Search results for: local coronary artery disease

Authors: Stephanie Wall, Guido Wimmers

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The construction and operation of buildings greatly contribute to environmental degradation through resource and energy consumption and greenhouse gas emissions. The design of the envelope system affects the environmental impact of a building in two major ways; 1) high thermal performance and air tightness can significantly reduce the operational energy of the building and 2) the material selection for the envelope largely impacts the embodied energy of the building. Life cycle assessment (LCA) is a scientific methodology that is used to systematically analyze the environmental load of processes or products, such as buildings, over their life. The paper will discuss the results of a comparative LCA of different envelope designs and the long-term monitoring of the Wood Innovation Research Lab (WIRL); a Passive House (PH), industrial building under construction in Prince George, Canada. The WIRL has a footprint of 30m x 30m on a concrete raft slab foundation and consists of shop space as well as a portion of the building that includes a two-story office/classroom space. The lab building goes beyond what was previously thought possible in regards to energy efficiency of industrial buildings in cold climates due to their large volume to surface ratio, small floor area, and high air change rate, and will be the first PH certified industrial building in Canada. These challenges were mitigated through the envelope design which utilizes solar gains while minimizing overheating, reduces thermal bridges with thick (570mm) prefabricated truss walls filled with blown in mineral wool insulation and a concrete slab and roof insulated with EPS rigid insulation. The envelope design results in lower operational and embodied energy when compared to buildings built to local codes or with steel. The LCA conducted using Athena Impact Estimator for Buildings identifies project specific hot spots as well illustrates that for high-efficiency buildings where the operational energy is relatively low; the embodied energy of the material selection becomes a significant design decision as it greatly impacts the overall environmental footprint of the building. The results of the LCA will be reinforced by long-term monitoring of the buildings envelope performance through the installation of temperature and humidity sensors throughout the floor slab, wall and roof panels and through detailed metering of the energy consumption. The data collected from the sensors will also be used to reinforce the results of hygrothermal analysis using WUFI®, a program used to verify the durability of the wall and roof panels. The WIRL provides an opportunity to showcase the use of wood in a high performance envelope of an industrial building and to emphasize the importance of considering the embodied energy of a material in the early stages of design. The results of the LCA will be of interest to leading researchers and scientists committed to finding sustainable solutions for new construction and high-performance buildings.

Keywords: high performance envelope, life cycle assessment, long term monitoring, passive house, prefabricated panels

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Authors: Catherine Constantinidis (Nee Tsacalos)

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This paper presents one aspect of the larger Masters qualitative study exploring the roles of married Greek Orthodox clergy, the Priest and Presbytera, under the wing of the Greek Orthodox Archdiocese of Australia. This ground breaking research necessitated the creation of primary data within a phenomenological paradigm drawing from lived experiences of the Priests and Presbyteres in contemporary society. As a Social Worker, a bilingual (Greek/English) Mental Health practitioner and a Presbytera, the questions constantly raised and pondered are: Who do the Priest and Presbytera turn to when they experience difficulties or problems? Where do they go for support? What is in place for their emotional and psychological health and well-being? Who cares for the spiritual carer? Who is there to catch our falling clergy and their wives? What is their 'safety net'? Identified phenomena of angst, stress, frustration and confusion experienced by the Priest and (by extension) the Presbytera, within their position, coupled with basic assumptions, perceptions and expectations about their roles, the role of the organisation (the Church), and their role as spouse often caused confusion and in some cases conflict. Unpacking this complex and multi-dimensional relationship highlighted not only the roller coaster of emotions, potentially affecting their physical and mental health, but also the impact on the interwoven relationships of marriage and ministry. The author considers these phenomena in the light of bilingual cultural and religious organisational practice frameworks, specifically the Greek Orthodox Church, whilst filtering these findings through a mental health lens. One could argue that it is an expectation that clergy (and by default their wives) take on the responsibility to be kind, nurturing and supportive to others. However, when it comes to taking care of self, they are not nearly as kind. This research looks at a recurrent theme throughout the interviews where all participants talked about limited support systems and poor self care strategies and the impact this has on their ministry, mental, emotional, and physical health and ultimately on their relationships with self and others. The struggle all participants encountered at some point in their ministry was physical, spiritual and psychological burn out. The overall aim of the researcher is to provide a voice for the Priest and the Presbytera painting a clearer picture of these roles and facilitating an awareness of struggles and dilemmas faced in their ministry. It is hoped these identified gaps in self care strategies and support systems will provide solid foundations for building a culturally sensitive, empathetic and effective support system framework, incorporating the spiritual and psychological well-being of the Priest and Presbytera, a ‘safety net’. A supplementary aim is to inform and guide ministry practice frameworks for clergy, spouses, the church hierarchy and religious organisations on a local and global platform incorporating some sort of self-care system.

Keywords: care for the carer, mental health, Priest, Presbytera, religion, support system

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Authors: Patrícia Pires, Renata Vaz, Bárbara Teles, Marco Pato, Pedro Beckert

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Introduction: The management of lateral third clavicle fractures can be challenging due to difficulty in distinguishing subtle variations in the fracture pattern, which may be suggestive of potential fracture instability. They occur most often in men between 30 and 50 years of age, and in individuals over 70 years of age, its distribution is equal between both men and women. These fractures account for 10%–30% of all clavicle fractures and roughly 30%–45% of all clavicle nonunion fractures. Lateral third clavicle fractures may be treated conservatively or surgically, and there is no gold standard, although the risk of nonunion or pseudoarthrosis impacts the recommendation of surgical treatment when these fractures are unstable. There are many strategies for surgical treatment, including locking plates, hook plates fixation, coracoclavicular fixation using suture anchors, devices or screws, tension band fixation with suture or wire, transacromial Kirschner wire fixation and arthroscopically assisted techniques. Whenever taking the hardware into consideration, we must not disregard that obtaining adequate lateral fixation of small fragments is a difficult task, and plates are more associated to local irritation. The aim of the appropriate treatment is to ensure fracture healing and a rapid return to preinjury activities of daily living but, as explained, definitive treatment strategies have not been established and the variety of techniques avalilable add up to the discussion of this topic. Methods and Results: We present a clinical case of a 43-year-old man with the diagnosis of a lateral third clavicle fracture (Neer IIC) in the sequence of a fall on his right shoulder after a bicycle fall. He was operated three days after the injury, and through K-wire temporary fixation and indirect reduction using a ZipTight, he underwent osteosynthesis with an interfragmentary figure-of-eight tension band with polydioxanone suture (PDS). Two weeks later, there was a good aligment. He kept the sling until 6 weeks pos-op, avoiding efforts. At 7-weeks pos-op, there was still a good aligment, starting the physiotherapy exercises. After 10 months, he had no limitation in mobility or pain and returned to work with complete recovery in strength. Conclusion: Some distal clavicle fractures may be conservatively treated, but it is widely accepted that unstable fractures require surgical treatment to obtain superior clinical outcomes. In the clinical case presented, the authors chose an osteosuture technique due to the fracture pattern, its location. Since there isn´t a consensus on the prefered fixation method, it is important for surgeons to be skilled in various techniques and decide with their patient which approach is most appropriate for them, weighting the risk-benefit of each method. For instance, with the suture technique used, there is no wire migration or breakage, and it doesn´t require a reoperation for hardware removal; there is also less tissue exposure since it requires a smaller approach in comparison to the plate fixation and avoids cuff tears like the hook plate. The good clinical outcome on this case report serves the purpose of expanding the consideration of this method has a therapeutic option.

Keywords: lateral third, clavicle, suture, fixation

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Authors: G. A. Asciak, C. Camilleri, A. Rizzo

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The waste management in Malta is a national challenge. Coupled with Malta’s recent economic boom, which has seen massive growth in several sectors, especially the construction industry, drastic actions need to be taken. Wood waste, currently being dumped in landfills, is one type of waste which has increased astronomically. This research study aims to carry out a thorough examination on the possibility of using this waste as a biomass resource and adopting a waste-to-energy technology in order to generate electrical energy. This study is composed of three distinct yet interdependent phases, namely, data collection from the local SMEs, thermal analysis using the bomb calorimeter, and generation of energy from wood waste using a micro biomass plant. Data collection from SMEs specializing in wood works was carried out to obtain information regarding the available types of wood waste, the annual weight of imported wood, and to analyse the manner in which wood shavings are used after wood is manufactured. From this analysis, it resulted that five most common types of wood available in Malta which would suitable for generating energy are Oak (hardwood), Beech (hardwood), Red Beech (softwood), African Walnut (softwood) and Iroko (hardwood). Subsequently, based on the information collected, a thermal analysis using a 6200 Isoperibol calorimeter on the five most common types of wood was performed. This analysis was done so as to give a clear indication with regards to the burning potential, which will be valuable when testing the wood in the biomass plant. The experiments carried out in this phase provided a clear indication that the African Walnut generated the highest gross calorific value. This means that this type of wood released the highest amount of heat during the combustion in the calorimeter. This is due to the high presence of extractives and lignin, which accounts for a slightly higher gross calorific value. This is followed by Red Beech and Oak. Moreover, based on the findings of the first phase, both the African Walnut and Red Beech are highly imported in the Maltese Islands for use in various purposes. Oak, which has the third highest gross calorific value is the most imported and common wood used. From the five types of wood, three were chosen for use in the power plant on the basis of their popularity and their heating values. The PP20 biomass plant was used to burn the three types of shavings in order to compare results related to the estimated feedstock consumed by the plant, the high temperatures generated, the time taken by the plant to produce gasification temperatures, and the projected electrical power attributed to each wood type. From the experiments, it emerged that whilst all three types reached the required gasification temperature and thus, are feasible for electrical energy generation. African Walnut was deemed to be the most suitable fast-burning fuel. This is followed by Red-beech and Oak, which required a longer period of time to reach the required gasification temperatures. The results obtained provide a clear indication that wood waste can not only be treated instead of being dumped in dumped in landfill but coupled.

Keywords: biomass, isoperibol calorimeter, waste-to-energy technology, wood

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Authors: Jitka Rychtarikova

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Regional differences in mortality in the Czech Republic (CR) may be moderate from a broader European perspective, but important discrepancies in life expectancy can be found between smaller territorial units. In this study territorial units are based on Administrative Districts of Municipalities with Extended Powers (MEP). This definition came into force January 1, 2003. There are 205 units and the city of Prague. MEP represents the smallest unit for which mortality patterns based on life tables can be investigated and the Czech Statistical Office has been calculating such life tables (every five-years) since 2004. MEP life tables from 2009-2013 for males and females allowed the investigation of three main life cycles with the use of temporary life expectancies between the exact ages of 0 and 35; 35 and 65; and the life expectancy at exact age 65. The results showed regional survival inequalities primarily in adult and older ages. Consequently, only mortality indicators for adult and elderly population were related to census 2011 unlinked data for the same age groups. The most relevant socio-economic factors taken from the census are: having a partner, educational level and unemployment rate. The unemployment rate was measured for adults aged 35-64 completed years. Exploratory spatial data analysis methods were used to detect regional patterns in spatially contiguous units of MEP. The presence of spatial non-stationarity (spatial autocorrelation) of mortality levels for male and female adults (35-64), and elderly males and females (65+) was tested using global Moran’s I. Spatial autocorrelation of mortality patterns was mapped using local Moran’s I with the intention to depict clusters of low or high mortality and spatial outliers for two age groups (35-64 and 65+). The highest Moran’s I was observed for male temporary life expectancy between exact ages 35 and 65 (0.52) and the lowest was among women with life expectancy of 65 (0.26). Generally, men showed stronger spatial autocorrelation compared to women. The relationship between mortality indicators such as life expectancies and socio-economic factors like the percentage of males/females having a partner; percentage of males/females with at least higher secondary education; and percentage of unemployed males/females from economically active population aged 35-64 years, was evaluated using multiple regression (OLS). The results were then compared to outputs from geographically weighted regression (GWR). In the Czech Republic, there are two broader territories North-West Bohemia (NWB) and North Moravia (NM), in which excess mortality is well established. Results of the t-test of spatial regression showed that for males aged 30-64 the association between mortality and unemployment (when adjusted for education and partnership) was stronger in NM compared to NWB, while educational level impacted the length of survival more in NWB. Geographic variation and relationships in mortality of the CR MEP will also be tested using the spatial Durbin approach. The calculations were conducted by means of ArcGIS 10.6 and SAS 9.4.

Keywords: Czech Republic, mortality, municipality, socio-economic factors, spatial analysis

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Authors: Mariia A. Parfenenko, Ilya S. Dantsev, Sergei V. Bochenkov, Natalia V. Vinogradova, Olga S. Groznova, Victoria Yu. Voinova

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Introduction: Autism is the most common neurodevelopmental disorder. Autism is characterized by difficulties in social interaction and adherence to stereotypic behavioral patterns and frequently co-occurs with epilepsy, intellectual disabilities, connective tissue disorders, and other conditions. CHD8 codes for chromodomain-helicase-DNA-binding protein 8 - a chromatin remodeler that regulates cellular proliferation and neurodevelopment in embryogenesis. CHD8 is one of the genes most frequently involved in autism. Patients and methods: 2 unrelated male patients, P3 and P12, aged 3 and 12 years old, underwent whole genome sequencing, which determined that they both had different likely pathogenic variants, both previously undescribed in literature. Sanger sequencing later determined that P12 inherited the variant from his affected mother. Results: P3 and P12 presented with autism, a developmental delay, ataxia, sleep disorders, overgrowth, and macrocephaly, as well as other clinical features typically present in patients with causative variants in CHD8. The mother of P12 also has autistic traits, as well as ataxia, hypotonia, sleep disorders, and other symptoms. However, P3 and P12 also have different cardiac abnormalities. P3 had signs of a repolarization disorder: a flattened T wave in the III and aVF derivations and a negative T wave in the V1-V2 derivations. He also had structural valve anomalies with associated regurgitation, local contractility impairment of the left ventricular, and diastolic dysfunction of the right ventricle. Meanwhile, P12 had Wolff-Parkinson-White syndrome and underwent radiofrequency ablation at the age of 2 years. At the time of observation, P12 had mild sinus arrhythmia and an incomplete right bundle branch block, as well as arterial hypertension. Discussion: Cardiac abnormalities were not previously reported in patients with causative variants in CHD8. The underlying mechanism for the formation of those abnormalities is currently unknown. However, the two hypotheses are either a disordered interaction with CHD7 – another chromodomain remodeler known to be directly involved in the cardiophenotype of CHARGE syndrome – a rare condition characterized by coloboma, heart defects and growth abnormalities, or the disrupted functioning of CHD8 as an A-Kinase Anchoring Protein, which are known to modulate cardiac function. Conclusion: We observed 2 unrelated autistic males with likely pathogenic variants in CHD8 that presented with typical symptoms of CHD8-related neurodevelopmental disorder, as well as cardiac abnormalities. Cardiac abnormalities have, until now, been considered uncharacteristic for patients with causative variants in CHD8. Further accumulation of data, including experimental evidence of the involvement of CHD8 in heart formation, will elucidate the mechanism underlying the cardiophenotype of those patients. Acknowledgements: Molecular genetic testing of the patients was made possible by the Charity Fund for medical and social genetic aid projects «Life Genome.»

Keywords: autism spectrum disorders, chromodomain-helicase-DNA-binding protein 8, neurodevelopmental disorder, cardio phenotype

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Authors: Doris C. C. K. Kowaltowski, Marcella S. Deliberador

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The architectural design process, in general, is becoming more complex, as new technical, social, environmental, and economical requirements are imposed. For school buildings, this scenario is also valid. The quality of a school building depends on known design criteria and professional knowledge, as well as feedback from building performance assessments. To attain high-performance school buildings, a design process should add a multidisciplinary team, through an integrated process, to ensure that the various specialists contribute at an early stage to design solutions. The participation of stakeholders is of special importance at the programming phase when the search for the most appropriate design solutions is underway. The composition of a multidisciplinary team should comprise specialists in education, design professionals, and consultants in various fields such as environmental comfort and psychology, sustainability, safety and security, as well as administrators, public officials and neighbourhood representatives. Users, or potential users (teachers, parents, students, school officials, and staff), should be involved. User expectations must be guided, however, toward a proper understanding of a response of design to needs to avoid disappointment. In this context, appropriate tools should be introduced to organize such diverse participants and ensure a rich and focused response to needs and a productive outcome of programming sessions. In this paper, different stakeholder in a school design process are discussed in relation to their specific contributions and a tool in the form of a card game is described to structure the design debates and ensure a comprehensive decision-making process. The game is based on design patterns for school architecture as found in the literature and is adapted to a specific reality: State-run public schools in São Paulo, Brazil. In this State, school buildings are managed by a foundation called Fundação para o Desenvolvimento da Educação (FDE). FDE supervises new designs and is responsible for the maintenance of ~ 5000 schools. The design process of this context was characterised with a recommendation to improve the programming phase. Card games can create a common environment, to which all participants can relate and, therefore, can contribute to briefing debates on an equal footing. The cards of the game described here represent essential school design themes as found in the literature. The tool was tested with stakeholder groups and with architecture students. In both situations, the game proved to be an efficient tool to stimulate school design discussions and to aid in the elaboration of a rich, focused and thoughtful architectural program for a given demand. The game organizes the debates and all participants are shown to spontaneously contribute each in his own field of expertise to the decision-making process. Although the game was specifically based on a local school design process it shows potential for other contexts because the content is based on known facts, needs and concepts of school design, which are global. A structured briefing phase with diverse stakeholder participation can enrich the design process and consequently improve the quality of school buildings.

Keywords: architectural program, design process, school building design, stakeholder

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Authors: Khan Farhan Rafat, Riaz Ahmed

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Renowned offshore organizations are drifting towards collaborative exertion to win and implement international projects for business gains. However, devoid of financial constraints, with the availability of skilled professionals, and despite improved project management practices through state-of-the-art tools and techniques, project delays have become a norm these days. This situation calls for exploring the factor(s) affecting the bonding between project management performance and project success. In the context of the well-known 3M’s of project management (that is, manpower, machinery, and materials), machinery and materials are dependent upon manpower. Because the body of knowledge inveterate on the influence of national culture on men, hence, the realization of the impact on the link between project management performance and project success need to be investigated in detail to arrive at the possible cause(s) of project delays. This research initiative was, therefore, undertaken to fill the research gap. The unit of analysis for the proposed research excretion was the individuals who had worked on skyscraper construction projects. In reverent studies, project management is best described using construction examples. It is due to this reason that the project oriented city of Dubai was chosen to reconnoiter on causes of project delays. A structured questionnaire survey was disseminated online with the courtesy of the Project Management Institute local chapter to carry out the cross-sectional study. The Construction Industry Institute, Austin, of the United States of America along with 23 high-rise builders in Dubai were also contacted by email requesting for their contribution to the study and providing them with the online link to the survey questionnaire. The reliability of the instrument was warranted using Cronbach’s alpha coefficient of 0.70. The appropriateness of sampling adequacy and homogeneity in variance was ensured by keeping Kaiser–Meyer–Olkin (KMO) and Bartlett’s test of sphericity in the range ≥ 0.60 and < 0.05, respectively. Factor analysis was used to verify construct validity. During exploratory factor analysis, all items were loaded using a threshold of 0.4. Four hundred and seventeen respondents, including members from top management, project managers, and project staff, contributed to the study. The link between project management performance and project success was significant at 0.01 level (2-tailed), and 0.05 level (2-tailed) for Pearson’s correlation. Before initiating the moderator analysis test for linearity, multicollinearity, outliers, leverage points and influential cases, test for homoscedasticity and normality were carried out which are prerequisites for conducting moderator review. The moderator analysis, using a macro named PROCESS, was performed to verify the hypothesis that national culture has an influence on the said link. The empirical findings, when compared with Hofstede's results, showed high power distance as the cause of construction project delays in Dubai. The research outcome calls for the project sponsors and top management to reshape their project management strategy and allow for low power distance between management and project personnel for timely completion of projects.

Keywords: causes of construction project delays, construction industry, construction management, power distance

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Authors: Mansoureh Zangiabadi, Shamil Velji, Rajendra Kelkar, Neal Wade, Volker Pickert

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The EU has set itself a long-term goal of reducing greenhouse gas emissions by 80-95% of the 1990 levels by 2050 as set in the Energy Roadmap 2050. This paper reports on the European Union H2020 funded E-Lobster project which demonstrates tools and technologies, software and hardware in integrating the grid distribution, and the railway power systems with power electronics technologies (Smart Soft Open Point - sSOP) and local energy storage. In this context this paper describes the existing policies and regulatory frameworks of the energy market at European level with a special focus then at National level, on the countries where the members of the consortium are located, and where the demonstration activities will be implemented. By taking into account the disciplinary approach of E-Lobster, the main policy areas investigated includes electricity, energy market, energy efficiency, transport and smart cities. Energy storage will play a key role in enabling the EU to develop a low-carbon electricity system. In recent years, Energy Storage System (ESSs) are gaining importance due to emerging applications, especially electrification of the transportation sector and grid integration of volatile renewables. The need for storage systems led to ESS technologies performance improvements and significant price decline. This allows for opening a new market where ESSs can be a reliable and economical solution. One such emerging market for ESS is R+G management which will be investigated and demonstrated within E-Lobster project. The surplus of energy in one type of power system (e.g., due to metro braking) might be directly transferred to the other power system (or vice versa). However, it would usually happen at unfavourable instances when the recipient does not need additional power. Thus, the role of ESS is to enhance advantages coming from interconnection of the railway power systems and distribution grids by offering additional energy buffer. Consequently, the surplus/deficit of energy in, e.g. railway power systems, is not to be immediately transferred to/from the distribution grid but it could be stored and used when it is really needed. This will assure better energy management exchange between the railway power systems and distribution grids and lead to more efficient loss reduction. In this framework, to identify the existing policies and regulatory frameworks is crucial for the project activities and for the future development of business models for the E-Lobster solutions. The projections carried out by the European Commission, the Member States and stakeholders and their analysis indicated some trends, challenges, opportunities and structural changes needed to design the policy measures to provide the appropriate framework for investors. This study will be used as reference for the discussion in the envisaged workshops with stakeholders (DSOs and Transport Managers) in the E-Lobster project.

Keywords: light railway, electrical distribution network, Electrical Energy Storage, policy

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Authors: Anuj Tyagi, Balwinder Singh, Naveen Kumar B. T., Niraj K. Singh

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Characterization of diverse microbial communities in specific environment plays a crucial role in the better understanding of their functional relationship with the ecosystem. It is now well established that gut microbiome of fish is not the simple replication of microbiota of surrounding local habitat, and extensive species, dietary, physiological and metabolic variations in fishes may have a significant impact on its composition. Moreover, overuse of antibiotics in human, veterinary and aquaculture medicine has led to rapid emergence and propagation of antibiotic resistance genes (ARGs) in the aquatic environment. Microbial communities harboring specific ARGs not only get a preferential edge during selective antibiotic exposure but also possess the significant risk of ARGs transfer to other non-resistance bacteria within the confined environments. This phenomenon may lead to the emergence of habitat-specific microbial resistomes and subsequent emergence of virulent antibiotic-resistant pathogens with severe fish and consumer health consequences. In this study, gut microbiota of freshwater carp (Labeo rohita) was investigated by shotgun metagenomics to understand its taxonomic composition and functional capabilities. Metagenomic DNA, extracted from the fish gut, was subjected to sequencing on Illumina NextSeq to generate paired-end (PE) 2 x 150 bp sequencing reads. After the QC of raw sequencing data by Trimmomatic, taxonomic analysis by Kraken2 taxonomic sequence classification system revealed the presence of 36 phyla, 326 families and 985 genera in the fish gut microbiome. At phylum level, Proteobacteria accounted for more than three-fourths of total bacterial populations followed by Actinobacteria (14%) and Cyanobacteria (3%). Commonly used probiotic bacteria (Bacillus, Lactobacillus, Streptococcus, and Lactococcus) were found to be very less prevalent in fish gut. After sequencing data assembly by MEGAHIT v1.1.2 assembler and PROKKA automated analysis pipeline, pathway analysis revealed the presence of 1,608 Metacyc pathways in the fish gut microbiome. Biosynthesis pathways were found to be the most dominant (51%) followed by degradation (39%), energy-metabolism (4%) and fermentation (2%). Almost one-third (33%) of biosynthesis pathways were involved in the synthesis of secondary metabolites. Metabolic pathways for the biosynthesis of 35 antibiotic types were also present, and these accounted for 5% of overall metabolic pathways in the fish gut microbiome. Fifty-one different types of antibiotic resistance genes (ARGs) belonging to 15 antimicrobial resistance (AMR) gene families and conferring resistance against 24 antibiotic types were detected in fish gut. More than 90% ARGs in fish gut microbiome were against beta-lactams (penicillins, cephalosporins, penems, and monobactams). Resistance against tetracycline, macrolides, fluoroquinolones, and phenicols ranged from 0.7% to 1.3%. Some of the ARGs for multi-drug resistance were also found to be located on sequences of plasmid origin. The presence of pathogenic bacteria and ARGs on plasmid sequences suggested the potential risk due to horizontal gene transfer in the confined gut environment.

Keywords: antibiotic resistance, fish gut, metabolic pathways, microbial diversity

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Authors: Wiam El Kheir, Anais Dumais, Maude Beaudoin, Bernard Marcos, Nick Virgilio, Benoit Paquette, Nathalie Faucheux, Marc-Antoine Lauzon

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The high infiltrative pattern of glioblastoma multiforme cells (GBM) is the main cause responsible for the actual standard treatments failure. The tumor high heterogeneity, the interstitial fluid flow (IFF) and chemokines guides GBM cells migration in the brain parenchyma resulting in tumor recurrence. Drug delivery systems emerged as an alternative approach to develop effective treatments for the disease. Some recent studies have proposed to harness the effect CXC-lchemokine-ligand-12 to direct and control the cancer cell migration through delivery system. However, the dynamics of the brain environment on the delivery system remains poorly understood. Nanoparticles (NPs) and hydrogels are known as good carriers for the encapsulation of different agents and control their release. We studied the release of CXCL12 (free or loaded into NPs) from an alginate-based hydrogel under static and indirect perfusion (IP) conditions. Under static conditions, the main phenomena driving CXCL12 release from the hydrogel was diffusion with the presence of strong interactions between the positively charged CXCL12 and the negatively charge alginate. CXCL12 release profiles were independent from the initial mass loadings. Afterwards, we demonstrated that the release could tuned by loading CXCL12 into Alginate/Chitosan-Nanoparticles (Alg/Chit-NPs) and embedded them into alginate-hydrogel. The initial burst release was substantially attenuated and the overall cumulative release percentages of 21%, 16% and 7% were observed for initial mass loadings of 0.07, 0.13 and 0.26 µg, respectively, suggesting stronger electrostatic interactions. Results were mathematically modeled based on Fick’s second law of diffusion framework developed previously to estimate the effective diffusion coefficient (Deff) and the mass transfer coefficient. Embedding the CXCL12 into NPs decreased the Deff an order of magnitude, which was coherent with experimental data. Thereafter, we developed an in-vitro 3D model that takes into consideration the convective contribution of the brain IFF to study CXCL12 release in an in-vitro microenvironment that mimics as faithfully as possible the human brain. From is unique design, the model also allowed us to understand the effect of IP on CXCL12 release in respect to time and space. Four flow rates (0.5, 3, 6.5 and 10 µL/min) which may increase CXCL12 release in-vivo depending on the tumor location were assessed. Under IP, cumulative percentages varying between 4.5-7.3%, 23-58.5%, 77.8-92.5% and 89.2-95.9% were released for the three initial mass loadings of 0.08, 0.16 and 0.33 µg, respectively. As the flow rate increase, IP culture conditions resulted in a higher release of CXCL12 compared to static conditions as the convection contribution became the main driving mass transport phenomena. Further, depending on the flow rate, IP had a direct impact on CXCL12 distribution within the simulated brain tissue, which illustrates the importance of developing such 3D in-vitro models to assess the efficiency of a delivery system targeting the brain. In future work, using this very model, we aim to understand the impact of the different phenomenon occurring on GBM cell behaviors in response to the resulting chemokine gradient subjected to various flow while allowing them to express their invasive characteristics in an in-vitro microenvironment that mimics the in-vivo brain parenchyma.

Keywords: 3D culture system, chemokines gradient, glioblastoma multiforme, kinetic release, mathematical modeling

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Authors: Casta Guillaume, Robert Jagers, Deborah Rivas-Drake

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Civically engaged youth are critical to maintaining and/or improving the functioning of local, national and global communities and their institutions. The present study investigated how school climate and academic beliefs (academic self-efficacy and school belonging) may inform emergent civic behaviors (emergent citizenship) among self-identified middle school youth of color (African American, Multiracial or Mixed, Latino, Asian American or Pacific Islander, Native American, and other). Study aims: 1) Understand whether and how school climate is associated with civic engagement behaviors, directly and indirectly, by fostering a positive sense of connection to the school and/or engendering feelings of self-efficacy in the academic domain. Accordingly, we examined 2) The association of youths’ sense of school connection and academic self-efficacy with their personally responsible and participatory civic behaviors in school and community contexts—both concurrently and longitudinally. Data from two subsamples of a larger study of social/emotional development among middle school students were used for longitudinal and cross sectional analysis. The cross-sectional sample included 324 6th-8th grade students, of which 43% identified as African American, 20% identified as Multiracial or Mixed, 18% identified as Latino, 12% identified as Asian American or Pacific Islander, 6% identified as Other, and 1% identified as Native American. The age of the sample ranged from 11 – 15 (M = 12.33, SD = .97). For the longitudinal test of our mediation model, we drew on data from the 6th and 7th grade cohorts only (n =232); the ethnic and racial diversity of this longitudinal subsample was virtually identical to that of the cross-sectional sample. For both the cross-sectional and longitudinal analyses, full information maximum likelihood was used to deal with missing data. Fit indices were inspected to determine if they met the recommended thresholds of RMSEA below .05 and CFI and TLI values of at least .90. To determine if particular mediation pathways were significant, the bias-corrected bootstrap confidence intervals for each indirect pathway were inspected. Fit indices for the latent variable mediation model using the cross-sectional data suggest that the hypothesized model fit the observed data well (CFI = .93; TLI =. 92; RMSEA = .05, 90% CI = [.04, .06]). In the model, students’ perceptions of school climate were significantly and positively associated with greater feelings of school connectedness, which were in turn significantly and positively associated with civic engagement. In addition, school climate was significantly and positively associated with greater academic self-efficacy, but academic self-efficacy was not significantly associated with civic engagement. Tests of mediation indicated there was one significant indirect pathway between school climate and civic engagement behavior. There was an indirect association between school climate and civic engagement via its association with sense of school connectedness, indirect association estimate = .17 [95% CI: .08, .32]. The aforementioned indirect association via school connectedness accounted for 50% (.17/.34) of the total effect. Partial support was found for the prediction that students’ perceptions of a positive school climate are linked to civic engagement in part through their role in students’ sense of connection to school.

Keywords: civic engagement, early adolescence, school climate, school belonging, developmental niche

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Authors: Zainab Olabisi Tairu

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The human species is facing some of the most challenging issues encountered as civilization and development occurs. The most salient factors threatening all species globally are habitats loss and degradation, overexploitation, competition with unwanted invasive species, pollution, global climate and various individual lifestyles of indigenous species. In order to avoid or minimize the effect of our actions on the environment and to balance employee work life with their private life, Green Human Resource is important and must be practiced in every organization including Higher Learning Institutions. This study addressed Green HRM from an institutional perspective, University systems are involved in numerous and complex social, educational and extra-curricular activities. The University community must be challenged to rethink and re-construct their environmental policies and practices in order to contribute to sustainable development. Many institutions only look at sustainability from the technology improvement aspect and waste management. People are the principal actors for sustainability development at the institutional level. The aim of the study is to explore the concept of Green Human Resource Management at a case site. Divine Word University (DWU) an Institution of Higher Education that embraced the ‘Printing & Paper use Policy’, also commonly referred to as the ‘paperless policy’, the use of solar as an alternative source of energy, water conservation and improvement in internet technology (IT) with the aim of becoming a green institution in effort to help save the environment. This study used Participatory Action Research as the Overarching methodological framework and Egg of sustainability and Wellbeing as the theoretical perspective in analyzing the data, engaging Case study strategy and a mixed method design at DWU. Focus group interview were conducted with three departments at the University, semi-structure interviews with the senior managers, survey questionnaire administered to students and staff with a sample size of 176 participants, in addition, policy documents were also exploited as extra source of data. Waste management including e-waste appeared to be one of the main concerns at DWU. A vast majority of DWU staff and students expressed the need for their institution to do more on sustainability education. The findings revealed that members of the community are not fully integrated like the Egg of sustainability and wellbeing in order to achieve sustainable development goal. The concept of Green Human Resource Management in Universities lies with the idea that Universities must bear profound responsibilities to manage its stakeholders in an environmental friendly way. Human resource management can help local institutions to recognize the need for changes of lifestyle, production, consumption as well as the end product in order to combat or at least reduce human Induced which produce or aggravate it.

Keywords: sustainability, environmental management, higher education institutions, green human resource management

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Authors: Szerena Vajkovszki

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Our worldwide aging society, especially in developed countries, including members of EU, raise sophisticated sociological and economic issues and challenges to be met. As declining fertility has outstanding influence underlying this trend, numerous studies have attempted to identify, describe, measure and interpret contributing factors of the fertility rate, out of which relatively few revealed the impact of religion. Identified, examined and influential factors affecting birth rate as stated by the present scientific publications are more than a dozen out of which religious beliefs, traditions, and cultural norms were examined first with a special focus on abortion and forms of birth control. Nevertheless, connected to religion, not only these topics are crucial regarding fertility, but many others as well. Among many religious guidelines, we can separate two major categories: direct and indirect. The aim of this research was to understand what are the most crucial identified (family values, gender related behaviors, religious sentiments) and not yet identified most influential contributing religious factors. Above identifying these direct or indirect factors, it is also important to understand to what extent and how do they influence fertility, which requires a wider (inter-discipline) perspective. As proved by previous studies religion has also an influential role on health, mental state, well-being, working activity and many other components that are also related to fertility rates. All these components are inter-related. Hence direct and indirect religious effects can only be well understood if we figure out all necessary fields and their interaction. With the help of semi-structured opened interviews taking place in different countries, it was showed that indeed Buddhism has significant direct and indirect effect on fertility. Hence the initial hypothesis was proved. However, the interviews showed an overall positive effect; the results could only serve for a general understanding of how Buddhism affects fertility. Evolution of Buddhism’s direct and indirect influence may vary in different nations and circumstances according to their specific environmental attributes. According to the local patterns, with special regard to women’s position and role in the society, outstandingly indirect influences could show diversifications. So it is advisory to investigate more for a deeper and clearer understanding of how Buddhism function in different socioeconomic circumstances. For this purpose, a specific and detailed analysis was developed from recent related researches about women’s position (including family roles and economic activity) in Hungary with the intention to be able to have a complex vision of crucial socioeconomic factors influencing fertility. Further interviews and investigations are to be done in order to show a complex vision of Buddhism’s direct and indirect effect on fertility in Hungary to be able to support recommendations and policies pointing to higher fertility rates in the field of social policies. The present research could serve as a general starting point or a common basis for further specific national investigations.

Keywords: Buddhism, children, fertility, gender roles, religion, women

Procedia PDF Downloads 152

Authors: Ning Niu

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The study hinges on consumer taste, food industry (wine production) and cultural consumption (vineyard tourism) which are related to the Chinese market, consumers, and visitors traveling to Australian vineyards. The research topic can be summed up as: the economic importance of the Chinese market on Australian wine production; the economic importance of the Chinese market have an impact on how Australian wine is produced or packaged; the impact of mass Chinese wine tourism on Australian vineyards; the gendered and cultured experience of wine tourism for Chines visitors. This study aims to apply the theories of Pierre Bourdieu into the research in food industry and cultural consumption; investigate Chinese experiences with Australian wine products and vineyard tours; to explore the cultural, gendered and class influences on their experiences. The academic background covers the concepts of habitus, taste, capital proposed by Pierre Bourdieu along with long-lasting concepts within China’s cultural context including mianzi (face, dignity/honor/hierarchy) and guanxi (connections/social network), in order to develop new perspectives to study the tastes of Chinese tourists coming to Australia for wine experiences. The documents cited from Australian government or industries will be interpreted, and the analysis of data will constitute the economic background for this current study. The study applies qualitative research and draws from the fieldwork, choosing ethnographic observation, interviews, personal experiences and discursive analysis of government documents and tourism documents. The expected sample size includes three tourism professionals, two or three local Australian wine producers, and 20 to 30 Chinese wine consumers and visitors travelling to Australian vineyards. An embodied ethnography will be used to observe the Chinese participants’ feelings, thoughts, and experiences of their engagement with Australian wine and vineyards. The researcher will interview with Chinese consumers, tourism professionals, and Australian winemakers to collect primary data. Note-taking, picture-taking, and audio-recording will be adopted with informants’ permissions. Personal or group interview will be last for 30 and 60 minutes respectively. Personal experiences of the researcher have been analyzed to respond to some research questions, and have accumulated part of primary data (e.g., photos and stories) to discover how 'mianzi' and 'guanxi' influence Australian wine and tourism industries to meet the demands’ of Chinese consumers. At current stage, the secondary data from analysis of official and industrial documents has proved the economic importance of Chinese market is influencing Australian wine and tourism industries. And my own experiences related to this study, in some sense, has proved the Chinese cultural concepts (mianzi and guanxi) are influencing the Australian wine production and package along with vineyard tours. Future fieldwork will discover more in this research realm, contribute more to knowledge.

Keywords: habitus, taste, capital, mianzi, guanxi

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Authors: Tesfaldet Mekonnen Estifanos, Chen Hui, Afewerki Weldezgi

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Background: Youth in general and young females in particular, remain at the center of the HIV/AIDS epidemic. Sexual risk-taking among young unmarried women is relatively high and are the most vulnerable and highly exposed to HIV/AIDS. Improvements in the status of HIV/AIDS knowledge and acceptance attitude towards people living with HIV (PLWHIV) plays a great role in averting the incidence of HIV/AIDS. Thus, the aim of the study was to explore the level and correlates of HIV/AIDS knowledge and accepting attitude toward PLWHIV. Methods: A cross-sectional study was conducted using data from the Uganda Demographic Health Survey 2016 (UDHS-2016). National level representative household surveys using a multistage cluster probability sampling method, face to face interviews with standard questionnaires were performed. Unmarried women aged 15-24 years with a sample size of 2019 were selected from the total sample of 8674 women aged 15-49 years and were analyzed using SPSS version 23. Independent variables such as age, religion, educational level, residence, and wealth index were included. Two binary outcome variables (comprehensive HIV/AIDS knowledge and acceptance attitude toward PLWHIV) were utilized. We used the chi-square test as well as multivariate regression analysis to explore correlations of explanatory variables with the outcome variables. The results were reported by odds ratios (OR) with 95% confidence interval (95% CI), taking a p-value less than 0.05 as significant. Results: Almost all (99.3%) of the unmarried women aged 15-24 years were aware of HIV/AIDS, but only 51.2% had adequate comprehensive knowledge on HIV/AIDS. Only 69.4% knew both methods: using a condom every time had sex, and having only one faithful uninfected partner can prevent HIV/AIDS transmission. About 66.6% of the unmarried women reject at least two common local misconceptions about HIV/AIDS. Moreover, an alarmingly few (20.3%) of the respondents had a positive acceptance attitude to PLWHIV. On multivariate analysis, age (20-24 years), living in urban, being educated and wealthier, were predictors of having adequate comprehensive HIV/AIDS knowledge. On the other hand, research participants with adequate comprehensive knowledge about HIV/AIDS were highly likely (OR, 1.94 95% CI, 1.52-2.46) to have a positive acceptance attitude to PLWHIV than those with inadequate knowledge. Respondents with no education, Muslim, and Pentecostal religion were emerged less likely to have a positive acceptance attitude to PLWHIV. Conclusion: This study found out the highly accepted level of awareness, but the knowledge and positive acceptance attitude are not encouraging. Thus, expanding access to comprehensive sexuality and strengthening educational campaigns on HIV/AIDS in communities, health facilities, and schools is needed with a greater focus on disadvantaged women having low educational level, poor socioeconomic status, and those residing in rural areas. Sexual risk behaviors among the most affected people - young women have also a role in the spread of HIV/AIDS. Hence, further research assessing the significant contributing factors for sexual risk-taking might have a positive impact on the fight against HIV/AIDS.

Keywords: acceptance attitude, HIV/AIDS, knowledge, unmarried women

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Authors: Rajesh Kumar Gautam, Debabrata Seth

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Thioflavin-T (ThT) play a key role of an important biologically active fluorescent sensor for amyloid fibrils. ThT molecule has been developed a method to detect the analysis of different type of diseases such as neurodegenerative disorders, Alzheimer’s, Parkinson’s, and type II diabetes. ThT was used as a fluorescent marker to detect the formation of amyloid fibril. In the presence of amyloid fibril, ThT becomes highly fluorescent. ThT undergoes twisting motion around C-C bonds of the two adjacent benzothiazole and dimethylaniline aromatic rings, which is predominantly affected by the micro-viscosity of the local environment. The present study articulates photophysics and torsional dynamics of biologically active molecule ThT in the presence of deep-eutectic solvents (DESs). DESs are environment-friendly, low cost and biodegradable alternatives to the ionic liquids. DES resembles ionic liquids, but the constituents of a DES include a hydrogen bond donor and acceptor species, in addition to ions. Due to the presence of the H-bonding network within a DES, it exhibits structural heterogeneity. Herein, we have prepared two different DESs by mixing urea with choline chloride and N, N-diethyl ethanol ammonium chloride at ~ 340 K. It was reported that deep eutectic mixture of choline chloride with urea gave a liquid with a freezing point of 12°C. We have experimented by taking two different concentrations of ThT. It was observed that at higher concentration of ThT (50 µM) it forms aggregates in DES. The photophysics of ThT as a function of temperature have been explored by using steady-state, and picoseconds time-resolved fluorescence emission spectroscopic techniques. From the spectroscopic analysis, we have observed that with rising temperature the fluorescence quantum yields and lifetime values of ThT molecule gradually decreases; this is the cumulative effect of thermal quenching and increase in the rate of the torsional rate constant. The fluorescence quantum yield and fluorescence lifetime decay values were always higher for DES-II (urea & N, N-diethyl ethanol ammonium chloride) than those for DES-I (urea & choline chloride). This was mainly due to the presence of structural heterogeneity of the medium. This was further confirmed by comparison with the activation energy of viscous flow with the activation energy of non-radiative decay. ThT molecule in less viscous media undergoes a very fast twisting process and leads to deactivation from the photoexcited state. In this system, the torsional motion increases with increasing temperature. We have concluded that beside bulk viscosity of the media, structural heterogeneity of the medium play crucial role to guide the photophysics of ThT in DESs. The analysis of the experimental data was carried out in the temperature range 288 ≤ T = 333K. The present articulate is to obtain an insight into the DESs as media for studying various photophysical processes of amyloid fibrils sensing molecule of ThT.

Keywords: deep eutectic solvent, photophysics, Thioflavin T, the torsional rate constant

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Authors: Gu Sihao

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The coordinated development of "ecology-production-life" in cities has been highly concerned by the country, and the transformation development and sustainable development of resource-based cities have become a hot research topic at present. As an important part of China's resource-based cities, coal resource-based cities have the characteristics of large number and wide distribution. However, due to the adjustment of national energy structure and the gradual exhaustion of urban coal resources, the development vitality of coal resource-based cities is gradually reduced. In many studies, the deterioration of ecological environment in coal resource-based cities has become the main problem restricting their urban transformation and sustainable development due to the "emphasis on economy and neglect of ecology". Since the 18th National Congress of the Communist Party of China (CPC), the Central Government has been deepening territorial space planning and development. On the premise of optimizing territorial space development pattern, it has completed the demarcation of ecological protection red lines, carried out ecological zoning and ecosystem evaluation, which have become an important basis and scientific guarantee for ecological modernization and ecological civilization construction. Grasp the regional multiple ecosystem services is the precondition of the ecosystem management, and the relationship between the multiple ecosystem services study, ecosystem services cluster can identify the interactions between multiple ecosystem services, and on the basis of the characteristics of the clusters on regional ecological function zoning, to better Social-Ecological system management. Based on this cognition, this study optimizes the spatial function zoning of Gujiao, a coal resource-based city, in order to provide a new theoretical basis for its sustainable development. This study is based on the detailed analysis of characteristics and utilization of Gujiao city land space, using SOFM neural networks to identify local ecosystem service clusters, according to the cluster scope and function of ecological function zoning of space partition balance and coordination between different ecosystem services strength, establish a relationship between clusters and land use, and adjust the functions of territorial space within each zone. Then, according to the characteristics of coal resources city and national spatial function zoning characteristics, as the driving factors of land change, by cellular automata simulation program, such as simulation under different restoration strategy situation of urban future development trend, and provides relevant theories and technical methods for the "third-line" demarcations of Gujiao's territorial space planning, optimizes territorial space functions, and puts forward targeted strategies for the promotion of regional ecosystem services, providing theoretical support for the improvement of human well-being and sustainable development of resource-based cities.

Keywords: coal resource-based city, territorial spatial planning, ecosystem service cluster, gmop model, geosos-FLUS model, functional zoning optimization and upgrading

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Authors: Gagandeep Kaur

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The pesticide industry is a big supplier of agricultural inputs. The uses of pesticides control weeds, fungal diseases, etc., which causes of yield losses in agricultural production. In agribusiness and agrichemical industry, Globalization of markets, competition and innovation are the dominant trends. By the tradition of increasing the productivity of agro-systems through generic, universally applicable technologies, innovation in the agrichemical industry is limited. The marketing of technology of agriculture needs to deal with some various trends such as locally-organized forces that envision regionalized sustainable agriculture in the future. Agricultural production has changed dramatically over the past century. Before World War second agricultural production was featured as a low input of money, high labor, mixed farming and low yields. Although mineral fertilizers were applied already in the second half of the 19th century, most f the crops were restricted by local climatic, geological and ecological conditions. After World War second, in the period of reconstruction, political and socioeconomic pressure changed the nature of agricultural production. For a growing population, food security at low prices and securing farmer income at acceptable levels became political priorities. Current agricultural policy the new European common agricultural policy is aimed to reduce overproduction, liberalization of world trade and the protection of landscape and natural habitats. Farmers have to increase the quality of their productivity and they have to control costs because of increased competition from the world market. Pesticides should be more effective at lower application doses, less toxic and not pose a threat to groundwater. There is a big debate taking place about how and whether to mitigate the intensive use of pesticides. This debate is about the future of agriculture which is sustainable agriculture. This is possible by moving away from conventional agriculture. Conventional agriculture is featured as high inputs and high yields. The use of pesticides in conventional agriculture implies crop production in a wide range. To move away from conventional agriculture is possible through the gradual adoption of less disturbing and polluting agricultural practices at the level of the cropping system. For a healthy environment for crop production in the future there is a need for the maintenance of chemical, physical or biological properties. There is also required to minimize the emission of volatile compounds in the atmosphere. Companies are limiting themselves to a particular interpretation of sustainable development, characterized by technological optimism and production-maximizing. So the main objective of the paper will present the trends in the pesticide industry and in agricultural production in the era of Globalization. The second objective is to analyze sustainable agriculture. Companies of pesticides seem to have identified biotechnology as a promising alternative and supplement to the conventional business of selling pesticides. The agricultural sector is in the process of transforming its conventional mode of operation. Some experts give suggestions to farmers to move towards precision farming and some suggest engaging in organic farming. The methodology of the paper will be historical and analytical. Both primary and secondary sources will be used.

Keywords: globalization, pesticides, sustainable development, organic farming

Procedia PDF Downloads 98

Authors: Bosiacki Mateusz, Anna Lubkowska, Dariusz Chlubek, Irena Baranowska-Bosiacka

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Exposure to cold temperatures can be considered a stressor that can lead to adaptive responses. The present study hypothesized the possibility of a positive effect of cold water exercise on mitochondrial biogenesis and muscle energy metabolism in aging rats. The purpose of this study was to evaluate the effects of cold water exercise on energy status, purine compounds, and mitochondrial biogenesis in the muscles of aging rats as indicators of the effects of cold water exercise and their usefulness in monitoring adaptive changes. The study was conducted on 64 aging rats of both sexes, 15 months old at the time of the experiment. The rats (male and female separately) were randomly assigned to the following study groups: control, sedentary animals; 5°C groups animals - training swimming in cold water at 5°C; 36°C groups - animals training swimming in water at thermal comfort temperature. The study was conducted with the approval of the Local Ethical Committee for Animal Experiments. The animals in the experiment were subjected to swimming training for 9 weeks. During the first week of the study, the duration of the first swimming training was 2 minutes (on the first day), increasing daily by 0.5 minutes up to 4 minutes on the fifth day of the first week. From the second to the eighth week, the swimming training was 4 minutes per day, five days a week. At the end of the study, forty-eight hours after the last swim training, the animals were dissected. In the skeletal muscle tissue of the thighs of the rats, we determined the concentrations of ATP, ADP, AMP, Ado (HPLC), PGC-1a protein expression (Western blot), PGC1A, Mfn1, Mfn2, Opa1, and Drp1 gene expression (qRT PCR). The study showed that swimming in water at a thermally comfortable temperature improved the energy metabolism of the aging rat muscles by increasing the metabolic rate (increase in ATP, ADP, TAN, AEC) and enhancing mitochondrial fusion (increase in mRNA expression of regulatory proteins Mfn1 and Mfn2). Cold water swimming improved muscle energy metabolism in aging rats by increasing the rate of muscle energy metabolism (increase in ATP, ADP, TAN, AEC concentrations) and enhancing mitochondrial biogenesis and dynamics (increase in the mRNA expression of proteins of fusion-regulating factors – Mfn1, Mfn2, and Opa1, and the factor regulating mitochondrial fission – Drp1). The concentration of high-energy compounds and the expression of proteins regulating mitochondrial dynamics in the muscle may be a useful indicator in monitoring adaptive changes occurring in aging muscles under the influence of exercise in cold water. It represents a short-term adaptation to changing environmental conditions and has a beneficial effect on maintaining the bioenergetic capacity of muscles in the long term. Conclusion: exercise in cold water can exert positive effects on energy metabolism, biogenesis and dynamics of mitochondria in aging rat muscles. Enhancement of mitochondrial dynamics under cold water exercise conditions can improve mitochondrial function and optimize the bioenergetic capacity of mitochondria in aging rat muscles.

Keywords: cold water immersion, adaptive responses, muscle energy metabolism, aging

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Authors: Shuyi Xie

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As the vital city in south China since the ancient time, Guangzhou has been losing its leading role among the rising neighboring cities, especially, Hong Kong and Shenzhen, since the late 1980s, with the overloaded infrastructure and deteriorating urban environment in its old inner city. Fortunately, with the new expansion of its administrative area in 2000, the local municipality considered it as a great opportunity to solve a series of alarming urban problems. Thus, for the first time, strategic planning was introduced to China for providing more convincing and scientific basis towards better urban future. Differed from traditional Chinese planning practices, which rigidly and dogmatically focused on future blueprints, the strategic planning of Guangzhou proceeded from analyzing practical challenges and opportunities towards establishing reasonable developing objectives and proposing corresponding strategies. Moreover, it was pioneering that the municipality invited five planning institutions for proposals, among which, the paper focuses on the one proposed by China Academy of Urban Planning & Design from its theoretical basis to problems’ defining and analyzing the process, as well as planning results. Since it was closer to the following municipal decisions and had a more far-reaching influence for other Chinese cities' following practices. In particular, it demonstrated an innovative exploration on the role played by urban developing rate on deciding urban growth patterns (‘Spillover-reverberation’ or ‘Leapfrog’). That ultimately established an unprecedented paradigm on deciding an appropriate urban spatial structure in future, including its specific location, function and scale. Besides the proposal itself, this article highlights the role of interactions, among actors, as well as proposals, subsequent discussions, summaries and municipal decisions, especially the establishment of the rolling dynamic evaluation system for periodical reviews on implementation situations, as the first attempt in China. Undoubtedly, strategic planning of Guangzhou has brought out considerable benefits, especially opening the strategic mind for plentiful Chinese cities in the following years through establishing a flexible and dynamic planning mechanism highlighted the interactions among multiple actors with innovative and effective tools, methodologies and perspectives on regional, objective-approach and comparative analysis. However, compared with some developed countries, the strategic planning in China just started and has been greatly relied on empirical studies rather than scientific analysis. Moreover, it still faced a bit of controversy, for instance, the certain gap among institutional proposals, final municipal decisions and implemented results, due to the lacking legal constraint. Also, how to improve the public involvement in China with an absolute up-down administrative system is another urgent task. In future, despite of irresistible and irretrievable weakness, some experiences and lessons from previous international practices, with the combination of specific Chinese situations and domestic practices, would enable to promote the further advance on strategic planning in China.

Keywords: evaluation system, global perspective, Guangzhou, interactions, strategic planning, urban growth patterns

Procedia PDF Downloads 390

Authors: Achraf Al Faraj, Asma Sultana Shaik, Baraa Al Sayed

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Specific and effective targeting of drug delivery systems (DDS) to cancerous sites remains a major challenge for a better diagnostic and therapy. Recently, SWCNTs with their unique physicochemical properties and the ability to cross the cell membrane show promising in the biomedical field. The purpose of this study was first to develop a biocompatible iron oxide tagged SWCNTs as diagnostic nanoprobes to allow their noninvasive detection using MRI and their preferential targeting in a breast cancer murine model by placing an optimized flexible magnet over the tumor site. Magnetic targeting was associated to specific antibody-conjugated SWCNTs active targeting. The therapeutic efficacy of doxorubicin-conjugated SWCNTs was assessed, and the superiority of diffusion-weighted (DW-) MRI as sensitive imaging biomarker was investigated. Short Polyvinylpyrrolidone (PVP) stabilized water soluble SWCNTs were first developed, tagged with iron oxide nanoparticles and conjugated with Endoglin/CD105 monoclonal antibodies. They were then conjugated with doxorubicin drugs. SWCNTs conjugates were extensively characterized using TEM, UV-Vis spectrophotometer, dynamic light scattering (DLS) zeta potential analysis and electron spin resonance (ESR) spectroscopy. Their MR relaxivities (i.e. r1 and r2*) were measured at 4.7T and their iron content and metal impurities quantified using ICP-MS. SWCNTs biocompatibility and drug efficacy were then evaluated both in vitro and in vivo using a set of immunological assays. Luciferase enhanced bioluminescence 4T1 mouse mammary tumor cells (4T1-Luc2) were injected into the right inguinal mammary fat pad of Balb/c mice. Tumor bearing mice received either free doxorubicin (DOX) drug or SWCNTs with or without either DOX or iron oxide nanoparticles. A multi-pole 10x10mm high-energy flexible magnet was maintained over the tumor site during 2 hours post-injections and their properties and polarity were optimized to allow enhanced magnetic targeting of SWCNTs toward the primary tumor site. Tumor volume was quantified during the follow-up investigation study using a fast spin echo MRI sequence. In order to detect the homing of SWCNTs to the main tumor site, susceptibility-weighted multi-gradient echo (MGE) sequence was used to generate T2* maps. Apparent diffusion coefficient (ADC) measurements were also performed as a sensitive imaging biomarker providing early and better assessment of disease treatment. At several times post-SWCNT injection, histological analysis were performed on tumor extracts and iron-loaded SWCNT were quantified using ICP-MS in tumor sites, liver, spleen, kidneys, and lung. The optimized multi-poles magnet revealed an enhanced targeting of magnetic SWCNTs to the primary tumor site, which was found to be much higher than the active targeting achieved using antibody-conjugated SWCNTs. Iron-loading allowed their sensitive noninvasive tracking after intravenous administration using MRI. The active targeting of doxorubicin through magnetic antibody-conjugated SWCNTs nanoprobes was found to considerably decrease the primary tumor site and may have inhibited the development of metastasis in the tumor-bearing mice lung. ADC measurements in DW-MRI were found to significantly increase in a time-dependent manner after the injection of DOX-conjugated SWCNTs complexes.

Keywords: single-walled carbon nanotubes, nanomedicine, magnetic resonance imaging, cancer diagnosis and therapy

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Authors: Wellemans Isabelle, Remmelink Myriam, Foucart Annick, Rusu Stefan, Compère Christophe

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Primary pulmonary meningioma (PPM) is a very rare tumor, and its occurrence has been reported only sporadically. Multiple PPMs are even more exceptional, and herein, we report, to the best of our knowledge, the fourth case, focusing on the clinicopathological features of the tumor. Moreover, the possible relationship between the use of progesterone–only contraceptives and the development of these neoplasms will be discussed. Case Report: We report a case of a 51-year-old female presenting three solid pulmonary nodules, with the following localizations: right upper lobe, middle lobe, and left lower lobe, described as incidental findings on computed tomography (CT) during a pre-bariatric surgery check-up. The patient revealed no drinking or smoking history. The physical exam was unremarkable except for the obesity. The lesions ranged in size between 6 and 24 mm and presented as solid nodules with lobulated contours. The largest lesion situated in the middle lobe had mild fluorodeoxyglucose (FDG) uptake on F-18 FDG positron emission tomography (PET)/CT, highly suggestive of primary lung neoplasm. For pathological assessment, video-assisted thoracoscopic middle lobectomy and wedge resection of the right upper nodule was performed. Histological examination revealed relatively well-circumscribed solid proliferation of bland meningothelial cells growing in whorls and lobular nests, presenting intranuclear pseudo-inclusions and psammoma bodies. No signs of anaplasia were observed. The meningothelial cells expressed diffusely Vimentin, focally Progesterone receptors and were negative for epithelial (cytokeratin (CK) AE1/AE3, CK7, CK20, Epithelial Membrane Antigen (EMA)), neuroendocrine markers (Synaptophysin, Chromogranin, CD56) and Estrogenic receptors. The proliferation labelling index Ki-67 was low (<5%). Metastatic meningioma was ruled out by brain and spine magnetic resonance imaging (MRI) scans. The third lesion localized in the left lower lobe was followed-up and resected three years later because of its slow but significant growth (14 mm to 16 mm), alongside two new infra centimetric lesions. Those three lesions showed a morphological and immunohistochemical profile similar to previously resected lesions. The patient was disease-free one year post-last surgery. Discussion: Although PPMs are mostly benign and slow-growing tumors with an excellent prognosis, they do not present specific radiological characteristics, and it is difficult to differentiate it from other lung tumors, histopathologic examination being essential. Aggressive behavior is associated with atypical or anaplastic features (WHO grades II–III) The etiology is still uncertain and different mechanisms have been proposed. A causal connection between sexual hormones and meningothelial proliferation has long been suspected and few studies examining progesterone only contraception and meningioma risk have all suggested an association. In line with this, our patient was treated with Levonorgestrel, a progesterone agonist, intra-uterine device (IUD). Conclusions: PPM, defined by the typical histological and immunohistochemical features of meningioma in the lungs and the absence of central nervous system lesions, is an extremely rare neoplasm, mainly solitary and associating, and indolent growth. Because of the unspecific radiologic findings, it should always be considered in the differential diagnosis of lung neoplasms. Regarding multiple PPM, only three cases are reported in the literature, and this is the first described in a woman treated by a progesterone-only IUD to the best of our knowledge.

Keywords: pulmonary meningioma, multiple meningioma, meningioma, pulmonary nodules

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Authors: Katarzyna Lubecka, Kirsty Flower, Megan Beetch, Lucinda Kurzava, Hannah Buvala, Samer Gawrieh, Suthat Liangpunsakul, Tracy Gonzalez, George McCabe, Naga Chalasani, James M. Flanagan, Barbara Stefanska

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Hepatocellular carcinoma (HCC), the most prevalent type of primary liver cancer, is the second leading cause of cancer death worldwide. Late onset of clinical symptoms in HCC results in late diagnosis and poor disease outcome. Approximately 85% of individuals with HCC have underlying liver cirrhosis. However, not all cirrhotic patients develop cancer. Reliable early detection biomarkers that can distinguish cirrhotic patients who will develop cancer from those who will not are urgently needed and could increase the cure rate from 5% to 80%. We used Illumina-450K microarray to test whether blood DNA, an easily accessible source of DNA, bear site-specific changes in DNA methylation in response to HCC before diagnosis with conventional tools (pre-diagnostic). Top 11 differentially methylated sites were selected for validation by pyrosequencing. The diagnostic potential of the 11 pyrosequenced probes was tested in blood samples from a prospective cohort of cirrhotic patients. We identified 971 differentially methylated CpG sites in pre-diagnostic HCC cases as compared with healthy controls (P < 0.05, paired Wilcoxon test, ICC ≥ 0.5). Nearly 76% of differentially methylated CpG sites showed lower levels of methylation in cases vs. controls (P = 2.973E-11, Wilcoxon test). Classification of the CpG sites according to their location relative to CpG islands and transcription start site revealed that those hypomethylated loci are located in regulatory regions important for gene transcription such as CpG island shores, promoters, and 5’UTR at higher frequency than hypermethylated sites. Among 735 CpG sites hypomethylated in cases vs. controls, 482 sites were assigned to gene coding regions whereas 236 hypermethylated sites corresponded to 160 genes. Bioinformatics analysis using GO, KEGG and DAVID knowledgebase indicate that differentially methylated CpG sites are located in genes associated with functions that are essential for gene transcription, cell adhesion, cell migration, and regulation of signal transduction pathways. Taking into account the magnitude of the difference, statistical significance, location, and consistency across the majority of matched pairs case-control, we selected 11 CpG loci corresponding to 10 genes for further validation by pyrosequencing. We established that methylation of CpG sites within 5 out of those 10 genes distinguish cirrhotic patients who subsequently developed HCC from those who stayed cancer free (cirrhotic controls), demonstrating potential as biomarkers of early detection in populations at risk. The best predictive value was detected for CpGs located within BARD1 (AUC=0.70, asymptotic significance ˂0.01). Using an additive logistic regression model, we further showed that 9 CpG loci within those 5 genes, that were covered in pyrosequenced probes, constitute a panel with high diagnostic accuracy (AUC=0.887; 95% CI:0.80-0.98). The panel was able to distinguish pre-diagnostic cases from cirrhotic controls free of cancer with 88% sensitivity at 70% specificity. Using blood as a minimally invasive material and pyrosequencing as a straightforward quantitative method, the established biomarker panel has high potential to be developed into a routine clinical test after validation in larger cohorts. This study was supported by Showalter Trust, American Cancer Society (IRG#14-190-56), and Purdue Center for Cancer Research (P30 CA023168) granted to BS.

Keywords: biomarker, DNA methylation, early detection, hepatocellular carcinoma

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Authors: Rajkumar Ghosh, Bhabani Prasad Mukhopadhay

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Rice milling is an important activity in agricultural economy of India, particularly the Burdwan district. However, the environmental impact of rice mills is frequently underestimated. The environmental impact of rice mills in the Burdwan district is a major source of concern, given the importance of rice milling in the local economy and food supply. In the Burdwan district, more than fifty (50) rice mills are in operation. The goal of this study is to investigate the effects of rice mills on several environmental components, with a particular emphasis on groundwater, surface water, soil, and vegetation. The research comprises a thorough review of numerous rice mills located around the district, utilising both qualitative and quantitative approaches. Water samples taken from wells near rice mills will be tested for groundwater quality, with an emphasis on factors such as heavy metal pollution and pollutant concentrations. Monitoring rice mill discharge into neighbouring bodies of water and studying the potential impact on aquatic ecosystems will be part of surface water evaluations. Furthermore, soil samples from the surrounding areas will be taken to examine changes in soil characteristics, nutrient content, and potential contamination from milling waste disposal. Vegetation studies will be conducted to investigate the effects of emissions and effluents on plant health and biodiversity in the region. The findings will provide light on the extent of environmental degradation caused by rice mills in the Burdwan district, as well as valuable insight into the effects of such operations on water, soil, and vegetation. The findings will aid in the development of appropriate legislation and regulations to reduce negative environmental repercussions and promote sustainable practises in the rice milling business. In some cases, heavy metals have been related to health problems. Heavy metals (As, Cd, Cu, Pb, Cr, Hg) are linked to skin, lung, brain, kidney, liver, metabolic, spleen, cardiovascular, haematological, immunological, gastrointestinal, testes, pancreatic, metabolic, and bone problems. As a result, this study contributes to a better knowledge of industrial environmental impacts and establishes the framework for future studies aimed at developing a more ecologically balanced and resilient Burdwan district. The following recommendations are offered for reducing the rice mill's environmental impact: To keep untreated effluents out of bodies of water, adequate waste management systems must be established. Use environmentally friendly rice milling processes to reduce pollution. To avoid soil pollution, rice mill by-products should be used as fertiliser in a controlled and appropriate manner. Groundwater, surface water, soil, and vegetation are all regularly monitored in order to study and adapt to environmental changes. By adhering to these principles, the rice milling industry of Burdwan district may achieve long-term growth while lowering its environmental effect and safeguarding the environment for future generations.

Keywords: groundwater, environmental analysis, biodiversity, rice mill, waste management, diseases, industrial impact

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Authors: Delsy Salinas, Andreia Garcês, Augusto Silva, Paula Brilhante Simões

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Urinary tract infection (UTI) is a common disease affecting dogs and cats in both community and hospital environment. Bacteria is the most frequent agent isolated, fewer than 1% of infections are due to parasitic, fungal, or viral agents. Common symptoms and laboratory abnormalities includeabdominal pain, pyrexia, renomegaly, and neutrophilia with left shift. A rapid and precise identification of the bacterial agent is still a challenge in veterinarian laboratories. Therefore, this cross-sectional study aims to describe bacterial colony patterns of urine samples by using chromID™ CPS® EliteAgar (BioMérieux, France) from canine and feline specimens submitted to a veterinary laboratory in Portugal (INNO Veterinary Laboratory, Braga)from January to March2022. All urine samples were cultivated in CPS Elite Agar with calibrated 1 µL inoculating loop and incubated at 37ºC for 18-24h. Color,size, and shape (regular or irregular outline)were recorded for all samples. All colonies were classified as Gram-negative or Gram-positive bacteriausing Gram stain (PREVI® Color BioMérieux, France) and determined if they were pure colonies. Identification of bacteria species was performed using GP and GN cards inVitek 2® Compact(BioMérieux, France). A total of 256/1003 submitted urine samples presented bacterial growth, from which 172 isolates were included in this study. The sample’s population included 111 dogs (n=45 males and n=66 females) and 61 cats (n=35 males and n=26 females). The most frequent isolated bacteria wasEscherichia coli (44,7%), followed by Proteus mirabilis (13,4%). All Escherichia coli isolates presented red to burgundy colonies, a colony diameter between 2 to 6 mm, and regular or irregular outlines. Similarly, 100% of Proteus mirabilis isolates were dark yellow colonies with a diffuse pigment and the same size and shape as Escherichia coli. White and pink pale colonies where Staphylococcus species exclusively and S. pseudintermedius was the most frequent (8,2 %). Cian to blue colonies were mostly Enterococcusspp. (8,2%) and Streptococcus spp. (4,6%). Beige to brown colonies were Pseudomonas aeruginosa (2,9%) and Citrobacter spp. (1,2%).Klebsiella spp.,Serratia spp. and Enterobacter spp were green colonies. All Gram-positive isolates were 1 to 2 mm diameter long and had a regular outline, meanwhile, Gram-negative rods presented variable patterns. This results showed that theprevalence of E coli and P. mirabilis as uropathogenic agents follows the same trends in Europe as previously described in other studies. Both agents presented a particular color pattern in CPS Elite Agar to identify them without needing complementary tests. No other bacteria genus could be correlated strongly to a specific color pattern, and similar results have been observed instudies using human’s samples. Chromogenic media shows a great advantage for common urine bacteria isolation than traditional COS, McConkey, and CLEDAgar mediums in a routine context, especially when mixed fermentative Gram-negative agents grow simultaneously. In addition, CPS Elite Agar is versatile for Artificial Intelligent Reading Plates Systems. Routine veterinarian laboratories could use CPS Elite Agar for a rapid screening for bacteria identification,mainlyE coli and P.mirabilis, saving 6h to 10h of automatized identification.

Keywords: cats, CPS elite agar, dogs, urine pathogens

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Authors: Nkeiruka Elsie Ezomike, Chinwe L. Onyekonwu, Anthony N. Ikefuna, Bede C. Ibe

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Superficial fungal infections (SFIs) are one of the common cutaneous infections that affect children worldwide. They may lead to school absenteeism or school drop-out and hence setback in the education of the child. Community-based studies in any locality are good reflections of the health conditions within that area. There is a dearth of information in the literature about SFI among primary school children in Enugu. This study aimed to determine the clinicomycological pattern of SFIs among primary school children in rural and urban communities in Enugu. This was a comparative descriptive cross-sectional study among primary school children in Awgu (rural) and Enugu North (urban) Local Government Areas (LGAs). Subjects' selection was made over 6 months using a multi-stage sampling method. Information such as age, sex, parental education, and occupation were collected using questionnaires. Socioeconomic classes of the children were determined using the classification proposed by Oyedeji et al. The samples were collected from subjects with SFIs. Potassium hydroxide tests were done on the samples. The samples that tested positive were cultured for SFI by inoculating onto Sabouraud's dextrose chloramphenicol actidione agar. The characteristics of the isolates were identified according to their morphological features using Mycology Online, Atlas 2000, and Mycology Review 2003. Equal numbers of children were recruited from the two LGAs. A total of 1662 pupils were studied. The mean ages of the study subjects were 9.03 ± 2.10years in rural and 10.46 ± 2.33years in urban communities. The male to female ratio was 1.6:1 in rural and 1:1.1 in urban communities. The personal hygiene of the children was significantly related to the presence of SFIs. The overall prevalence of SFIs among the study participants was 45%. In the rural, the prevalence was 29.6%, and in the urban prevalence was 60.4%. The types of SFIs were tinea capitis (the commonest), tinea corporis, pityriasis Versicolor, tinea unguium, and tinea manuum with prevalence rates lower in rural than urban communities. The clinical patterns were gray patch and black dot type of non-inflammatory tinea capitis, kerion, tinea corporis with trunk and limb distributions, and pityriasis Versicolor with face, trunk and limb distributions. Gray patch was the most frequent pattern of SFI seen in rural and urban communities. Black dot type was more frequent in rural than urban communities. SFIs were frequent among children aged 5 to 8years in rural and 9 to 12 years in urban communities. SFIs were commoner in males in the rural, whereas female dominance was observed in the urban. SFIs were more in children from low social class and those with poor hygiene. Trichophyton tonsurans and Trichophyton soudanese were the common mycological isolates in rural and urban communities, respectively. In conclusion, SFIs were less prevalent in rural than in urban communities. Trichophyton species were the most common fungal isolates in the communities. Health education of mothers and their children on SFI and good personal hygiene will reduce the incidence of SFIs.

Keywords: clinicomycological pattern, communities, primary school children, superficial fungal infections

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Authors: Jiaying Zhang, Xin Mu, Chang Ni, Jeff L. Zhang

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Magnetic resonance elastography (MRE) non-invasively assesses tissue elastic properties, such as shear modulus, by measuring tissue’s displacement in response to mechanical waves. The estimated metrics on tissue elasticity or stiffness have been shown to be valuable for monitoring physiologic or pathophysiologic status of tissue, such as a tumor or fatty liver. To quantify tissue shear modulus from MRE-acquired displacements (essentially an inverse problem), multiple approaches have been proposed, including Local Frequency Estimation (LFE) and Direct Inversion (DI). However, one common problem with these methods is that the estimates are severely noise-sensitive due to either the inverse-problem nature or noise propagation in the pixel-by-pixel process. With the advent of deep learning (DL) and its promise in solving inverse problems, a few groups in the field of MRE have explored the feasibility of using DL methods for quantifying shear modulus from MRE data. Most of the groups chose to use real MRE data for DL model training and to cut training images into smaller patches, which enriches feature characteristics of training data but inevitably increases computation time and results in outcomes with patched patterns. In this study, simulated wave images generated by Finite Differential Time Domain (FDTD) simulation are used for network training, and U-Net is used to extract features from each training image without cutting it into patches. The use of simulated data for model training has the flexibility of customizing training datasets to match specific applications. The proposed method aimed to estimate tissue shear modulus from MRE data with high robustness to noise and high model-training efficiency. Specifically, a set of 3000 maps of shear modulus (with a range of 1 kPa to 15 kPa) containing randomly positioned objects were simulated, and their corresponding wave images were generated. The two types of data were fed into the training of a U-Net model as its output and input, respectively. For an independently simulated set of 1000 images, the performance of the proposed method against DI and LFE was compared by the relative errors (root mean square error or RMSE divided by averaged shear modulus) between the true shear modulus map and the estimated ones. The results showed that the estimated shear modulus by the proposed method achieved a relative error of 4.91%±0.66%, substantially lower than 78.20%±1.11% by LFE. Using simulated data, the proposed method significantly outperformed LFE and DI in resilience to increasing noise levels and in resolving fine changes of shear modulus. The feasibility of the proposed method was also tested on MRE data acquired from phantoms and from human calf muscles, resulting in maps of shear modulus with low noise. In future work, the method’s performance on phantom and its repeatability on human data will be tested in a more quantitative manner. In conclusion, the proposed method showed much promise in quantifying tissue shear modulus from MRE with high robustness and efficiency.

Keywords: deep learning, magnetic resonance elastography, magnetic resonance imaging, shear modulus estimation

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Authors: Ankur Chaudhuri, Sibani Sen Chakraborty

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In human, glutaminyl cyclase activity is highly abundant in neuronal and secretory tissues and is preferentially restricted to hypothalamus and pituitary. The N-terminal modification of β-amyloids (Aβs) peptides by the generation of a pyro-glutamyl (pGlu) modified Aβs (pE-Aβs) is an important process in the initiation of the formation of neurotoxic plaques in Alzheimer’s disease (AD). This process is catalyzed by glutaminyl cyclase (QC). The expression of QC is characteristically up-regulated in the early stage of AD, and the hallmark of the inhibition of QC is the prevention of the formation of pE-Aβs and plaques. A computer-aided drug design (CADD) process was employed to give an idea for the designing of potentially active compounds to understand the inhibitory potency against human glutaminyl cyclase (QC). This work elaborates the ligand-based and structure-based pharmacophore exploration of glutaminyl cyclase (QC) by using the known inhibitors. Three dimensional (3D) quantitative structure-activity relationship (QSAR) methods were applied to 154 compounds with known IC50 values. All the inhibitors were divided into two sets, training-set, and test-sets. Generally, training-set was used to build the quantitative pharmacophore model based on the principle of structural diversity, whereas the test-set was employed to evaluate the predictive ability of the pharmacophore hypotheses. A chemical feature-based pharmacophore model was generated from the known 92 training-set compounds by HypoGen module implemented in Discovery Studio 2017 R2 software package. The best hypothesis was selected (Hypo1) based upon the highest correlation coefficient (0.8906), lowest total cost (463.72), and the lowest root mean square deviation (2.24Å) values. The highest correlation coefficient value indicates greater predictive activity of the hypothesis, whereas the lower root mean square deviation signifies a small deviation of experimental activity from the predicted one. The best pharmacophore model (Hypo1) of the candidate inhibitors predicted comprised four features: two hydrogen bond acceptor, one hydrogen bond donor, and one hydrophobic feature. The Hypo1 was validated by several parameters such as test set activity prediction, cost analysis, Fischer's randomization test, leave-one-out method, and heat map of ligand profiler. The predicted features were then used for virtual screening of potential compounds from NCI, ASINEX, Maybridge and Chembridge databases. More than seven million compounds were used for this purpose. The hit compounds were filtered by drug-likeness and pharmacokinetics properties. The selective hits were docked to the high-resolution three-dimensional structure of the target protein glutaminyl cyclase (PDB ID: 2AFU/2AFW) to filter these hits further. To validate the molecular docking results, the most active compound from the dataset was selected as a reference molecule. From the density functional theory (DFT) study, ten molecules were selected based on their highest HOMO (highest occupied molecular orbitals) energy and the lowest bandgap values. Molecular dynamics simulations with explicit solvation systems of the final ten hit compounds revealed that a large number of non-covalent interactions were formed with the binding site of the human glutaminyl cyclase. It was suggested that the hit compounds reported in this study could help in future designing of potent inhibitors as leads against human glutaminyl cyclase.

Keywords: glutaminyl cyclase, hit lead, pharmacophore model, simulation

Procedia PDF Downloads 131

Authors: Emily Moskwa, Delene Weber, Jacob Arnold, Guy M. Robinson, Douglas K. Bardsley

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Management strategies to reduce the risks to human life and property from wildfire are key contemporary concerns, with a growing literature exploring these issues from a social research perspective. Efforts range from narrowly focused examinations, such as comparing the level of community support for vegetation clearance with that of controlled burning, to broader considerations of what constitutes effective fire management policy and education campaigns. However, little analysis is available that integrates the social component of risk mitigation and the influence of educational materials with the biodiversity conservation strategies so often needed in fire-prone ecosystems found on the periphery of urban areas. Indeed many communities living on the fringe of Australian cities face major issues relating to an increased risk of wildfire events and a decline in local biodiversity. Inadequate policy and planning, and a lack of awareness or information, exacerbate this risk. This has brought forward an emerging governance challenge that requires the mitigation of wildfire risk while simultaneously supporting improved conservation practices in these urban-fringe areas. Focusing on the perceptions and experiences of residents of the Lower Eyre Peninsula in South Australia, this study analyses data collected from a series of semi-structured interviews with landholders (n=20) living in rural and urban-fringe areas surrounding the city of Port Lincoln, a city with a growing population and one that has faced a number of very large fires in recent years. In South Australia, new policies have assigned increased responsibility on individual landholders to manage their land and prepare themselves for a wildfire event, potentially to the detriment of the surrounding native vegetation. Our findings indicate the value of gaining a more nuanced understanding of the perceptions and behaviours of landholders living in areas of high fire risk, who often choose to live there in order to be close to the natural environment. Many interviewees demonstrated a high awareness of wildfire risk as a result of their past experience with fire, and the majority considered themselves to be well-prepared in the event of a future fire. Community interactions and educational programs were found to be effective in raising awareness of risk; however, negative trust relationships with government authorities and low exposure to information concerning biodiversity resulted in an overall misunderstanding of the relationship between risk mitigation and biodiversity protection. The study offers insights into how catastrophic fires are reframing perceptions of what constitutes effective vegetation management. It provides recommendations to assist with the development of education strategies that concurrently address wildfire management and biodiversity conservation, and contribute towards environmentally-informed and risk conscious governance.

Keywords: biodiversity conservation, risk, peri-urban planning, wildfire management

Procedia PDF Downloads 250