Search results for: complex society

Authors: Pia Ulvenblad, Henrik Barth, Jennie Cederholm BjöRklund, Maya Hoveskog, Per-Ola Ulvenblad

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The importance of business model innovation (BMI) is widely recognized. This is also valid for firms in the agri-food industry, closely connected to global challenges. Worldwide food production will have to increase 70% by 2050 and the United Nations’ sustainable development goals prioritize research and innovation on food security and sustainable agriculture. The firms of the agri-food industry have opportunities to increase their competitive advantage through BMI. However, the process of BMI is complex and the implementation of new business models is associated with high degree of risk and failure. Thus, managers from all industries and scholars need to better understand how to address this complexity. Therefore, the research presented in this paper (i) explores different categories of barriers in research literature on business models in the agri-food industry, and (ii) illustrates categories of barriers with empirical cases. This study is addressing the rather limited understanding on barriers for BMI in the agri-food industry, through a systematic literature review (SLR) of 570 peer-reviewed journal articles that contained a combination of ‘BM’ or ‘BMI’ with agriculture-related and food-related terms (e.g. ‘agri-food sector’) published in the period 1990-2014. The study classifies the barriers in several categories and illustrates the identified barriers with ten empirical cases. Findings from the literature review show that barriers are mainly identified as outcomes. It can be assumed that a perceived barrier to growth can often be initially exaggerated or underestimated before being challenged by appropriate measures or courses of action. What may be considered by the public mind to be a barrier could in reality be very different from an actual barrier that needs to be challenged. One way of addressing barriers to growth is to define barriers according to their origin (internal/external) and nature (tangible/intangible). The framework encompasses barriers related to the firm (internal addressing in-house conditions) or to the industrial or national levels (external addressing environmental conditions). Tangible barriers can include asset shortages in the area of equipment or facilities, while human resources deficiencies or negative willingness towards growth are examples of intangible barriers. Our findings are consistent with previous research on barriers for BMI that has identified human factors barriers (individuals’ attitudes, histories, etc.); contextual barriers related to company and industry settings; and more abstract barriers (government regulations, value chain position, and weather). However, human factor barriers – and opportunities - related to family-owned businesses with idealistic values and attitudes and owning the real estate where the business is situated, are more frequent in the agri-food industry than other industries. This paper contributes by generating a classification of the barriers for BMI as well as illustrating them with empirical cases. We argue that internal barriers such as human factors barriers; values and attitudes are crucial to overcome in order to develop BMI. However, they can be as hard to overcome as for example institutional barriers such as governments’ regulations. Implications for research and practice are to focus on cognitive barriers and to develop the BMI capability of the owners and managers of agri-industry firms.

Keywords: agri-food, barriers, business model, innovation

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Authors: Alena Kulikova, Leonid Parmaksiz, Ekaterina Orel

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Social and emotional skills are considered by modern researchers as predictors of a person's success both in specific areas of activity and in the life of a person as a whole. The popularity of this scientific direction ensures the emergence of a large number of practices aimed at developing and evaluating socio-emotional skills. Assessment of social and emotional development is carried out at the national level, as well as at the level of individual regions and institutions. Despite the fact that many of the already existing social and emotional skills assessment tools are quite convenient and reliable, there are now more and more new technologies and task formats which improve the basic characteristics of the tools. Thus, the goal of the current study is to develop a tool for assessing social and emotional skills such as emotion recognition, emotion regulation, empathy and a culture of self-care. To develop a tool assessing social and emotional skills, Rasch-Gutman scenario-based approach was used. This approach has shown its reliability and merit for measuring various complex constructs: parental involvement; teacher practices that support cultural diversity and equity; willingness to participate in the life of the community after psychiatric rehabilitation; educational motivation and others. To assess emotion recognition, we used a situational judgment task based on OCC (Ortony, Clore, and Collins) emotions theory. The main advantage of these two approaches compare to classical Likert scales is that it reduces social desirability in answers. A field test to check the psychometric properties of the developed instrument was conducted. The instrument was developed for the presidential autonomous non-profit organization “Russia - Land of Opportunity” for nationwide soft skills assessment among higher education students. The sample for the field test consisted of 500 people, students aged from 18 to 25 (mean = 20; standard deviation 1.8), 71% female. 67% of students are only studying and are not currently working and 500 employed adults aged from 26 to 65 (mean = 42.5; SD 9), 57% female. Analysis of the psychometric characteristics of the scales was carried out using the methods of IRT (Item Response Theory). A one-parameter rating scale model RSM (Rating scale model) and Graded Response model (GRM) of the modern testing theory were applied. GRM is a polyatomic extension of the dichotomous two-parameter model of modern testing theory (2PL) based on the cumulative logit function for modeling the probability of a correct answer. The validity of the developed scales was assessed using correlation analysis and MTMM (multitrait-multimethod matrix). The developed instrument showed good psychometric quality and can be used by HR specialists or educational management. The detailed results of a psychometric study of the quality of the instrument, including the functioning of the tasks of each scale, will be presented. Also, the results of the validity study by MTMM analysis will be discussed.

Keywords: social and emotional skills, psychometrics, MTMM, IRT

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Authors: Berengere Vire, Nicolas Salvetat, Yoann Lannay, Guillaume Marcellin, Siem Van Der Laan, Franck Molina, Dinah Weissmann

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Predicting suicidal behaviors is one of the most complex challenges of daily psychiatric practices. Today, suicide risk prediction using biological tools is not validated and is only based on subjective clinical reports of the at-risk individual. Therefore, there is a great need to identify biomarkers that would allow early identification of individuals at risk of suicide. Alterations of adenosine-to-inosine (A-to-I) RNA editing of neurotransmitter receptors and other proteins have been shown to be involved in etiology of different psychiatric disorders and linked to suicidal behavior. RNA editing is a co- or post-transcriptional process leading to a site-specific alteration in RNA sequences. It plays an important role in the epi transcriptomic regulation of RNA metabolism. On postmortem human brain tissue (prefrontal cortex) of depressed suicide victims, Alcediag found specific alterations of RNA editing activity on the mRNA coding for the serotonin 2C receptor (5-HT2cR). Additionally, an increase in expression levels of ADARs, the RNA editing enzymes, and modifications of RNA editing profiles of prime targets, such as phosphodiesterase 8A (PDE8A) mRNA, have also been observed. Interestingly, the PDE8A gene is located on chromosome 15q25.3, a genomic region that has recurrently been associated with the early-onset major depressive disorder (MDD). In the current study, we examined whether modifications in RNA editing profile of prime targets allow identifying disease-relevant blood biomarkers and evaluating suicide risk in patients. To address this question, we performed a clinical study to identify an RNA editing signature in blood of depressed patients with and without the history of suicide attempts. Patient’s samples were drawn in PAXgene tubes and analyzed on Alcediag’s proprietary RNA editing platform using next generation sequencing technology. In addition, gene expression analysis by quantitative PCR was performed. We generated a multivariate algorithm comprising various selected biomarkers to detect patients with a high risk to attempt suicide. We evaluated the diagnostic performance using the relative proportion of PDE8A mRNA editing at different sites and/or isoforms as well as the expression of PDE8A and the ADARs. The significance of these biomarkers for suicidality was evaluated using the area under the receiver-operating characteristic curve (AUC). The generated algorithm comprising the biomarkers was found to have strong diagnostic performances with high specificity and sensitivity. In conclusion, we developed tools to measure disease-specific biomarkers in blood samples of patients for identifying individuals at the greatest risk for future suicide attempts. This technology not only fosters patient management but is also suitable to predict the risk of drug-induced psychiatric side effects such as iatrogenic increase of suicidal ideas/behaviors.

Keywords: blood biomarker, next-generation-sequencing, RNA editing, suicide

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Authors: A. K. Tekile, I. L. Kim, J. Y. Lee

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Human activities put freshwater quality under risk, mainly due to expansion of agriculture and industries, damming, diversion and discharge of inadequately treated wastewaters. The rapid human population growth and climate change escalated the problem. External controlling actions on point and non-point pollution sources are long-term solution to manage water quality. To have a holistic approach, these mechanisms should be coupled with the in-water control strategies. The available in-lake or river methods are either costly or they have some adverse effect on the ecological system that the search for an alternative and effective solution with a reasonable balance is still going on. This study aimed at the physical and chemical water quality improvement in a stagnant Yeo-cheon River reach (Korea), which has recently shown sign of water quality problems such as scum formation and fish death. The river water quality was monitored, for the duration of three months by operating only water flow generator in the first two weeks and then ultrasonic irradiation device was coupled to the flow unit for the remaining duration of the experiment. In addition to assessing the water quality improvement, the correlation among the parameters was analyzed to explain the contribution of the ultra-sonication. Generally, the combined strategy showed localized improvement of water quality in terms of dissolved oxygen, Chlorophyll-a and dissolved reactive phosphate. At locations under limited influence of the system operation, chlorophyll-a was highly increased, but within 25 m of operation the low initial value was maintained. The inverse correlation coefficient between dissolved oxygen and chlorophyll-a decreased from 0.51 to 0.37 when ultrasonic irradiation unit was used with the flow, showing that ultrasonic treatment reduced chlorophyll-a concentration and it inhibited photosynthesis. The relationship between dissolved oxygen and reactive phosphate also indicated that influence of ultra-sonication was higher than flow on the reactive phosphate concentration. Even though flow increased turbidity by suspending sediments, ultrasonic waves canceled out the effect due to the agglomeration of suspended particles and the follow-up settling out. There has also been variation of interaction in the water column as the decrease of pH and dissolved oxygen from surface to the bottom played a role in phosphorus release into the water column. The variation of nitrogen and dissolved organic carbon concentrations showed mixed trend probably due to the complex chemical reactions subsequent to the operation. Besides, the intensive rainfall and strong wind around the end of the field trial had apparent impact on the result. The combined effect of water flow and ultrasonic irradiation was a cumulative water quality improvement and it maintained the dissolved oxygen and chlorophyll-a requirement of the river for healthy ecological interaction. However, the overall improvement of water quality is not guaranteed as effectiveness of ultrasonic technology requires long-term monitoring of water quality before, during and after treatment. Even though, the short duration of the study conducted here has limited nutrient pattern realization, the use of ultrasound at field scale to improve water quality is promising.

Keywords: stagnant, ultrasonic irradiation, water flow, water quality

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Authors: Maria M. Calheiros, Carla Silva, Eunice Magalhães

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Professionals working in child protection services (CPS) need to have common and clear criteria to identify cases of maltreatment and to differentiate levels of severity in order to determine when CPS intervention is required, its nature and urgency, and, in most countries, the service that will be in charge of the case (community or specialized CPS). Actually, decision-making process is complex in CPS, and, for that reason, such criteria are particularly important for who significantly contribute to that decision-making in child maltreatment cases. The main objective of this presentation is to describe the Maltreatment Severity Assessment Questionnaire (MSQ), specifically designed to be used by professionals in the CPS, which adopts a multidimensional approach and uses a scale of severity within subtypes. Specifically, we aim to provide evidence of validity and reliability of this tool, in order to improve the quality and validity of assessment processes and, consequently, the decision making in CPS. The total sample was composed of 1000 children and/or adolescents (51.1% boys), aged between 0 and 18 years old (M = 9.47; DP = 4.51). All the participants were referred to official institutions of the children and youth protective system. Children and adolescents maltreatment (abuse, neglect experiences and sexual abuse) were assessed with 21 items of the Maltreatment Severity Questionnaire (MSQ), by professionals of CPS. Each item (sub-type) was composed of four descriptors of increasing severity. Professionals rated the level of severity, using a 4-point scale (1= minimally severe; 2= moderately severe; 3= highly severe; 4= extremely severe). The construct validity of the Maltreatment Severity Questionnaire was assessed with a holdout method, performing an Exploratory Factor Analysis (EFA) followed by a Confirmatory Factor Analysis (CFA). The final solution comprised 18 items organized in three factors 47.3% of variance explained. ‘Physical neglect’ (eight items) was defined by parental omissions concerning the insurance and monitoring of the child’s physical well-being and health, namely in terms of clothing, hygiene, housing conditions and contextual environmental security. ‘Physical and Psychological Abuse’ (four items) described abusive physical and psychological actions, namely, coercive/punitive disciplinary methods, physically violent methods or verbal interactions that offend and denigrate the child, with the potential to disrupt psychological attributes (e.g., self-esteem). ‘Psychological neglect’ (six items) involved omissions related to children emotional development, mental health monitoring, school attendance, development needs, as well as inappropriate relationship patterns with attachment figures. Results indicated a good reliability of all the factors. The assessment of child maltreatment cases with MSQ could have a set of practical and research implications: a) It is a valid and reliable multidimensional instrument to measure child maltreatment, b) It is an instrument integrating the co-occurrence of various types of maltreatment and a within-subtypes scale of severity; c) Specifically designed for professionals, it may assist them in decision-making processes; d) More than using case file reports to evaluate maltreatment experiences, researchers could guide more appropriately their research about determinants and consequences of maltreatment.

Keywords: assessment, maltreatment, children and youth, decision-making

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Authors: D. Malouch, M. Berchel, C. Dreanno, S. Stachowski-Haberkorn, P-A. Jaffres

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Biofouling is a complex natural phenomenon that involves biological, physical and chemical properties related to the environment, the submerged surface and the living organisms involved. Bio-colonization of artificial structures can cause various economic and environmental impacts. The increase in costs associated with the over-consumption of fuel from biocolonized vessels has been widely studied. Measurement drifts from submerged sensors, as well as obstructions in heat exchangers, and deterioration of offshore structures are major difficulties that industries are dealing with. Therefore, surfaces that inhibit biocolonization are required in different areas (water treatment, marine paints, etc.) and many efforts have been devoted to produce efficient and eco-compatible antifouling agents. The different steps of surface fouling are widely described in literature. Studying the biofilm and its stages provides a better understanding of how to elaborate more efficient antifouling strategies. Several approaches are currently applied, such as the use of biocide anti-fouling paint (mainly with copper derivatives) and super-hydrophobic coatings. While these two processes are proving to be the most effective, they are not entirely satisfactory, especially in a context of a changing legislation. Nowadays, the challenge is to prevent biofouling with non-biocide compounds, offering a cost effective solution, but with no toxic effects on marine organisms. Since the micro-fouling phase plays an important role in the regulation of the following steps of biofilm formation, it is desired to reduce or delate biofouling of a given surface by inhibiting the micro-fouling at its early stages. In our recent works, we reported that some amphiphilic compounds exhibited bacteriostatic or bactericidal properties at a concentration that did not affect mammalian eukaryotic cells. These remarkable properties invited us to assess this type of bio-inspired phospholipids to prevent the colonization of surfaces by marine bacteria. Of note, other studies reported that amphiphilic compounds interacted with bacteria leading to a reduction of their development. An amphiphilic compound is a molecule consisting of a hydrophobic domain and a polar head (ionic or non-ionic). These compounds appear to have interesting antifouling properties: some ionic compounds have shown antimicrobial activity, and zwitterions can reduce nonspecific adsorption of proteins. Herein, we investigate the potential of amphiphilic compounds as inhibitors of bacterial growth and marine biofilm formation. The aim of this study is to compare the efficacy of four synthetic phospholipids that features a cationic charge or a zwitterionic polar-head group to prevent microfouling with marine bacteria. Toxicity of these compounds was also studied in order to identify the most promising compounds that inhibit biofilm development and show low cytotoxicity on two links representative of coastal marine food webs: phytoplankton and oyster larvae.

Keywords: amphiphilic phospholipids, biofilm, marine fouling, non-toxique assays

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Authors: Hongmei Wang, Ziyun Xiang, Ying liu, Li Yu, Dongsheng Yue

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Intro: The COVID-19 (Corona Virus Disease 2019) has greatly changed the global economic, political and financial ecology. The mutation of the coronavirus in the UK in December 2020 has brought new panic to the world. Deep learning was performed on Chest Computed tomography (CT) of COVID-19 and Influenza and describes their characteristics. The predominant features of COVID-19 pneumonia was ground-glass opacification, followed by consolidation. Lesion density: most lesions appear as ground-glass shadows, and some lesions coexist with solid lesions. Lesion distribution: the focus is mainly on the dorsal side of the periphery of the lung, with the lower lobe of the lungs as the focus, and it is often close to the pleura. Other features it has are grid-like shadows in ground glass lesions, thickening signs of diseased vessels, air bronchi signs and halo signs. The severe disease involves whole bilateral lungs, showing white lung signs, air bronchograms can be seen, and there can be a small amount of pleural effusion in the bilateral chest cavity. At the same time, this year's flu season could be near its peak after surging throughout the United States for months. Chest CT for Influenza infection is characterized by focal ground glass shadows in the lungs, with or without patchy consolidation, and bronchiole air bronchograms are visible in the concentration. There are patchy ground-glass shadows, consolidation, air bronchus signs, mosaic lung perfusion, etc. The lesions are mostly fused, which is prominent near the hilar and two lungs. Grid-like shadows and small patchy ground-glass shadows are visible. Deep neural networks have great potential in image analysis and diagnosis that traditional machine learning algorithms do not. Method: Aiming at the two major infectious diseases COVID-19 and influenza, which are currently circulating in the world, the chest CT of patients with two infectious diseases is classified and diagnosed using deep learning algorithms. The residual network is proposed to solve the problem of network degradation when there are too many hidden layers in a deep neural network (DNN). The proposed deep residual system (ResNet) is a milestone in the history of the Convolutional neural network (CNN) images, which solves the problem of difficult training of deep CNN models. Many visual tasks can get excellent results through fine-tuning ResNet. The pre-trained convolutional neural network ResNet is introduced as a feature extractor, eliminating the need to design complex models and time-consuming training. Fastai is based on Pytorch, packaging best practices for in-depth learning strategies, and finding the best way to handle diagnoses issues. Based on the one-cycle approach of the Fastai algorithm, the classification diagnosis of lung CT for two infectious diseases is realized, and a higher recognition rate is obtained. Results: A deep learning model was developed to efficiently identify the differences between COVID-19 and influenza using chest CT.

Keywords: COVID-19, Fastai, influenza, transfer network

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Authors: Andres Nieto-Leal, Victor N. Kaliakin, Tania P. Molina

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The nature of most engineering materials is quite complex. It is, therefore, difficult to devise a general mathematical model that will cover all possible ranges and types of excitation and behavior of a given material. As a result, the development of mathematical models is based upon simplifying assumptions regarding material behavior. Such simplifications result in some material idealization; for example, one of the simplest material idealization is to assume that the material behavior obeys the elasticity. However, soils are nonhomogeneous, anisotropic, path-dependent materials that exhibit nonlinear stress-strain relationships, changes in volume under shear, dilatancy, as well as time-, rate- and temperature-dependent behavior. Over the years, many constitutive models, possessing different levels of sophistication, have been developed to simulate the behavior geomaterials, particularly cohesive soils. Early in the development of constitutive models, it became evident that elastic or standard elastoplastic formulations, employing purely isotropic hardening and predicated in the existence of a yield surface surrounding a purely elastic domain, were incapable of realistically simulating the behavior of geomaterials. Accordingly, more sophisticated constitutive models have been developed; for example, the bounding surface elastoplasticity. The essence of the bounding surface concept is the hypothesis that plastic deformations can occur for stress states either within or on the bounding surface. Thus, unlike classical yield surface elastoplasticity, the plastic states are not restricted only to those lying on a surface. Elastoplastic bounding surface models have been improved; however, there is still need to improve their capabilities in simulating the response of anisotropically consolidated cohesive soils, especially the response in extension tests. Thus, in this work an improved constitutive model that can more accurately predict diverse stress-strain phenomena exhibited by cohesive soils was developed. Particularly, an improved rotational hardening rule that better simulate the response of cohesive soils in extension. The generalized definition of the bounding surface model provides a convenient and elegant framework for unifying various previous versions of the model for anisotropically consolidated cohesive soils. The Generalized Bounding Surface Model for cohesive soils is a fully three-dimensional, time-dependent model that accounts for both inherent and stress induced anisotropy employing a non-associative flow rule. The model numerical implementation in a computer code followed an adaptive multistep integration scheme in conjunction with local iteration and radial return. The one-step trapezoidal rule was used to get the stiffness matrix that defines the relationship between the stress increment and the strain increment. After testing the model in simulating the response of cohesive soils through extensive comparisons of model simulations to experimental data, it has been shown to give quite good simulations. The new model successfully simulates the response of different cohesive soils; for example, Cardiff Kaolin, Spestone Kaolin, and Lower Cromer Till. The simulated undrained stress paths, stress-strain response, and excess pore pressures are in very good agreement with the experimental values, especially in extension.

Keywords: bounding surface elastoplasticity, cohesive soils, constitutive model, modeling of geomaterials

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Authors: James Semmens, James Boyd, Anna Ferrante, Katrina Spilsbury, Sean Randall, Adrian Brown

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‘Big data’ is a relatively new concept that describes data so large and complex that it exceeds the storage or computing capacity of most systems to perform timely and accurate analyses. Health services generate large amounts of data from a wide variety of sources such as administrative records, electronic health records, health insurance claims, and even smart phone health applications. Health data is viewed in Australia and internationally as highly sensitive. Strict ethical requirements must be met for the use of health data to support health research. These requirements differ markedly from those imposed on data use from industry or other government sectors and may have the impact of reducing the capacity of health data to be incorporated into the real time demands of the Big Data environment. This ‘big data revolution’ is increasingly supported by national governments, who have invested significant funds into initiatives designed to develop and capitalize on big data and methods for data integration using record linkage. The benefits to health following research using linked administrative data are recognised internationally and by the Australian Government through the National Collaborative Research Infrastructure Strategy Roadmap, which outlined a multi-million dollar investment strategy to develop national record linkage capabilities. This led to the establishment of the Population Health Research Network (PHRN) to coordinate and champion this initiative. The purpose of the PHRN was to establish record linkage units in all Australian states, to support the implementation of secure data delivery and remote access laboratories for researchers, and to develop the Centre for Data Linkage for the linkage of national and cross-jurisdictional data. The Centre for Data Linkage has been established within Curtin University in Western Australia; it provides essential record linkage infrastructure necessary for large-scale, cross-jurisdictional linkage of health related data in Australia and uses a best practice ‘separation principle’ to support data privacy and security. Privacy preserving record linkage technology is also being developed to link records without the use of names to overcome important legal and privacy constraint. This paper will present the findings of the first ‘Proof of Concept’ project selected to demonstrate the effectiveness of increased record linkage capacity in supporting nationally significant health research. This project explored how cross-jurisdictional linkage can inform the nature and extent of cross-border hospital use and hospital-related deaths. The technical challenges associated with national record linkage, and the extent of cross-border population movements, were explored as part of this pioneering research project. Access to person-level data linked across jurisdictions identified geographical hot spots of cross border hospital use and hospital-related deaths in Australia. This has implications for planning of health service delivery and for longitudinal follow-up studies, particularly those involving mobile populations.

Keywords: data integration, data linkage, health planning, health services research

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Authors: Sthanu Mahadev, Wen Chan, Melanie Lim

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Anisotropy dominated continuous-fiber composite materials have garnered attention in numerous mechanical and aerospace structural applications. Tailored mechanical properties in advanced composites can exhibit superiority in terms of stiffness-to-weight ratio, strength-to-weight ratio, low-density characteristics, coupled with significant improvements in fatigue resistance as opposed to metal structure counterparts. Extensive research has demonstrated their core potential as more than just mere lightweight substitutes to conventional materials. Prior work done by Mahadev and Chan focused on formulating a modified composite shell theory based prognosis methodology for investigating the structural response of thin-walled circular cylindrical shell type composite configurations under in-plane mechanical loads respectively. The prime motivation to develop this theory stemmed from its capability to generate simple yet accurate closed-form analytical results that can efficiently characterize circular composite shell construction. It showcased the development of a novel mathematical framework to analytically identify the location of the centroid for thin-walled, open cross-section, curved composite shells that were characterized by circumferential arc angle, thickness-to-mean radius ratio, and total laminate thickness. Ply stress variations for curved cylindrical shells were analytically examined under the application of centric tensile and bending loading. This work presents a cost-effective, small-platform experimental methodology by taking advantage of the full-field measurement capability of digital image correlation (DIC) for an accurate assessment of key mechanical parameters such as in-plane mechanical stresses and strains, centroid location etc. Mechanical property measurement of advanced composite materials can become challenging due to their anisotropy and complex failure mechanisms. Full-field displacement measurements are well suited for characterizing the mechanical properties of composite materials because of the complexity of their deformation. This work encompasses the fabrication of a set of curved cylindrical shell coupons, the design and development of a novel test-fixture design and an innovative experimental methodology that demonstrates the capability to very accurately predict the location of centroid in such curved composite cylindrical strips via employing a DIC based strain measurement technique. Error percentage difference between experimental centroid measurements and previously estimated analytical centroid results are observed to be in good agreement. The developed analytical modified-shell theory provides the capability to understand the fundamental behavior of thin-walled cylindrical shells and offers the potential to generate novel avenues to understand the physics of such structures at a laminate level.

Keywords: anisotropy, composites, curved cylindrical shells, digital image correlation

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Authors: Igor A. Krichtafovitch

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The evolutionary processes are not linear. Long periods of quiet and slow development turn to rather rapid emergences of new species and even phyla. During Cambrian explosion, 22 new phyla were added to the previously existed 3 phyla. Contrary to the common credence the natural selection or a survival of the fittest cannot be accounted for the dominant evolution vector which is steady and accelerated advent of more complex and more intelligent living organisms. Neither Darwinism nor alternative concepts including panspermia and intelligent design propose a satisfactory solution for these phenomena. The proposed hypothesis offers a logical and plausible explanation of the evolutionary processes in general. It is based on two postulates: a) the Biosphere is a single living organism, all parts of which are interconnected, and b) the Biosphere acts as a giant biological supercomputer, storing and processing the information in digital and analog forms. Such supercomputer surpasses all human-made computers by many orders of magnitude. Living organisms are the product of intelligent creative action of the biosphere supercomputer. The biological evolution is driven by growing amount of information stored in the living organisms and increasing complexity of the biosphere as a single organism. Main evolutionary vector is not a survival of the fittest but an accelerated growth of the computational complexity of the living organisms. The following postulates may summarize the proposed hypothesis: biological evolution as a natural life origin and development is a reality. Evolution is a coordinated and controlled process. One of evolution’s main development vectors is a growing computational complexity of the living organisms and the biosphere’s intelligence. The intelligent matter which conducts and controls global evolution is a gigantic bio-computer combining all living organisms on Earth. The information is acting like a software stored in and controlled by the biosphere. Random mutations trigger this software, as is stipulated by Darwinian Evolution Theories, and it is further stimulated by the growing demand for the Biosphere’s global memory storage and computational complexity. Greater memory volume requires a greater number and more intellectually advanced organisms for storing and handling it. More intricate organisms require the greater computational complexity of biosphere in order to keep control over the living world. This is an endless recursive endeavor with accelerated evolutionary dynamic. New species emerge when two conditions are met: a) crucial environmental changes occur and/or global memory storage volume comes to its limit and b) biosphere computational complexity reaches critical mass capable of producing more advanced creatures. The hypothesis presented here is a naturalistic concept of life creation and evolution. The hypothesis logically resolves many puzzling problems with the current state evolution theory such as speciation, as a result of GM purposeful design, evolution development vector, as a need for growing global intelligence, punctuated equilibrium, happening when two above conditions a) and b) are met, the Cambrian explosion, mass extinctions, happening when more intelligent species should replace outdated creatures.

Keywords: supercomputer, biological evolution, Darwinism, speciation

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Authors: Sara Parker, Kay Standing

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This paper will share insights into how menstruators bodies in Nepal are viewed and controlled in Nepal due to the deeply held stigmas and taboos that exist that frame menstrual blood as impure and polluting. It draws on a British Academy Global Challenges Research (BA/GCRF) funded project, ‘Dignity Without Danger,’ that ran from December 2019 to 2022. In Nepal, beliefs and myths around menstrual related practices prevail and vary in accordance to time, generation, caste and class. Physical seclusion and/or restrictions include the consumption of certain foods, the ability to touch certain people and objects, and restricted access to water sources. These restrictions not only put women at risk of poor health outcomes, but they also promote discrimination and challenge fundamental human rights. Despite the pandemic, a wealth of field research and creative outputs have been generated to help break the silence that surrounds menstruation and also highlights the complexity of addressing the harms associated with the exclusion from sacred and profane spaces that menstruators face. Working with locally recruited female research assistants, NGOS and brining together academics from the UK and Nepal, we explore the intersecting factors that impact on menstrual experiences and how they vary throughout Nepal. WE concur with Tamang that there is no such thing as a ‘Nepali Woman’, and there is no one narrative that captures the experiences of menstruators in Nepal. These deeply held beliefs and practices mean that menstruators are denied their right to a dignified menstruation. By being excluded from public and private spaces, such as temples and religious sites, as well as from kitchens and your own bedroom in your own home, these beliefs impact on individuals in complex and interesting ways. Existing research in Nepal by academics and activists demonstrates current programmes and initiatives do not fully address the misconceptions that underpin the exclusionary practices impacting on sexual and reproductive health, a sense of well being and highlight more work is needed in this area. Research has been conducted in all 7 provinces and through exploring and connecting disparate stories, artefacts and narratives, we will deepen understanding of the complexity of menstrual practices enabling local stakeholders to challenge exclusionary practices. By using creative methods to engage with stakeholders and share our research findings as well as highlighting the wealth of activism in Nepal. We highlight the importance of working with local communities, leaders and cutting across disciplines and agencies to promote menstrual justice and dignity. Our research findings and creative outputs that we share on social media channels such as Dignity Without Danger Facebook, Instagram and you tube stress the value of employing a collaborative action research approach to generate material which helps local people take control of their own narrative and change social relations that lead to harmful practices.

Keywords: menstruation, Nepal, stigma, social norms

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Authors: Marcin Dębowski, Marcin Zieliński, Mirosław Krzemieniewski

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As methane fermentation is a complex series of successive biochemical transformations, its subsequent stages are determined, to a various extent, by physical and chemical factors. A specific state of equilibrium is being settled in the functioning fermentation system between environmental conditions and the rate of biochemical reactions and products of successive transformations. In the case of physical factors that influence the effectiveness of methane fermentation transformations, the key significance is ascribed to temperature and intensity of biomass agitation. Among the chemical factors, significant are pH value, type, and availability of the culture medium (to put it simply: the C/N ratio) as well as the presence of toxic substances. One of the important elements which influence the effectiveness of methane fermentation is the pre-treatment of organic substrates and the mode in which the organic matter is made available to anaerobes. Out of all known and described methods for organic substrate pre-treatment before methane fermentation process, the ultrasound disintegration is one of the most interesting technologies. Investigations undertaken on the ultrasound field and the use of installations operating on the existing systems result principally from very wide and universal technological possibilities offered by the sonication process. This physical factor may induce deep physicochemical changes in ultrasonicated substrates that are highly beneficial from the viewpoint of methane fermentation processes. In this case, special role is ascribed to disintegration of biomass that is further subjected to methane fermentation. Once cell walls are damaged, cytoplasm and cellular enzymes are released. The released substances – either in dissolved or colloidal form – are immediately available to anaerobic bacteria for biodegradation. To ensure the maximal release of organic matter from dead biomass cells, disintegration processes are aimed to achieve particle size below 50 μm. It has been demonstrated in many research works and in systems operating in the technical scale that immediately after substrate supersonication the content of organic matter (characterized by COD, BOD5 and TOC indices) was increasing in the dissolved phase of sedimentation water. This phenomenon points to the immediate sonolysis of solid substances contained in the biomass and to the release of cell material, and consequently to the intensification of the hydrolytic phase of fermentation. It results in a significant reduction of fermentation time and increased effectiveness of production of gaseous metabolites of anaerobic bacteria. Because disintegration of Virginia fanpetals biomass via ultrasounds applied in order to intensify its conversion is a novel technique, it is often underestimated by exploiters of agri-biogas works. It has, however, many advantages that have a direct impact on its technological and economical superiority over thus far applied methods of biomass conversion. As for now, ultrasound disintegrators for biomass conversion are not produced on the mass-scale, but by specialized groups in scientific or R&D centers. Therefore, their quality and effectiveness are to a large extent determined by their manufacturers’ knowledge and skills in the fields of acoustics and electronic engineering.

Keywords: ultrasound disintegration, biomass, methane fermentation, biogas, Virginia fanpetals

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Authors: Lara Bettinelli, Bernhard Glatz, Josef Fink

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Planning engineers and researchers use various calculation models with different levels of complexity, calculation efficiency and accuracy in dynamic calculations of railway bridges under high-speed traffic. When choosing a vehicle model to depict the dynamic loading on the bridge structure caused by passing high-speed trains, different goals are pursued: On the one hand, the selected vehicle models should allow the calculation of a bridge’s vibrations as realistic as possible. On the other hand, the computational efficiency and manageability of the models should be preferably high to enable a wide range of applications. The commonly adopted and straightforward vehicle model is the moving load model (MLM), which simplifies the train to a sequence of static axle loads moving at a constant speed over the structure. However, the MLM can significantly overestimate the structure vibrations, especially when resonance events occur. More complex vehicle models, which depict the train as a system of oscillating and coupled masses, can reproduce the interaction dynamics between the vehicle and the bridge superstructure to some extent and enable the calculation of more realistic bridge accelerations. At the same time, such multi-body models require significantly greater processing capacities and precise knowledge of various vehicle properties. The European standards allow for applying the so-called additional damping method when simple load models, such as the MLM, are used in dynamic calculations. An additional damping factor depending on the bridge span, which should take into account the vibration-reducing benefits of the vehicle-bridge interaction, is assigned to the supporting structure in the calculations. However, numerous studies show that when the current standard specifications are applied, the calculation results for the bridge accelerations are in many cases still too high compared to the measured bridge accelerations, while in other cases, they are not on the safe side. A proposal to calculate the additional damping based on extensive dynamic calculations for a parametric field of simply supported bridges with a ballasted track was developed to address this issue. In this contribution, several different approaches to determine the additional damping of the supporting structure considering the vehicle-bridge interaction when using the MLM are compared with one another. Besides the standard specifications, this includes the approach mentioned above and two additional recently published alternative formulations derived from analytical approaches. For a bridge catalogue of 65 existing bridges in Austria in steel, concrete or composite construction, calculations are carried out with the MLM for two different high-speed trains and the different approaches for additional damping. The results are compared with the calculation results obtained by applying a more sophisticated multi-body model of the trains used. The evaluation and comparison of the results allow assessing the benefits of different calculation concepts for the additional damping regarding their accuracy and possible applications. The evaluation shows that by applying one of the recently published redesigned additional damping methods, the calculation results can reflect the influence of the vehicle-bridge interaction on the design-relevant structural accelerations considerably more reliable than by using normative specifications.

Keywords: Additional Damping Method, Bridge Dynamics, High-Speed Railway Traffic, Vehicle-Bridge-Interaction

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Authors: A. Abubakar, A. Parsa, S. Walker

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Despite advances made in the diagnosis and management of drug-sensitive tuberculosis (TB) over the past decades, treatment of multidrug-resistant tuberculosis (MDR-TB) remains challenging and complex particularly in high burden countries including Nigeria. Treatment of MDR-TB is cost-prohibitive with success rate generally lower compared to drug-sensitive TB and if care is not taken it may become the dominant form of TB in future with many treatment uncertainties and substantial morbidity and mortality. Addressing these challenges requires collaborative efforts thorough sustained researches to evaluate the current treatment guidelines, particularly in high burden countries and prevent progression of resistance. To our best knowledge, there has been no research exploring the acceptability, effectiveness, and cost-effectiveness of community-based-MDR-TB treatment model in Nigeria, which is among the high burden countries. The previous similar qualitative study looks at the home-based management of MDR-TB in rural Uganda. This research aimed to explore patient’s views and acceptability of community-based-MDR-TB treatment model and to evaluate and compare the effectiveness and cost-effectiveness of community-based versus hospital-based MDR-TB treatment model of care from the Nigerian perspective. Knowledge of patient’s views and acceptability of community-based-MDR-TB treatment approach would help in designing future treatment recommendations and in health policymaking. Accordingly, knowledge of effectiveness and cost-effectiveness are part of the evidence needed to inform a decision about whether and how to scale up MDR-TB treatment, particularly in a poor resource setting with limited knowledge of TB. Mixed methods using qualitative and quantitative approach were employed. Qualitative data were obtained using in-depth semi-structured interviews with 21 MDR-TB patients in Nigeria to explore their views and acceptability of community-based MDR-TB treatment model. Qualitative data collection followed an iterative process which allowed adaptation of topic guides until data saturation. In-depth interviews were analyzed using thematic analysis. Quantitative data on treatment outcomes were obtained from medical records of MDR-TB patients to determine the effectiveness and direct and indirect costs were obtained from the patients using validated questionnaire and health system costs from the donor agencies to determine the cost-effectiveness difference between community and hospital-based model from the Nigerian perspective. Findings: Some themes have emerged from the patient’s perspectives indicating preference and high acceptability of community-based-MDR-TB treatment model by the patients and mixed feelings about the risk of MDR-TB transmission within the community due to poor infection control. The result of the modeling from the quantitative data is still on course. Community-based MDR-TB care was seen as the acceptable and most preferred model of care by the majority of the participants because of its convenience which in turn enhanced recovery, enables social interaction and offer more psychosocial benefits as well as averted productivity loss. However, there is a need to strengthen this model of care thorough enhanced strategies that ensure guidelines compliance and infection control in order to prevent the progression of resistance and curtail community transmission.

Keywords: acceptability, cost-effectiveness, multidrug-resistant TB treatment, community and hospital approach

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Authors: B. Sudhakara Reddy

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This study provides a snapshot of the sustainability of selected Indian cities by employing 70 indicators in four dimensions to develop an overall city sustainability index. In recent years, the concept of ‘urban sustainability’ has become prominent due to its complexity. Urban areas propel growth and at the same time poses a lot of ecological, social and infrastructural problems and risks. In case of developing countries, the high population density of and the continuous in-migration run the highest risk in natural and man-made disasters. These issues combined with the inability of policy makers in providing basic services makes the cities unsustainable. To assess whether any given policy is moving towards or against urban sustainability it is necessary to consider the relationships among its various dimensions. Hence, in recent years, while preparing the sustainability index, an integral approach involving indicators of different dimensions such as ‘economic’, ‘environmental’ and 'social' is being used. It is also important for urban planners, social analysts and other related institutions to identify and understand the relationships in this complex system. The objective of the paper is to develop a city performance index (CPI) to measure and evaluate the urban regions in terms of sustainable performances. The objectives include: i) Objective assessment of a city’s performance, ii) setting achievable goals iii) prioritise relevant indicators for improvement, iv) learning from leaders, iv) assessment of the effectiveness of programmes that results in achieving high indicator values, v) Strengthening of stakeholder participation. Using the benchmark approach, a conceptual framework is developed for evaluating 25 Indian cities. We develop City Sustainability index (CSI) in order to rank cities according to their level of sustainability. The CSI is composed of four dimensions: Economic, Environment, Social, and Institutional. Each dimension is further composed of multiple indicators: (1) Economic that considers growth, access to electricity, and telephone availability; (2) environmental that includes waste water treatment, carbon emissions, (3) social that includes, equity, infant mortality, and 4) institutional that includes, voting share of population, urban regeneration policies. The CSI, consisting of four dimensions disaggregate into 12 categories and ultimately into 70 indicators. The data are obtained from public and non-governmental organizations, and also from city officials and experts. By ranking a sample of diverse cities on a set of specific dimensions the study can serve as a baseline of current conditions and a marker for referencing future results. The benchmarks and indices presented in the study provide a unique resource for the government and the city authorities to learn about the positive and negative attributes of a city and prepare plans for a sustainable urban development. As a result of our conceptual framework, the set of criteria we suggest is somewhat different to any already in the literature. The scope of our analysis is intended to be broad. Although illustrated with specific examples, it should be apparent that the principles identified are relevant to any monitoring that is used to inform decisions involving decision variables. These indicators are policy-relevant and, hence they are useful tool for decision-makers and researchers.

Keywords: benchmark, city, indicator, performance, sustainability

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Authors: Rizwana Tabassum

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Introductive Statement: Delay in budget releases is often cited as one of the biggest bottlenecks to smooth and efficient service delivery. While budget release from the ministry of finance to the line ministries has been expedited by simplifying the procedure, budget distribution within the line ministries remains one of the major causes of slow budget utilization. While the budget preparation is a bottom-up process where all DDOs submit their proposals to their controlling officers (such as Upazila Civil Surgeon sends it to Director General Health), who consolidate the budget proposals in iBAS++ budget preparation module, the approved budget is not disaggregated by all DDOs. Instead, it is left to the discretion of the controlling officers to distribute the approved budget to their sub-ordinate offices over the course of the year. Though there are some need-based criteria/formulae to distribute the approved budget among DDOs in some sectors, there is little evidence that these criteria are actually used. This means that majority of the DDOs don’t know their yearly allocations upfront to enable yearly planning of activities and expenditures. This delays the implementation of critical activities and the payment to the suppliers of goods and services and sometimes leads to undocumented arrears to suppliers for essential goods/services. In addition, social sector budgets are fragmented because of the vertical programs and externally financed interventions that pose several management challenges at the level of the budget holders and frontline service providers. Slow procurement processes further delay the provision of necessary goods and services. For example, it takes an average of 15–18 months for drugs to reach the Upazila Health Complex and below, while it should not take more than 9 months in procuring and distributing these. Aim of the Study: This paper aims to investigate the budget distribution practices of an emerging economy, Bangladesh. The paper identifies challenges of timely distribution and ways to deal with problems as well. Methodology: The study draws conclusions on the basis of document analysis which is a branch of the qualitative research method. Major Findings: Upon approval of the National Budget, the Ministry of Finance is required to distribute the budget to budget holders at the department level; however, budget is distributed to drawing and disbursing officers much later. Conclusions: Timely and predictable budget releases assist completion of development schemes on time and on budget, with sufficient recurrent resources for effective operation. ADP implementation is usually very low at the beginning of the fiscal year and expedited dramatically during the last few months, leading to inefficient use of resources. The timely budget release will resolve this issue and deliver economic benefits faster, better, and more reliably. This will also give the project directors/DDOs the freedom to think and plan the budget execution in a predictable manner, thereby ensuring value for money by reducing time overrun and expediting the completion of capital investments, and improving infrastructure utilization through timely payment of recurrent costs.

Keywords: budget distribution, challenges, digitization, emerging economy, service delivery

Procedia PDF Downloads 55

Authors: Rafael Carlos C. Aniceto, Bryce Abraham M. Anos, Don Christian A. Cornel, Marjerie Brianna S. Go, Samantha Nicole U. Roque, Earl Christian C. Te

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Indigenous peoples (IPs) in the Philippines are a vulnerable, marginalized group in terms of health and overall well-being due to social inequities and cultural differences. National standards regarding maternal healthcare are geared towards facility-based delivery with modern medicine, health services, and skilled birth attendants. Standards and procedures of care for pregnant mothers do not take into account cultural differences between indigenous people and the majority of the population. There do exist, however, numerous other factors that cause relatively poorer health outcomes among indigenous peoples (IPs). This analytic cross-sectional study sought to determine the association between social determinants of health (SDH), focusing on status as indigenous peoples, and maternal health-related knowledge and attitudes (KA), and health behavior of the Dumagat-Agta indigenous people of Barangay Catablingan and Barangay San Marcelino, General Nakar, Quezon Province, and their utilization of health facilities for antenatal care, facility-based delivery and postpartum care, which would affect their health outcomes (that were not within the scope of this study). To quantitatively measure the primary/secondary exposures and outcomes, a total of 90 face-to-face interviews with IP and non-IP mothers were done. For qualitative information, participant observation among 6 communities (5 IP and 1 non-IP), 11 key informant interviews (traditional and modern health providers) and 4 focused group discussions among IP mothers were conducted. Primary quantitative analyses included chi-squared, T-test and binary logistic regression, while secondary qualitative analyses involved thematic analysis and triangulation. The researchers spent a total of 15 days in the community to learn the culture and participate in the practices of the Dumagat-Agta more intensively and deeply. Overall, utilization of all MNCHN services measured in the study was lower for IP mothers compared to their non-IP counterparts. After controlling for confounders measured in the study, IP status (primary exposure) was found to be significantly correlated with utilization of and adherence to two MNCHN-prescribed services: number of antenatal care check-ups and place of delivery (secondary outcomes). Findings show that being an indigenous mother leads to unfavorable social determinants of health, and if compounded by a difference in knowledge and attitudes, would then lead to poor levels of utilization of MNCHN-prescribed services. Key themes from qualitative analyses show that factors that affected utilization were: culture, land alienation, social discrimination, socioeconomic status, and relations between IPs and non-IPs, specifically with non-IP healthcare providers. The findings of this study aim to be used to help and guide in policy-making, to provide healthcare that is not only adequate and of quality, but more importantly, that addresses inequities stemming from various social determinants, and which is socio-culturally acceptable to indigenous communities. To address the root causes of health problems of IPs, there must be full recognition and exercise of their collective rights to communal assets, specifically land, and self-determination. This would improve maternal and child health outcomes to one of the most vulnerable and neglected sectors in society today.

Keywords: child health, indigenous people, knowledge-attitudes-practices, maternal health, social determinants of health

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Authors: Rajinder Kumar Gupta, Rajni Kant Agrawal, Jaganniwas

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One of the most frightening phenomena of nature is the occurrence of earthquake as it has terrible and disastrous effects. Many earthquakes occur every day worldwide. There is need to have knowledge regarding the trends in earthquake occurrence worldwide. The recoding and interpretation of data obtained from the establishment of the worldwide system of seismological stations made this possible. From the analysis of recorded earthquake data, the earthquake parameters and source parameters can be computed and the earthquake catalogues can be prepared. These catalogues provide information on origin, time, epicenter locations (in term of latitude and longitudes) focal depths, magnitude and other related details of the recorded earthquakes. Theses catalogues are used for seismic hazard estimation. Manual interpretation and analysis of these data is tedious and time consuming. A geographical information system is a computer based system designed to store, analyzes and display geographic information. The implementation of integrated GIS technology provides an approach which permits rapid evaluation of complex inventor database under a variety of earthquake scenario and allows the user to interactively view results almost immediately. GIS technology provides a powerful tool for displaying outputs and permit to users to see graphical distribution of impacts of different earthquake scenarios and assumptions. An endeavor has been made in present study to compile the earthquake data for the whole world in visual Basic on ARC GIS Plate form so that it can be used easily for further analysis to be carried out by earthquake engineers. The basic data on time of occurrence, location and size of earthquake has been compiled for further querying based on various parameters. A preliminary analysis tool is also provided in the user interface to interpret the earthquake recurrence in region. The user interface also includes the seismic hazard information already worked out under GHSAP program. The seismic hazard in terms of probability of exceedance in definite return periods is provided for the world. The seismic zones of the Indian region are included in the user interface from IS 1893-2002 code on earthquake resistant design of buildings. The City wise satellite images has been inserted in Map and based on actual data the following information could be extracted in real time: • Analysis of soil parameters and its effect • Microzonation information • Seismic hazard and strong ground motion • Soil liquefaction and its effect in surrounding area • Impacts of liquefaction on buildings and infrastructure • Occurrence of earthquake in future and effect on existing soil • Propagation of earth vibration due of occurrence of Earthquake GIS based earthquake information system has been prepared for whole world in Visual Basic on ARC GIS Plate form and further extended micro level based on actual soil parameters. Individual tools has been developed for liquefaction, earthquake frequency etc. All information could be used for development of infrastructure i.e. multi story structure, Irrigation Dam & Its components, Hydro-power etc in real time for present and future.

Keywords: GIS based earthquake information system, microzonation, analysis and real time information about liquefaction, infrastructure development

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Authors: Yusuf Hesham Mohamed

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Introduction: Three-dimensional printing technology includes multiple procedures that fabricate three-dimensional objects through consecutively layering two-dimensional cross-sections on top of each other. 3D bioprinting is a promising field of 3D printing, which fabricates tissues and organs by accurately controlling the proper arrangement of diverse biological components. 3D bioprinting uses software and prints biological materials and their supporting components layer-by-layer on a substrate or in a tissue culture plate to produce complex live tissues and organs. 3D food printing is an emerging field of 3D bioprinting in which the 3D printed products are food products that are cheap, require less effort to produce, and have more desirable traits. The Aim of the Study is the development of an affordable 3D bioprinter by altering a locally made CNC instrument with an open-source platform to suit the 3D bio-printer purposes. Later, we went through applying the prototype in several applications regarding food technology and drug testing, including the organ-On-Chip. Materials and Methods: An off-the-shelf 3D printer was modified by designing and fabricating the syringe unit, which was designed on the basis of the Milli-fluidics system. Sodium alginate and gelatin hydrogels were prepared, followed by leaf cell suspension preparation from narrow sections of Fragaria’s viable leaves. The desired 3D structure was modeled, and 3D printing preparations took place. Cell-free and cell-laden hydrogels were printed at room temperature under sterile conditions. Post printing curing process was performed. The printed structure was further studied. Results: Positive results have been achieved using the altered 3D bioprinter where a 3D hydrogel construct of two layers made of the combination of sodium alginate to gelatin (15%: 0.5%) has been printed. DLP 3D printer was used to design the syringe component with a transparent PLA-Pro resin for the creation of a microfluidics system having two channels altered to the double extruder. The hydrogel extruder’s design was based on peristaltic pumps, which utilized a stepper motor. The design and fabrication were made using DIY-3D printed parts. Hard plastic PLA was the material utilized for printing. SEM was used to carry out the porous 3D construct imaging. Multiple physical and chemical tests were performed in order to ensure that the cell line was suitable for hosting. Fragaria plant was developed by suspending Fragaria’s cells from its leaves using the 3D bioprinter. Conclusion: 3D bioprinting is considered to be an emerging scientific field that can facilitate and improve many scientific tests and studies. Thus, having a 3D bioprinter in labs is considered to be an essential requirement. 3D bioprinters are very expensive; however, the fabrication of a 3D printer into a 3D bioprinter can lower the cost of the bioprinter. The 3D bioprinter implemented made use of peristaltic pumps instead of syringe-based pumps in order to extend the ability to print multiple types of materials and cells.

Keywords: scaffold, eco on chip, 3D bioprinter, DLP printer

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Authors: Rania Raouf Sedky

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Adaptive architecture relates to buildings specifically designed to adapt to their residents and their environments. To design a biologically adaptive system, we can observe how living creatures in nature constantly adapt to different external and internal stimuli to be a great inspiration. The issue is not just how to create a system that is capable of change but also how to find the quality of change and determine the incentive to adapt. The research examines the possibilities of transforming spaces using the human body as an active tool. The research also aims to design and build an effective dynamic structural system that can be applied on an architectural scale and integrate them all into the creation of a new adaptive system that allows us to conceive a new way to design, build and experience architecture in a dynamic manner. The main objective was to address the possibility of a reciprocal transformation between the user and the architectural element so that the architecture can adapt to the user, as the user adapts to architecture. The motivation is the desire to deal with the psychological benefits of an environment that can respond and thus empathize with human emotions through its ability to adapt to the user. Adaptive affiliations of kinematic structures have been discussed in architectural research for more than a decade, and these issues have proven their effectiveness in developing kinematic structures, responsive and adaptive, and their contribution to 'smart architecture'. A wide range of strategies have been used in building complex kinetic and robotic systems mechanisms to achieve convertibility and adaptability in engineering and architecture. One of the main contributions of this research is to explore how the physical environment can change its shape to accommodate different spatial displays based on the movement of the user’s body. The main focus is on the relationship between materials, shape, and interactive control systems. The intention is to develop a scenario where the user can move, and the structure interacts without any physical contact. The soft form of shifting language and interaction control technology will provide new possibilities for enriching human-environmental interactions. How can we imagine a space in which to construct and understand its users through physical gestures, visual expressions, and response accordingly? How can we imagine a space whose interaction depends not only on preprogrammed operations but on real-time feedback from its users? The research also raises some important questions for the future. What would be the appropriate structure to show physical interaction with the dynamic world? This study concludes with a strong belief in the future of responsive motor structures. We imagine that they are developing the current structure and that they will radically change the way spaces are tested. These structures have obvious advantages in terms of energy performance and the ability to adapt to the needs of users. The research highlights the interface between remote sensing and a responsive environment to explore the possibility of an interactive architecture that adapts to and responds to user movements. This study ends with a strong belief in the future of responsive motor structures. We envision that it will improve the current structure and that it will bring a fundamental change to the way in which spaces are tested.

Keywords: adaptive architecture, interactive architecture, responsive architecture, tensegrity

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Authors: Sabrina Neururer, Marco Schweitzer, Werner Hackl, Bernhard Tilg, Patrick Raudaschl, Andreas Huber, Bernhard Pfeifer

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History and the current outbreak of Covid-19 have shown the deadly potential of infectious diseases. However, infectious diseases also have a serious impact on areas other than health and healthcare, such as the economy or social life. These areas are strongly codependent. Therefore, disease control measures, such as social distancing, quarantines, curfews, or lockdowns, have to be adopted in a very considerate manner. Infectious disease modeling can support policy and decision-makers with adequate information regarding the dynamics of the pandemic and therefore assist in planning and enforcing appropriate measures that will prevent the healthcare system from collapsing. In this work, an agent-based simulation package named “survival” for simulating infectious diseases is presented. A special focus is put on SARS-Cov-2. The presented simulation package was used in Austria to model the SARS-Cov-2 outbreak from the beginning of 2020. Agent-based modeling is a relatively recent modeling approach. Since our world is getting more and more complex, the complexity of the underlying systems is also increasing. The development of tools and frameworks and increasing computational power advance the application of agent-based models. For parametrizing the presented model, different data sources, such as known infections, wastewater virus load, blood donor antibodies, circulating virus variants and the used capacity for hospitalization, as well as the availability of medical materials like ventilators, were integrated with a database system and used. The simulation result of the model was used for predicting the dynamics and the possible outcomes and was used by the health authorities to decide on the measures to be taken in order to control the pandemic situation. The survival package was implemented in the programming language Java and the analytics were performed with R Studio. During the first run in March 2020, the simulation showed that without measures other than individual personal behavior and appropriate medication, the death toll would have been about 27 million people worldwide within the first year. The model predicted the hospitalization rates (standard and intensive care) for Tyrol and South Tyrol with an accuracy of about 1.5% average error. They were calculated to provide 10-days forecasts. The state government and the hospitals were provided with the 10-days models to support their decision-making. This ensured that standard care was maintained for as long as possible without restrictions. Furthermore, various measures were estimated and thereafter enforced. Among other things, communities were quarantined based on the calculations while, in accordance with the calculations, the curfews for the entire population were reduced. With this framework, which is used in the national crisis team of the Austrian province of Tyrol, a very accurate model could be created on the federal state level as well as on the district and municipal level, which was able to provide decision-makers with a solid information basis. This framework can be transferred to various infectious diseases and thus can be used as a basis for future monitoring.

Keywords: modelling, simulation, agent-based, SARS-Cov-2, COVID-19

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Authors: Majid Alenezi, Abdelbare Algamode, Amy Hayes, Gavin Lawrence, Nichola Callow

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The purpose of this study was to translate and culturally adapt the Vividness of Movement Imagery Questionnaire-2 (VMIQ-2) from English to produce a new Arabic version (VMIQ-2A), and to evaluate the reliability and validity of the translated questionnaire. The questionnaire assesses how vividly and clearly individuals are able to imagine themselves performing everyday actions. Its purpose is to measure individuals’ ability to conduct movement imagery, which can be defined as “the cognitive rehearsal of a task in the absence of overt physical movement.” Movement imagery has been introduced in physiotherapy as a promising intervention technique, especially when physical exercise is not possible (e.g. pain, immobilisation.) Considerable evidence indicates movement imagery interventions improve physical function, but to maximize efficacy it is important to know the imagery abilities of the individuals being treated. Given the increase in the global sharing of knowledge it is desirable to use standard measures of imagery ability across language and cultures, thus motivating this project. The translation procedure followed guidelines from the Translation and Cultural Adaptation group of the International Society for Pharmacoeconomics and Outcomes Research and involved the following phases: Preparation; the original VMIQ-2 was adapted slightly to provide additional information and simplified grammar. Forward translation; three native speakers resident in Saudi Arabia translated the original VMIQ-2 from English to Arabic, following instruction to preserve meaning (not literal translation), and cultural relevance. Reconciliation; the project manager (first author), the primary translator and a physiotherapist reviewed the three independent translations to produce a reconciled first Arabic draft of VMIQ-2A. Backward translation; a fourth translator (native Arabic speaker fluent in English) translated literally the reconciled first Arabic draft to English. The project manager and two study authors compared the English back translation to the original VMIQ-2 and produced the second Arabic draft. Cognitive debriefing; to assess participants’ understanding of the second Arabic draft, 7 native Arabic speakers resident in the UK completed the questionnaire, and rated the clearness of the questions, specified difficult words or passages, and wrote in their own words their understanding of key terms. Following review of this feedback, a final Arabic version was created. 142 native Arabic speakers completed the questionnaire in community meeting places or at home; a subset of 44 participants completed the questionnaire a second time 1 week later. Results showed the translated questionnaire to be valid and reliable. Correlation coefficients indicated good test-retest reliability. Cronbach’s a indicated high internal consistency. Construct validity was tested in two ways. Imagery ability scores have been found to be invariant across gender; this result was replicated within the current study, assessed by independent-samples t-test. Additionally, experienced sports participants have higher imagery ability than those less experienced; this result was also replicated within the current study, assessed by analysis of variance, supporting construct validity. Results provide preliminary evidence that the VMIQ-2A is reliable and valid to be used with a general population who are native Arabic speakers. Future research will include validation of the VMIQ-2A in a larger sample, and testing validity in specific patient populations.

Keywords: motor imagery, physiotherapy, translation and validation, imagery ability

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Authors: Mokhlisur Rahman

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Ocean inhibits one of the most complex ecosystems on the planet that regulates the earth's climate and weather by providing us with compatible weather to live. Ocean provides food by extending various ways of lifestyles that are dependent on it, transportation by accommodating the world's biggest carriers, recreation by offering its beauty in many moods, and home to countless species. At the essence of receiving various forms of entertainment, consumers choose to be close to the ocean while performing many fun activities. Which, at some point, upsets the stomach of the ocean by threatening marine life and the environment. Consumers throw the waste into the ocean after using it. Most of them are plastics that float over the ocean and turn into thousands of micro pieces that are hard to observe with the naked eye but easily eaten by the sea species. Eventually, that conflicts with the natural consumption process of any living species, making them sick. This information is not known by most consumers who go to the sea or seashores occasionally to spend time, nor is it widely discussed, which creates an information gap among consumers. However, advertising is a powerful tool to educate people about ocean pollution. This abstract analyzes three major ocean-saving advertisement campaigns that use innovative and advanced technology to get maximum exposure. The study collects data from the selected campaigns' websites and retrieves all available content related to messages, videos, and images. First, the SeaLegacy campaign uses stunning images to create awareness among the people; they use social media content, videos, and other educational content. They create content and strategies to build an emotional connection among the consumers that encourage them to move on an action. All the messages in their campaign empower consumers by using powerful words. Second, Ocean Conservancy Campaign uses social media marketing, events, and educational content to protect the ocean from various pollutants, including plastics, climate change, and overfishing. They use powerful images and videos of marine life. Their mission is to create evidence-based solutions toward a healthy ocean. Their message includes the message regarding the local communities along with the sea species. Third, ocean clean-up is a campaign that applies strategies using innovative technologies to remove plastic waste from the ocean. They use social media, digital, and email marketing to reach people and raise awareness. They also use images and videos to evoke an emotional response to take action. These tree advertisements use realistic images, powerful words, and the presence of living species in the imagery presentation, which are eye-catching and can grow emotional connection among the consumers. Identifying the effectiveness of the messages these advertisements carry and their strategies highlights the knowledge gap of mass people between real pollution and its consequences, making the message more accessible to the mass of people. This study aims to provide insights into the effectiveness of ocean-saving advertisement campaigns and their impact on the public's awareness of ocean conservation. The findings from this study help shape future campaigns.

Keywords: advertising-campaign, content-creation, images ocean-saving technology, videos

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Authors: Ho-Ting Wu, Kai-Wei Ke, Bo-Yu Huang, Liang-Lin Yan, Chun-Ting Lin

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With the advances in advanced technology, wireless sensor network (WSN) has become one of the most promising candidates to implement the wireless industrial internet of things (IIOT) architecture. However, the legacy IEEE 802.15.4 based WSN technology such as Zigbee system cannot meet the stringent QoS requirement of low powered, real-time, and highly reliable transmission imposed by the IIOT environment. Recently, the IEEE society developed IEEE 802.15.4e Time Slotted Channel Hopping (TSCH) access mode to serve this purpose. Furthermore, the IETF 6TiSCH working group has proposed standards to integrate IEEE 802.15.4e with IPv6 protocol smoothly to form a complete protocol stack for IIOT. In this work, we develop key network technologies for IEEE 802.15.4e based wireless IIoT architecture, focusing on practical design and system implementation. We realize the OpenWSN-based wireless IIOT system. The system architecture is divided into three main parts: web server, network manager, and sensor nodes. The web server provides user interface, allowing the user to view the status of sensor nodes and instruct sensor nodes to follow commands via user-friendly browser. The network manager is responsible for the establishment, maintenance, and management of scheduling and topology information. It executes centralized scheduling algorithm, sends the scheduling table to each node, as well as manages the sensing tasks of each device. Sensor nodes complete the assigned tasks and sends the sensed data. Furthermore, to prevent scheduling error due to packet loss, a schedule inspection mechanism is implemented to verify the correctness of the schedule table. In addition, when network topology changes, the system will act to generate a new schedule table based on the changed topology for ensuring the proper operation of the system. To enhance the system performance of such system, we further propose dynamic bandwidth allocation and distributed scheduling mechanisms. The developed distributed scheduling mechanism enables each individual sensor node to build, maintain and manage the dedicated link bandwidth with its parent and children nodes based on locally observed information by exchanging the Add/Delete commands via two processes. The first process, termed as the schedule initialization process, allows each sensor node pair to identify the available idle slots to allocate the basic dedicated transmission bandwidth. The second process, termed as the schedule adjustment process, enables each sensor node pair to adjust their allocated bandwidth dynamically according to the measured traffic loading. Such technology can sufficiently satisfy the dynamic bandwidth requirement in the frequently changing environments. Last but not least, we propose a packet retransmission scheme to enhance the system performance of the centralized scheduling algorithm when the packet delivery rate (PDR) is low. We propose a multi-frame retransmission mechanism to allow every single network node to resend each packet for at least the predefined number of times. The multi frame architecture is built according to the number of layers of the network topology. Performance results via simulation reveal that such retransmission scheme is able to provide sufficient high transmission reliability while maintaining low packet transmission latency. Therefore, the QoS requirement of IIoT can be achieved.

Keywords: IEEE 802.15.4e, industrial internet of things (IIOT), scheduling mechanisms, wireless sensor networks (WSN)

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Authors: Emma J. Dale, Christina D. Buesching, Kevin R. Theis, David W. Macdonald

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This study investigates the oral and intestinal microbiomes of wild-living European badgers (Meles meles) and will relate inter-individual differences to social contact networks, somatic and reproductive fitness, varying susceptibility to bovine tuberculous (bTB) and to the olfactory advertisement. Badgers are an interesting model for this research, as they have great variation in body condition, despite living in complex social networks and having access to the same resources. This variation in somatic fitness, in turn, affects breeding success, particularly in females. We postulate that microbiota have a central role to play in determining the successfulness of an individual. Our preliminary results, characterising the microbiota of individual badgers, indicate unique compositions of microbiota communities within social groups of badgers. This basal information will inform further questions related to the extent microbiota influence fitness. Hitherto, the potential role of microbiota has not been considered in determining host condition, but also other key fitness variables, namely; communication and resistance to disease. Badgers deposit their faeces in communal latrines, which play an important role in olfactory communication. Odour profiles of anal and subcaudal gland secretions are highly individual-specific and encode information about group-membership and fitness-relevant parameters, and their chemical composition is strongly dependent on symbiotic microbiota. As badgers sniff/ lick (using their Vomeronasal organ) and over-mark faecal deposits of conspecifics, these microbial communities can be expected to vary with social contact networks. However, this is particularly important in the context of bTB, where badgers are assumed to transmit bTB to cattle as well as conspecifics. Interestingly, we have found that some individuals are more susceptible to bTB than are others. As acquired immunity and thus potential susceptibility to infectious diseases are known to depend also on symbiotic microbiota in other members of the mustelids, a role of particularly oral microbiota can currently not be ruled out as a potential explanation for inter-individual differences in infection susceptibility of bTB in badgers. Tri annually badgers are caught in the context of a long-term population study that began in 1987. As all badgers receive an individual tattoo upon first capture, age, natal as well as previous and current social group-membership and other life history parameters are known for all animals. Swabs (subcaudal ‘scent gland’, anal, genital, nose, mouth and ear) and fecal samples will be taken from all individuals, stored at -80oC until processing. Microbial samples will be processed and identified at Wayne State University’s Theis (Host-Microbe Interactions) Lab, using High Throughput Sequencing (16S rRNA-encoding gene amplification and sequencing). Acknowledgments: Gas-Chromatography/ Mass-spectrometry (in the context of olfactory communication) analyses will be performed through an established collaboration with Dr. Veronica Tinnesand at Telemark University, Norway.

Keywords: communication, energetics, fitness, free-ranging animals, immunology

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Authors: Meinrad Haule Lembuka

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Introduction: Ubuntu culture represents African humanism with collective and positive feeling of people living together, interdependence, equally and peaceful etc. Overtime, Ubuntu culture developed varieties of communicative strategies to express experiences, feelings and knowledge. Khanga or kanga (garment) is among the Ubuntu cultural practice of Bantu speaking people along the East African coast following interaction with Arabs and Bantu speaking people to formulate Swahili culture. Kanga or Kanga is a Swahili word which means a traditional soft cotton cloths in varieties of colours, patterns, and styles which as a deep cultural, historical, and social significance not only in Tanzania but the rest of East African coast. Swahili culture is a sub culture of Ubuntu African culture which is rich in customs and rituals that serve to preserve goodness and life where Tanzania, like the rest of East African societies along the Indian coast engaged in kanga dressing custom under Swahili culture to express their feelings and knowledge sharing. After the independence of Tanzania (formerly Tanganyika) from British colonial rule, Kanga traditional dressing gained momentum in Swahili culture and spread to the rest of East Africa and beyond. To date kanga dressing holds a good position as a formal and informal tool for advocating marginalised groups, counselling, psychosocial therapy, liberation, compassion, love, justice, campaign, and cerebration etc. Methodology: A literature review method was guided by Ubuntu theory to assess the implications of kanga traditional dressing in empowering Tanzanian community. Findings: During slavery, slaves wore Kaniki and people despised Kaniki dressing due to its association with slavery. Ex-slave women seeking to become part of the Swahili society began to decorate their Kaniki clothes. After slavery was abolished in 1897, Kangas began to be used for self-empowerment and to indicate that the wearer had personal wealth. During colonial era, freedom of expressions for Africans were restricted by colonial masters thus Tanzanians used kanga to express the evils of colonialism and other social problems, Under Ubuntu value of unity and solidarity liberation and independence fighters crafted motto and liberation messages that were shared and spread rapidly in the community. Political parities like TANU used kanga to spread nationalism and Ujamaa policy. kanga is more than a piece of fabric-it is a space for women to voice unspeakable communication and a women-centred repository for indigenous knowledge, feminisms addressing social ills, happiness, campaigns, memories and reconciliation etc. Kanga provides an indirect voice and support vulnerable and marginalised populations and strongly it has proved to be a peaceful platform of capture attention of government and societies. Kanga textiles gained increased international fame when an Obama kanga design was produced upon the president’s election in 2008 and his visit to Tanzania in 2013. Conclusion: Kanga preserves and symbolises Swahili culture and contributes in realization of social justice, inclusion, national identity and unity. As an inclusive cultural tool, Kanga spread across Africa to international community and the practice has moved from being a woman domination dressing code to other sex orientations.

Keywords: African culture, Kanga, khanga, swahili culture, ubuntu

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Authors: Tatsiana Ihnatovich, Darya Nizheharodava, Mikalai Halabarodzka, Tatsiana Savitskaya, Marina Zafranskaya

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Liver fibrosis is a complex of histological changes resulting from chronic liver disease accompanied by an excessive production and deposition of extracellular matrix components in the hepatic parenchyma. Liver fibrosis is a serious medical and social problem. Hepatic stellate cells (HSCs) make a significant contribution to the extracellular matrix deposition due to liver injury. Mesenchymal stem cells (MSCs) have a pronounced anti-inflammatory, regenerative and immunomodulatory effect; they are able to differentiate into hepatocytes and induce apoptosis of activated HSCs that opens the prospect of their use for preventing the excessive fibro-formation and the development of liver cirrhosis. The aim of the study is to evaluate the effect of MSCs therapy on the expression of fibrogenesis markers genes in liver tissue and HSCs cultures of rats with experimental liver cirrhosis (ELC). Materials and methods: ELC was induced by the common bile duct ligation (CBDL) in female Wistar rats (n = 19) with an average body weight of 250 (220 ÷ 270) g. Animals from the control group (n = 10) were sham-operated. On the 56th day after the CBDL, the rats of the experimental (n = 12) and the control (n = 5) groups received intraportal MSCs in concentration of 1×106 cells/animal (previously obtained from rat’s bone marrow) or saline, respectively. The animals were taken out of the experiment on the 21st day. HSCs were isolated by sequential liver perfusion in situ with following disaggregation, enzymatic treatment and centrifugation of cell suspension on a two-stage density gradient. The expression of collagen type I (Col1a1) and type III (Col3a1), matrix metalloproteinase type 2 (MMP2) and type 9 (MMP9), tissue inhibitor of matrix metalloproteinases type 1 (TIMP1), transforming growth factor β type 1 (TGFβ1) and type 3 (TGFβ3) was determined by real-time polymerase chain reaction. Statistical analysis was performed using Statistica 10.0. Results: In ELC rats compared to sham-operated animals, a significant increase of all studied markers expression was observed. The administration of MSCs led to a significant decrease of all detectable markers in the experimental group compared to rats without cell therapy. In ELC rats, an increased MMP9/TIMP1 ratio after cell therapy was also detected. The infusion of MSCs in the sham-operated animals did not lead to any changes. In the HSCs from ELC animals, the expression of Col1a1 and Col3a1 exceeded the similar parameters of the control group (p <0.05) and statistically decreased after the MSCs administration. The correlation between Col3a1 (Rs = 0.51, p <0.05), TGFβ1 (Rs = 0.6, p <0.01), and TGFβ3 (Rs = 0.75, p <0.001) expression in HSCs cultures and liver tissue has been found. Conclusion: Intraportal administration of MSCs to rats with ELC leads to a decreased Col1a1 and Col3a1, MMP2 and MMP9, TIMP1, TGFβ1 and TGFβ3 expression. The correlation between the expression of Col3a1, TGFβ1 and TGFβ3 in liver tissue and in HSCs cultures indicates the involvement of activated HSCs in the fibrogenesis that allows considering HSCs to be the main cell therapy target in ELC.

Keywords: cell therapy, experimental liver cirrhosis, hepatic stellate cells, mesenchymal stem cells

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Authors: Babatunde Kolawole

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This paper embarks on an exploration of the compelling interplay between documentary filmmaking and activism, delving into their symbiotic relationship and profound impact on advocacy and social justice causes. Through an in-depth analysis of diverse case studies, it seeks to illuminate the instances where documentary films have emerged as potent tools for effecting social change and advancing the principles of justice. This research underscores the vital role played by documentary filmmakers in harnessing the medium's unique capacity to engage, educate, and mobilize audiences while advocating for societal transformation. The primary focus of this study is on a selection of compelling case studies spanning various topics and causes, each exemplifying the marriage between documentary filmmaking and activism. These case studies encompass a broad spectrum of subjects, from environmental conservation and climate change to civil rights movements and human rights struggles. By examining these real-world instances, this paper endeavors to provide a comprehensive understanding of the strategies, challenges, and ethical considerations that underpin the practice of documentary filmmaking as a form of activism. Throughout the paper, it becomes evident that the potency of documentary filmmaking lies in its ability to blend artistry with social impact. The selected case studies vividly demonstrate how documentary filmmakers, armed with cameras and a passion for change, have emerged as critical agents of societal transformation. Whether it be exposing environmental atrocities, shedding light on systemic inequalities, or giving voice to marginalized communities, these documentaries have played a pivotal role in pushing the boundaries of advocacy and social justice. One of the key themes explored in this paper is the evolving nature of documentary filmmaking as a tool for activism. It delves into the shift from traditional observational documentaries to more participatory and immersive approaches, highlighting the dynamic ways in which filmmakers engage with their subjects and audiences. This evolution is exemplified in case studies where filmmakers have collaborated with the communities they document, fostering a sense of agency and empowerment among those whose stories are being told. Furthermore, this research underscores the ethical considerations inherent in the intersection of documentary filmmaking and activism. It scrutinizes questions surrounding representation, objectivity, and the responsibility of filmmakers in portraying complex social issues. By dissecting ethical dilemmas faced by documentary filmmakers in these case studies, this paper encourages a critical examination of the ethical boundaries and obligations in the realm of advocacy-driven filmmaking. In conclusion, this paper aims to shed light on the remarkable potential of documentary filmmaking as a catalyst for activism and social justice. Through the lens of compelling case studies, it illustrates the transformative power of the medium in effecting change, amplifying underrepresented voices, and mobilizing global audiences. It is hoped that this research will not only inform the discourse on documentary activism but also inspire filmmakers, scholars, and advocates to continue leveraging the cinematic art form as a formidable force for a more just and equitable world.

Keywords: film, filmmaker, documentary, human right

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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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