high dose of 1d was also observed. In this work, monoquinoxaline derivatives of 1d were synthesized by various modifications of the 1d scaffold. The set of synthesized 6-nitroquinoxaline derivatives along with 1d were all subjected to antibacterial evaluation across five different bacteria species. Among the compound set, 3a displayed potent antibacterial activity against Staphylococcus aureus bacteria. 3a was further subjected to various biophysical studies to check whether the DNA structural alteration potential was still intact. The biological response of S. aureus cells upon treatment with 3a was studied using various cell biology processes, which led to the conclusion that 3d can initiate DNA damage in the S. aureus cells. Finally, the potential of 3a in disrupting preformed S.aureus and S.epidermidis biofilms was also studied.

Keywords: DNA structural change, antibacterial, intercalator, DNA superstructures, biofilms

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442 Monitoring Air Pollution Effects on Children for Supporting Public Health Policy: Preliminary Results of MAPEC_LIFE Project

Authors: Elisabetta Ceretti, Silvia Bonizzoni, Alberto Bonetti, Milena Villarini, Marco Verani, Maria Antonella De Donno, Sara Bonetta, Umberto Gelatti

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Introduction: Air pollution is a global problem. In 2013, the International Agency for Research on Cancer (IARC) classified air pollution and particulate matter as carcinogenic to human. The study of the health effects of air pollution in children is very important because they are a high-risk group in terms of the health effects of air pollution and early exposure during childhood can increase the risk of developing chronic diseases in adulthood. The MAPEC_LIFE (Monitoring Air Pollution Effects on Children for supporting public health policy) is a project founded by EU Life+ Programme which intends to evaluate the associations between air pollution and early biological effects in children and to propose a model for estimating the global risk of early biological effects due to air pollutants and other factors in children. Methods: The study was carried out on 6-8-year-old children living in five Italian towns in two different seasons. Two biomarkers of early biological effects, primary DNA damage detected with the comet assay and frequency of micronuclei, were investigated in buccal cells of children. Details of children diseases, socio-economic status, exposures to other pollutants and life-style were collected using a questionnaire administered to children’s parents. Child exposure to urban air pollution was assessed by analysing PM0.5 samples collected in the school areas for PAHs and nitro-PAHs concentration, lung toxicity and in vitro genotoxicity on bacterial and human cells. Data on the chemical features of the urban air during the study period were obtained from the Regional Agency for Environmental Protection. The project created also the opportunity to approach the issue of air pollution with the children, trying to raise their awareness on air quality, its health effects and some healthy behaviors by means of an educational intervention in the schools. Results: 1315 children were recruited for the study and participate in the first sampling campaign in the five towns. The second campaign, on the same children, is still ongoing. The preliminary results of the tests on buccal mucosa cells of children will be presented during the conference as well as the preliminary data about the chemical composition and the toxicity and genotoxicity features of PM0.5 samples. The educational package was tested on 250 children of the primary school and showed to be very useful, improving children knowledge about air pollution and its effects and stimulating their interest. Conclusions: The associations between levels of air pollutants, air mutagenicity and biomarkers of early effects will be investigated. A tentative model to calculate the global absolute risk of having early biological effects for air pollution and other variables together will be proposed and may be useful to support policy-making and community interventions to protect children from possible health effects of air pollutants.

Keywords: air pollution exposure, biomarkers of early effects, children, public health policy

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441 Antibacterial Effects of Zinc Oxide Nanoparticles as Alternative Therapy on Drug-Resistant Group B Streptococcus Strains Isolated from Pregnant Women

Authors: Leila Fozouni, Anahita Mazandarani

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Background: Maternal infections are the most common cause of infections in infants, and the level of infection and its severity highly depends on the degree of colonization of the bacteria in the mother; so, the occurrence of aggressive diseases is not unpredictable in mothers with very high colonization. Group B Streptococcus is part of the normal flora of the gastrointestinal and genital tracts in women and is the leading cause of septicemia and meningitis in newborns. Today Zinc oxide nanoparticle is regarded as one of the most commonly used and safest nanoparticles for defeating Gram-positive and Gram-negative bacteria. This study aims to determine the antibacterial effects of Zinc oxide on the growth of drug-resistant group B Streptococcus strains isolated from pregnant women. Materials and Methods: This cross-sectional study was conducted on 150 pregnant women of 28–37 weeks admitted to seven hospitals and maternity wards in Golestan province, northeast of Iran. For bacterial identification, rectovaginal swabs were firstly inoculated to the Todd-Hewitt Broth and cultured in blood agar (containing 5% sheep blood). Then microbiologic and PCR methods were performed to detect group B Streptococci. Disk diffusion and broth microdilution tests were used to determine the bacterial susceptibility to antibiotics according to CLSI M100(2021) criteria. The antibacterial properties of Zinc oxide nanoparticles were evaluated using the agar well-diffusion method. Results: The prevalence of group B Streptococcus was 18% in pregnant women. Out of twenty-seven positive cultures, 62.96% were higher than thirty years old. Ninety percent and 45% of isolates were resistant to clindamycin and erythromycin, respectively, and susceptibility to cefazolin was 71%. In addition, susceptibility to ampicillin and penicillin were 74% and 55%, respectively. The results showed that 82% of erythromycin-resistant, 92% clindamycin-resistant, and 78% of cefazolin-resistant isolates were eliminated by zinc oxide nanoparticles at a concentration of 100 mg/L of the nanoparticle. Furthermore, ZnONPs could inhibit all drug-resistant isolates at a concentration of 200 mg/mL (MIC90 ≥ 200). Conclusion: Since the drug resistance of group B streptococci against various antibiotics is increasing, determining and investigating the drug-resistance pattern of this bacterium to different antibiotics in order to prevent arbitrary consumption of antibiotics by pregnant women and ultimately prevent Infant mortality seems necessary. Generally, ZnONPs showed a high antimicrobial effect, and it was revealed that the bactericide effect increases upon the increase in the concentration of the nanoparticle.

Keywords: group B beta-hemolytic streptococcus, pregnant women, zinc oxide nanoparticles, drug resistance

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440 Enhancement of Radiosensitization by Aptamer 5TR1-Functionalized AgNCs for Triple-Negative Breast Cancer

Authors: Xuechun Kan, Dongdong Li, Fan Li, Peidang Liu

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Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer with a poor prognosis, and radiotherapy is one of the main treatment methods. However, due to the obvious resistance of tumor cells to radiotherapy, high dose of ionizing radiation is required during radiotherapy, which causes serious damage to normal tissues near the tumor. Therefore, how to improve radiotherapy resistance and enhance the specific killing of tumor cells by radiation is a hot issue that needs to be solved in clinic. Recent studies have shown that silver-based nanoparticles have strong radiosensitization, and silver nanoclusters (AgNCs) also provide a broad prospect for tumor targeted radiosensitization therapy due to their ultra-small size, low toxicity or non-toxicity, self-fluorescence and strong photostability. Aptamer 5TR1 is a 25-base oligonucleotide aptamer that can specifically bind to mucin-1 highly expressed on the membrane surface of TNBC 4T1 cells, and can be used as a highly efficient tumor targeting molecule. In this study, AgNCs were synthesized by DNA template based on 5TR1 aptamer (NC-T5-5TR1), and its role as a targeted radiosensitizer in TNBC radiotherapy was investigated. The optimal DNA template was first screened by fluorescence emission spectroscopy, and NC-T5-5TR1 was prepared. NC-T5-5TR1 was characterized by transmission electron microscopy, ultraviolet-visible spectroscopy and dynamic light scattering. The inhibitory effect of NC-T5-5TR1 on cell activity was evaluated using the MTT method. Laser confocal microscopy was employed to observe NC-T5-5TR1 targeting 4T1 cells and verify its self-fluorescence characteristics. The uptake of NC-T5-5TR1 by 4T1 cells was observed by dark-field imaging, and the uptake peak was evaluated by inductively coupled plasma mass spectrometry. The radiation sensitization effect of NC-T5-5TR1 was evaluated through cell cloning and in vivo anti-tumor experiments. Annexin V-FITC/PI double staining flow cytometry was utilized to detect the impact of nanomaterials combined with radiotherapy on apoptosis. The results demonstrated that the particle size of NC-T5-5TR1 is about 2 nm, and the UV-visible absorption spectrum detection verifies the successful construction of NC-T5-5TR1, and it shows good dispersion. NC-T5-5TR1 significantly inhibited the activity of 4T1 cells and effectively targeted and fluoresced within 4T1 cells. The uptake of NC-T5-5TR1 reached its peak at 3 h in the tumor area. Compared with AgNCs without aptamer modification, NC-T5-5TR1 exhibited superior radiation sensitization, and combined radiotherapy significantly inhibited the activity of 4T1 cells and tumor growth in 4T1-bearing mice. The apoptosis level of NC-T5-5TR1 combined with radiation was significantly increased. These findings provide important theoretical and experimental support for NC-T5-5TR1 as a radiation sensitizer for TNBC.

Keywords: 5TR1 aptamer, silver nanoclusters, radio sensitization, triple-negative breast cancer

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