Search results for: inflammatory hypothesis of psychosis
Commenced in January 2007
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Paper Count: 2230

Search results for: inflammatory hypothesis of psychosis

190 Code-Switching as a Bilingual Phenomenon among Students in Prishtina International Schools

Authors: Festa Shabani

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This paper aims at investigating bilingual speech in the International Schools of Prishtina. More particularly, it seeks to analyze bilingual phenomena among adolescent students highly exposed to English with the latter as the language of instruction at school in naturally-occurring conversations within school environment. Adolescence was deliberately chosen since it is regarded as an age when peer influence on language choice is the greatest. Driven by daily unsystematic observation and prior research already undertaken, the hypothesis stated is that Albanian continues to be the dominant language among Prishtina international schools’ students with a lot of code-switched items from the English. Furthermore, they will also use lexical borrowings - words already adapted in the receiving language, from the language they have been in contact with, in their speech often in the lack of existing equivalents in Albanian or for other reasons. This is done owing to the fact that the language of instruction at school is English, and any topic related to the language they have been exposed to will trigger them to use English. Therefore, this needs special attention in an attempt to identify patterns of their speech; in this way, linguistic and socio-pragmatic factors will be considered when analyzing the motivations behind their language choice. Methodology for collecting data include participant systematic observation and tape-recording. While observing them in their natural conversations, the fieldworker also took notes, which helped transcribe details better. The paper starts by raising the question of whether code-switching is occurring among Prishtina International Schools’ students highly exposed to English. The data gathered from students in informal settings suggests that there are well-founded grounds for an affirmative answer. The participants in this study are observed to be code-switching, although showing differences in degree. However, a generalization cannot be made on the basis of the findings except in so far it appears that English has, in turn, became a language to which they turn when identifying with the group when discussing about particular school topics. Particularly, participants seemed to use intra-sentential CS in cases when they seem to find an English expression rather easier than an Albanian one when repeating or emphasizing a point when urged to talk about educational issues with English being their language of instruction, and inter-sentential code-switching, particularly when quoting others. Concerning the grammatical aspect of code-switching, the intrasentential CS is used more than the intersentetial one. Speaking of gender, the results show that there were really no significant differences in regards quantity between male and female participants. However, the slight tendency for men to code switch intrasententially more than women was manifested. Similarly, a slight tendency again for a difference to emerge is on intersentential switching, which contributes 21% to the total number of switches for women, but 11% to the total number of switches for men.

Keywords: Albanian, code-switching contact linguistics, bilingual phenomena, lexical borrowing, English

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189 Antioxidant Potency of Ethanolic Extracts from Selected Aromatic Plants by in vitro Spectrophotometric Analysis

Authors: Tatjana Kadifkova Panovska, Svetlana Kulevanova, Blagica Jovanova

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Biological systems possess the ability to neutralize the excess of reactive oxygen species (ROS) and to protect cells from destructive alterations. However, many pathological conditions (cardiovascular diseases, autoimmune disorders, cancer) are associated with inflammatory processes that generate an excessive amount of reactive oxygen species (ROS) that shift the balance between endogenous antioxidant systems and free oxygen radicals in favor of the latter, leading to oxidative stress. Therefore, an additional source of natural compounds with antioxidant properties that will reduce the amount of ROS in cells is much needed despite their broad utilization; many plant species remain largely unexplored. Therefore, the purpose of the present study is to investigate the antioxidant activity of twenty-five selected medicinal and aromatic plant species. The antioxidant activity of the ethanol extracts was evaluated with in vitro assays: 2,2’-diphenyl-1-pycryl-hydrazyl (DPPH), ferric reducing antioxidant power (FRAP), non-site-specific- (NSSOH) and site-specific hydroxyl radical-2-deoxy-D-ribose degradation (SSOH) assays. The Folin-Ciocalteu method and AlCl3 method were performed to determine total phenolic content (TPC) and total flavonoid content (TFC). All examined plant extracts manifested antioxidant activity to a different extent. Cinnamomum verum J.Presl bark and Ocimum basilicum L. Herba demonstrated strong radical scavenging activity and reducing power with the DPPH and FRAP assay, respectively. Additionally, significant hydroxyl scavenging potential and metal chelating properties were observed using the NSSOH and SSOH assays. Furthermore, significant variations were determined in the total polyphenolic content (TPC) and total flavonoid content (TFC), with Cinnamomum verum and Ocimum basilicum showing the highest amount of total polyphenols. The considerably strong radical scavenging activity, hydroxyl scavenging potential and reducing power for the species mentioned above suggest of a presence of highly bioactive phytochemical compounds, predominantly polyphenols. Since flavonoids are the most abundant group of polyphenols that possess a large number of available reactive OH groups in their structure, it is considered that they are the main contributors to the radical scavenging properties of the examined plant extracts. This observation is supported by the positive correlation between the radical scavenging activity and the total polyphenolic and flavonoid content obtained in the current research. The observations from the current research nominate Cinnamomum verum bark and Ocimum basilicum herba as potential sources of bioactive compounds that could be utilized as antioxidative additives in the food and pharmaceutical industries. Moreover, the present study will help the researchers as basic data for future research in exploiting the hidden potential of these important plants that have not been explored so far.

Keywords: ethanol extracts, radical scavenging activity, reducing power, total polyphenols.

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188 Phylogenetic Inferences based on Morphoanatomical Characters in Plectranthus esculentus N. E. Br. (Lamiaceae) from Nigeria

Authors: Otuwose E. Agyeno, Adeniyi A. Jayeola, Bashir A. Ajala

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P. esculentus is indigenous to Nigeria yet no wild relation has been encountered or reported. This has made it difficult to establish proper lineages between the varieties and landraces under cultivation. The present work is the first to determine the apormophy of 135 morphoanatomical characters in organs of 46 accessions drawn from 23 populations of this species based on dicta. The character states were coded in accession x character-state matrices and only 83 were informative and utilised for neighbour joining clustering based on euclidean values, and heuristic search in parsimony analysis using PAST ver. 3.15 software. Compatibility and evolutionary trends between accessions were then explored from values and diagrams produced. The low consistency indices (CI) recorded support monophyly and low homoplasy in this taxon. Agglomerative schedules based on character type and source data sets divided the accessions into mainly 3 clades, each of complexes of accessions. Solenostemon rotundifolius (Poir) J.K Morton was the outgroup (OG) used, and it occurred within the largest clades except when the characters were combined in a data set. The OG showed better compatibility with accessions of populations of landrace Isci, and varieties Riyum and Long’at. Otherwise, its aerial parts are more consistent with those of accessions of variety Bebot. The highly polytomous clades produced due to anatomical data set may be an indication of how stable such characters are in this species. Strict consensus trees with more than 60 nodes outputted showed that the basal nodes were strongly supported by 3 to 17 characters across the data sets, suggesting that populations of this species are more alike. The OG was clearly the first diverging lineage and closely related to accessions of landrace Gwe and variety Bebot morphologically, but different from them anatomically. It was also distantly related to landrace Fina and variety Long’at in terms of root, stem and leaf structural attributes. There were at least 5 other clades with each comprising of complexes of accessions from different localities and terrains within the study area. Spherical stem in cross section, size of vascular bundles at the stem corners as well as the alternate and whorl phyllotaxy are attributes which may have facilitated each other’s evolution in all accessions of the landrace Gwe, and they may be innovative since such states are not characteristic of the larger Lamiaceae, and Plectranthus L’Her in particular. In conclusion, this study has provided valuable information about infraspecific diversity in this taxon. It supports recognition of the varietal statuses accorded to populations of P. esculentus, as well as the hypothesis that the wild gene might have been distributed on the Jos Plateau. However, molecular characterisation of accessions of populations of this species would resolve this problem better.

Keywords: clustering, lineage, morphoanatomical characters, Nigeria, phylogenetics, Plectranthus esculentus, population

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187 The Association of Southeast Asian Nations (ASEAN) and the Dynamics of Resistance to Sovereignty Violation: The Case of East Timor (1975-1999)

Authors: Laura Southgate

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The Association of Southeast Asian Nations (ASEAN), as well as much of the scholarship on the organisation, celebrates its ability to uphold the principle of regional autonomy, understood as upholding the norm of non-intervention by external powers in regional affairs. Yet, in practice, this has been repeatedly violated. This dichotomy between rhetoric and practice suggests an interesting avenue for further study. The East Timor crisis (1975-1999) has been selected as a case-study to test the dynamics of ASEAN state resistance to sovereignty violation in two distinct timeframes: Indonesia’s initial invasion of the territory in 1975, and the ensuing humanitarian crisis in 1999 which resulted in a UN-mandated, Australian-led peacekeeping intervention force. These time-periods demonstrate variation on the dependent variable. It is necessary to observe covariation in order to derive observations in support of a causal theory. To establish covariation, my independent variable is therefore a continuous variable characterised by variation in convergence of interest. Change of this variable should change the value of the dependent variable, thus establishing causal direction. This paper investigates the history of ASEAN’s relationship to the norm of non-intervention. It offers an alternative understanding of ASEAN’s history, written in terms of the relationship between a key ASEAN state, which I call a ‘vanguard state’, and selected external powers. This paper will consider when ASEAN resistance to sovereignty violation has succeeded, and when it has failed. It will contend that variation in outcomes associated with vanguard state resistance to sovereignty violation can be best explained by levels of interest convergence between the ASEAN vanguard state and designated external actors. Evidence will be provided to support the hypothesis that in 1999, ASEAN’s failure to resist violations to the sovereignty of Indonesia was a consequence of low interest convergence between Indonesia and the external powers. Conversely, in 1975, ASEAN’s ability to resist violations to the sovereignty of Indonesia was a consequence of high interest convergence between Indonesia and the external powers. As the vanguard state, Indonesia was able to apply pressure on the ASEAN states and obtain unanimous support for Indonesia’s East Timor policy in 1975 and 1999. However, the key factor explaining the variance in outcomes in both time periods resides in the critical role played by external actors. This view represents a serious challenge to much of the existing scholarship that emphasises ASEAN’s ability to defend regional autonomy. As these cases attempt to show, ASEAN autonomy is much more contingent than portrayed in the existing literature.

Keywords: ASEAN, east timor, intervention, sovereignty

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186 Neuropsychiatric Outcomes of Intensive Music Therapy in Stroke Rehabilitation A Premilitary Investigation

Authors: Honey Bryant, Elvina Chu

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Stroke is the leading cause of disability in adults in Canada and directly related to depression, anxiety, and sleep disorders; with an estimated annual cost of $50 billion in health care. Strokes not only impact the individual but society as a whole. Current stroke rehabilitation does not include Music Therapy, although it has success in clinical research in the use of stroke rehabilitation. This study examines the use of neurologic music therapy (NMT) in conjunction with stroke rehabilitation to improve sleep quality, reduce stress levels, and promote neurogenesis. Existing research on NMT in stroke is limited, which means any conclusive information gathered during this study will be significant. My novel hypotheses are a.) stroke patients will become less depressed and less anxious with improved sleep following NMT. b.) NMT will reduce stress levels and promote neurogenesis in stroke patients admitted for rehabilitation. c.) Beneficial effects of NMT will be sustained at least short-term following treatment. Participants were recruited from the in-patient stroke rehabilitation program at Providence Care Hospital in Kingston, Ontario, Canada. All participants-maintained stroke rehabilitation treatment as normal. The study was spilt into two groups, the first being Passive Music Listening (PML) and the second Neurologic Music Therapy (NMT). Each group underwent 10 sessions of intensive music therapy lasting 45 minutes for 10 consecutive days, excluding weekends. Psychiatric Assessments, Epworth Sleepiness Scale (ESS), Hospital Anxiety & Depression Rating Scale (HADS), and Music Engagement Questionnaire (MusEQ), were completed, followed by a general feedback interview. Physiological markers of stress were measured through blood pressure measurements and heart rate variability. Serum collections reviewed neurogenesis via Brain-derived neurotrophic factor (BDNF) and stress markers of cortisol levels. As this study is still on-going, a formal analysis of data has not been fully completed, although trends are following our hypotheses. A decrease in sleepiness and anxiety is seen upon the first cohort of PML. Feedback interviews have indicated most participants subjectively felt more relaxed and thought PML was useful in their recovery. If the hypothesis is supported, larger external funding which will allow for greater investigation of the use of NMT in stroke rehabilitation. As we know, NMT is not covered under Ontario Health Insurance Plan (OHIP), so there is limited scientific data surrounding its uses as a clinical tool. This research will provide detailed findings of the treatment of neuropsychiatric aspects of stroke. Concurrently, a passive music listening study is being designed to further review the use of PML in rehabilitation as well.

Keywords: music therapy, psychotherapy, neurologic music therapy, passive music listening, neuropsychiatry, counselling, behavioural, stroke, stroke rehabilitation, rehabilitation, neuroscience

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185 Towards a Strategic Framework for State-Level Epistemological Functions

Authors: Mark Darius Juszczak

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While epistemology, as a sub-field of philosophy, is generally concerned with theoretical questions about the nature of knowledge, the explosion in digital media technologies has resulted in an exponential increase in the storage and transmission of human information. That increase has resulted in a particular non-linear dynamic – digital epistemological functions are radically altering how and what we know. Neither the rate of that change nor the consequences of it have been well studied or taken into account in developing state-level strategies for epistemological functions. At the current time, US Federal policy, like that of virtually all other countries, maintains, at the national state level, clearly defined boundaries between various epistemological agencies - agencies that, in one way or another, mediate the functional use of knowledge. These agencies can take the form of patent and trademark offices, national library and archive systems, departments of education, departments such as the FTC, university systems and regulations, military research systems such as DARPA, federal scientific research agencies, medical and pharmaceutical accreditation agencies, federal funding for scientific research and legislative committees and subcommittees that attempt to alter the laws that govern epistemological functions. All of these agencies are in the constant process of creating, analyzing, and regulating knowledge. Those processes are, at the most general level, epistemological functions – they act upon and define what knowledge is. At the same time, however, there are no high-level strategic epistemological directives or frameworks that define those functions. The only time in US history where a proxy state-level epistemological strategy existed was between 1961 and 1969 when the Kennedy Administration committed the United States to the Apollo program. While that program had a singular technical objective as its outcome, that objective was so technologically advanced for its day and so complex so that it required a massive redirection of state-level epistemological functions – in essence, a broad and diverse set of state-level agencies suddenly found themselves working together towards a common epistemological goal. This paper does not call for a repeat of the Apollo program. Rather, its purpose is to investigate the minimum structural requirements for a national state-level epistemological strategy in the United States. In addition, this paper also seeks to analyze how the epistemological work of the multitude of national agencies within the United States would be affected by such a high-level framework. This paper is an exploratory study of this type of framework. The primary hypothesis of the author is that such a function is possible but would require extensive re-framing and reclassification of traditional epistemological functions at the respective agency level. In much the same way that, for example, DHS (Department of Homeland Security) evolved to respond to a new type of security threat in the world for the United States, it is theorized that a lack of coordination and alignment in epistemological functions will equally result in a strategic threat to the United States.

Keywords: strategic security, epistemological functions, epistemological agencies, Apollo program

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184 A Comparative Approach for Modeling the Toxicity of Metal Mixtures in Two Ecologically Related Three-Spined (Gasterosteus aculeatus L.) And Nine-Spined (Pungitius pungitius L.) Sticklebacks

Authors: Tomas Makaras

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Sticklebacks (Gasterosteiformes) are increasingly used in ecological and evolutionary research and become well-established role as model species for biologists. However, ecotoxicology studies concerning behavioural effects in sticklebacks regarding stress responses, mainly induced by chemical mixtures, have hardly been addressed. Moreover, although many authors in their studies emphasised the similarity between three-spined and nine-spined stickleback in morphological, neuroanatomical and behavioural adaptations to environmental changes, several comparative studies have revealed considerable differences between these species in and their susceptibility and resistance to variousstressors in laboratory experiments. The hypothesis of this study was that three-spined and nine-spined stickleback species will demonstrate apparent differences in response patterns and sensitivity to metal-based chemicals stimuli. For this purpose, we investigated the swimming behaviour (including mortality rate based on 96-h LC50 values) of two ecologically similar three-spined (Gasterosteusaculeatus) and nine-spined sticklebacks (Pungitiuspungitius) to short-term (up to 24 h) metal mixture (MIX) exposure. We evaluated the relevance and efficacy of behavioural responses of test species in the early toxicity assessment of chemical mixtures. Fish exposed to six (Zn, Pb, Cd, Cu, Ni and Cr) metals in the mixture were either singled out by the Water Framework Directive as priority or as relevant substances in surface water, which was prepared according to the environmental quality standards (EQSs) of these metals set for inland waters in the European Union (EU) (Directive 2013/39/EU). Based on acute toxicity results, G. aculeatus found to be slightly (1.4-fold) more tolerant of MIX impact than those of P. pungitius specimens. The performed behavioural analysis showed the main effect on the interaction between time, species and treatment variables. Although both species exposed to MIX revealed a decreasing tendency in swimming activity, these species’ responsiveness to MIX was somewhat different. Substantial changes in the activity of G. aculeatus were established after 3-h exposure to MIX solutions, which was 1.43-fold lower, while in the case of P. pungitius, 1.96-fold higher than established 96-h LC50 values for each species. This study demonstrated species-specific differences in response sensitivity to metal-based water pollution, indicating behavioural insensitivity of P. pungitiuscompared to G. aculeatus. While many studies highlight the usefulness and suitability of nine-spined sticklebacks for evolutionary and ecological research, attested by their increasing popularity in these fields, great caution must be exercised when using them as model species in ecotoxicological research to probe metal contamination. Meanwhile, G. aculeatus showed to be a promising bioindicator species in the environmental ecotoxicology field.

Keywords: acute toxicity, comparative behaviour, metal mixture, swimming activity

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183 The Porcine Reproductive and Respiratory Syndrome Virus Genotype 2 (PRRSV-2)-derived Oncolytic Protein Reprograms Tumor-Associated Macrophages

Authors: Farrah Putri Salmanida, Mei-Li Wu, Rika Wahyuningtyas, Wen-Bin Chung, Hso-Chi Chaung, Ko-Tung Chang

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Within the field of immunotherapy, oncolytic virotherapy (OVT) employs dual approaches that directly eliminate tumor cells while preserving healthy ones and indirectly reprogram the tumor microenvironment (TME) to elicit antitumor responses. Within the TME, tumor associated macrophages (TAMs) manifest characteristics akin to those of anti-inflammatory M2 macrophages, thus earning the designation of M2-like TAMs. In prior research, two antigens denoted as A1 (g6Ld10T) and A3 (ORF6L5), derived from a complete sequence of ORF5 with partial sequence of ORF6 in Porcine Reproductive and Respiratory Syndrome Virus Genotype 2 (PRRSV-2), demonstrated the capacity to repolarize M2-type porcine alveolar macrophages (PAMs) into M1 phenotypes. In this study, we sought for utilizing OVT strategies by introducing A1 or A3 on TAMs to endow them with the anti-tumor traits of M1 macrophages while retaining their capacity to target cancer cells. Upon exposing human THP-1-derived M2 macrophages to a cross-species test with 2 µg/ml of either A1 or A3 for 24 hours, real time PCR revealed that A3, but not A1, treated cells exhibited upregulated gene expressions of M1 markers (CCR7, IL-1ß, CCL2, Cox2, CD80). These cells reacted to virus-derived antigen, as evidenced by increased expression of pattern-recognition receptors TLR3, TLR7, and TLR9, subsequently providing feedback in the form of type I interferon responses like IFNAR1, IFN-ß, IRF3, IRF7, OAS1, Mx1, and ISG15. Through an MTT assay, only after 15 µg/ml of A3 treatment could the cell viability decrease, with a predicted IC50 of 16.96 µg/ml. Interestingly, A3 caused dose-dependent toxicity to a rat C6 glial cancer cell line even at doses as low as 2.5 µg/ml and reached its IC50 at 9.419 µg/ml. Using Annexin V/7AAD staining and PCR test, we deduced that a significant proportion of C6 cells were undergoing the early apoptosis phase predominantly through the intrinsic apoptosis cascade involving Bcl-2 family proteins. Following this stage, we conducted a test on A3’s repolarization ability, which revealed a significant rise in M1 gene expression markers, such as TNF, CD80, and IL-1ß, in M2-like TAMs generated in vitro from murine RAW264.7 macrophages grown with conditioned medium of 4T1 breast cancer cells. This was corroborated by the results of transcriptome analysis, which revealed that the primary subset among the top 10 to top 30 significantly upregulated differentially expressed genes (DEGs) dominantly consisted of M1 macrophages profiles, including Ccl3, Ccl4, Csf3, TNF, Bcl6b, Stc1, and Dusp2. Our findings unveiled the remarkable potential of the PRRSV-derived antigen A3 to repolarize macrophages while also being capable of selectively inducing apoptosis in cancerous cells. While further in vivo study is needed for A3, it holds promise as an adjuvant by its dual effects in cancer therapy modalities.

Keywords: cancer cell apoptosis, interferon responses, macrophage repolarization, recombinant protein

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182 The Structuring of Economic of Brazilian Innovation and the Institutional Proposal to the Legal Management for Global Conformity to Treat the Technological Risks

Authors: Daniela Pellin, Wilson Engelmann

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Brazil has sought to accelerate your development through technology and innovation as a response to the global influences, which has received in internal management practices. For this, it had edited the Brazilian Law of Innovation 13.243/2016. However observing the Law overestimated economic aspects the respective application will not consider the stakeholders and the technological risks because there is no legal treatment. The economic exploitation and the technological risks must be controlled by limits of democratic system to find better social development to contribute with the economics agents for making decision to conform with global directions. The research understands this is a problem to face given the social particularities of the country because there has been the literal import of the North American Triple Helix Theory consolidated in developed countries and the negative consequences when applied in developing countries. Because of this symptomatic scenario, it is necessary to create adjustment to conduct the management of the law besides social democratic interests to increase the country development. For this, therefore, the Government will have to adopt some conducts promoting side by side with universities, civil society and companies, informational transparency, catch of partnerships, create a Confort Letter document for preparation to ensure the operation, joint elaboration of a Manual of Good Practices, make accountability and data dissemination. Also the Universities must promote informational transparency, drawing up partnership contracts and generating revenue, development of information. In addition, the civil society must do data analysis about proposals received for discussing to give opinion related. At the end, companies have to give public and transparent information about investments and economic benefits, risks and innovation manufactured. The research intends as a general objective to demonstrate that the efficiency of the propeller deployment will be possible if the innovative decision-making process goes through the institutional logic. As specific objectives, the American influence must undergo some modifications to better suit the economic-legal incentives to potentiate the development of the social system. The hypothesis points to institutional model for application to the legal system can be elaborated based on emerging characteristics of the country, in such a way that technological risks can be foreseen and there will be global conformity with attention to the full development of society as proposed by the researchers.The method of approach will be the systemic-constructivist with bibliographical review, data collection and analysis with the construction of the institutional and democratic model for the management of the Law.

Keywords: development, governance of law, institutionalization, triple helix

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181 Growing Pains and Organizational Development in Growing Enterprises: Conceptual Model and Its Empirical Examination

Authors: Maciej Czarnecki

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Even though growth is one of the most important strategic objectives for many enterprises, we know relatively little about this phenomenon. This research contributes to broaden our knowledge of managerial consequences of growth. Scales for measuring organizational development and growing pains were developed. Conceptual model of connections among growth, organizational development, growing pains, selected development factors and financial performance were examined. The research process contained literature review, 20 interviews with managers, examination of 12 raters’ opinions, pilot research and 7 point Likert scale questionnaire research on 138 Polish enterprises employing 50-249 people which increased their employment at least by 50% within last three years. Factor analysis, Pearson product-moment correlation coefficient, student’s t-test and chi-squared test were used to develop scales. High Cronbach’s alpha coefficients were obtained. The verification of correlations among the constructs was carried out with factor correlations, multiple regressions and path analysis. When the enterprise grows, it is necessary to implement changes in its structure, management practices etc. (organizational development) to meet challenges of growing complexity. In this paper, organizational development was defined as internal changes aiming to improve the quality of existing or to introduce new elements in the areas of processes, organizational structure and culture, operational and management systems. Thus; H1: Growth has positive effects on organizational development. The main thesis of the research is that if organizational development does not catch up with growing complexity of growing enterprise, growing pains will arise (lower work comfort, conflicts, lack of control etc.). They will exert a negative influence on the financial performance and may result in serious organizational crisis or even bankruptcy. Thus; H2: Growth has positive effects on growing pains, H3: Organizational development has negative effects on growing pains, H4: Growing pains have negative effects on financial performance, H5: Organizational development has positive effects on financial performance. Scholars considered long lists of factors having potential influence on organizational development. The development of comprehensive model taking into account all possible variables may be beyond the capacity of any researcher or even statistical software used. After literature review, it was decided to increase the level of abstraction and to include following constructs in the conceptual model: organizational learning (OL), positive organization (PO) and high performance factors (HPF). H1a/b/c: OL/PO/HPF has positive effect on organizational development, H2a/b/c: OL/PO/HPF has negative effect on growing pains. The results of hypothesis testing: H1: partly supported, H1a/b/c: supported/not supported/supported, H2: not supported, H2a/b/c: not supported/partly supported/not supported, H3: supported, H4: partly supported, H5: supported. The research seems to be of a great value for both scholars and practitioners. It proved that OL and HPO matter for organizational development. Scales for measuring organizational development and growing pains were developed. Its main finding, though, is that organizational development is a good way of improving financial performance.

Keywords: organizational development, growth, growing pains, financial performance

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180 (Anti)Depressant Effects of Non-Steroidal Antiinflammatory Drugs in Mice

Authors: Horia Păunescu

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Purpose: The study aimed to assess the depressant or antidepressant effects of several Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) in mice: the selective cyclooxygenase-2 (COX-2) inhibitor meloxicam, and the non-selective COX-1 and COX-2 inhibitors lornoxicam, sodium metamizole, and ketorolac. The current literature data regarding such effects of these agents are scarce. Materials and methods: The study was carried out on NMRI mice weighing 20-35 g, kept in a standard laboratory environment. The study was approved by the Ethics Committee of the University of Medicine and Pharmacy „Carol Davila”, Bucharest. The study agents were injected intraperitoneally, 10 mL/kg body weight (bw) 1 hour before the assessment of the locomotor activity by cage testing (n=10 mice/ group) and 2 hours before the forced swimming tests (n=15). The study agents were dissolved in normal saline (meloxicam, sodium metamizole), ethanol 11.8% v/v in normal saline (ketorolac), or water (lornoxicam), respectively. Negative and positive control agents were also given (amitryptilline in the forced swimming test). The cage floor used in the locomotor activity assessment was divided into 20 equal 10 cm squares. The forced swimming test involved partial immersion of the mice in cylinders (15/9cm height/diameter) filled with water (10 cm depth at 28C), where they were left for 6 minutes. The cage endpoint used in the locomotor activity assessment was the number of treaded squares. Four endpoints were used in the forced swimming test (immobility latency for the entire 6 minutes, and immobility, swimming, and climbing scores for the final 4 minutes of the swimming session), recorded by an observer that was "blinded" to the experimental design. The statistical analysis used the Levene test for variance homogeneity, ANOVA and post-hoc analysis as appropriate, Tukey or Tamhane tests.Results: No statistically significant increase or decrease in the number of treaded squares was seen in the locomotor activity assessment of any mice group. In the forced swimming test, amitryptilline showed an antidepressant effect in each experiment, at the 10 mg/kg bw dosage. Sodium metamizole was depressant at 100 mg/kg bw (increased the immobility score, p=0.049, Tamhane test), but not in lower dosages as well (25 and 50 mg/kg bw). Ketorolac showed an antidepressant effect at the intermediate dosage of 5 mg/kg bw, but not so in the dosages of 2.5 and 10 mg/kg bw, respectively (increased the swimming score, p=0.012, Tamhane test). Meloxicam and lornoxicam did not alter the forced swimming endpoints at any dosage level. Discussion: 1) Certain NSAIDs caused changes in the forced swimming patterns without interfering with locomotion. 2) Sodium metamizole showed a depressant effect, whereas ketorolac proved antidepressant. Conclusion: NSAID-induced mood changes are not class effects of these agents and apparently are independent of the type of inhibited cyclooxygenase (COX-1 or COX-2). Disclosure: This paper was co-financed from the European Social Fund, through the Sectorial Operational Programme Human Resources Development 2007-2013, project number POSDRU /159 /1.5 /S /138907 "Excellence in scientific interdisciplinary research, doctoral and postdoctoral, in the economic, social and medical fields -EXCELIS", coordinator The Bucharest University of Economic Studies.

Keywords: antidepressant, depressant, forced swim, NSAIDs

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179 Burnout in the Resident Physician and a Simple Means of Improvement

Authors: Jacob Dangerfield, Jacob Pollard, Jennifer DeCou

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Introduction: Burnout, anxiety, and depression are three conditions that are prevalent in medical providers. This is especially the case in the field of anesthesia, which has a high number of providers suffering from burnout and burnout syndrome. A major contributor to this issue is isolation in the workplace, with a perceived lack of peer support as a major risk factor for burnout. Two organizational interventions that can be done to help improve this issue are small group sessions and providing affordable mental health services. Per American College of Graduate Medical Education (ACGME) Guidelines, these affordable mental health services are a requirement of all residency programs, but for a variety of reasons, many residents do not access them. As physicians, we are often not good at asking for help. With this in mind, we hypothesized that carrying out small group resiliency sessions facilitated by Graduate Medical Education (GME) Wellness Counselors would improve both resident peer support as well as the likelihood that a resident will reach out to GME Wellness in a time of need. Methods: We held small group resiliency sessions with the GME Wellness Mental Health Professionals during protected didactic time. These sessions were small groups, including the members of one’s class (i.e., first-year residents on their own), and were facilitated by 1-2 mental health professionals. After these sessions, we surveyed residents who attended using a short Google Forms survey and using a 5-point Likert Scale, asked residents about some outcomes from the session. A “strongly agree” or “agree” was considered a positive response. Results: Results from our survey showed that the resident sessions had multiple positive outcomes. This survey was sent to 29 residents, and we had a 62% response rate. We found out through this survey that these small group sessions had a perceived positive impact on resident personal well-being, increased perceived peer support from classmates, and made residents more likely to reach out to GME Wellness in the future. Perceived positive impact on well-being was found in 83% of resident respondents, improved perceived peer support in 83% of respondents, and 78% of resident respondents stated that this session increased their likelihood of reaching out to mental health professionals. Conclusions: Through this study, we can conclude that our hypothesis was correct in that Small Group Resiliency Sessions that are facilitated by GME Wellness Counselors improve both resident peer support as well as the likelihood a resident reaches out to these mental health professionals in time of need. We believe these findings are very important as they address two important factors that can aid in decreasing a provider’s risk of experiencing burnout. Through this simple means, we believe other residency programs can help the well-being of their residents, and together, we can decrease the number of cases of burnout in anesthesia.

Keywords: anesthesiology, burnout, wellness, depression, residents, trainees, mental health

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178 Contrastive Focus Marking in Brazilian Children under Typical and Atypical Phonological Development

Authors: Geovana Soncin, Larissa Berti

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Some aspects of prosody acquisition remain still unclear, especially regarding atypical speech development processes. This work deals with prosody acquisition and its implications for clinical purposes. Therefore, we analyze speech samples produced by adult speakers, children in typical language development, and children with phonological disorders. Phonological disorder comprises deviating manifestations characterized by inconsistencies in the phonological representation of a linguistic system under acquisition. The clinical assessment is performed mostly based on contrasts whose manifestations occur in the segmental level of a phonological system. Prosodic organization of spoken utterances is not included in the standard assessment. However, assuming that prosody is part of the phonological system, it was hypothesized that children with Phonological Disorders could present inconsistencies that also occur at a prosodic level. Based on this hypothesis, the paper aims to analyze contrastive focus marking in the speech of children with Phonological Disorders in comparison with the speech of children under Typical Language Development and adults. The participants of all groups were native speakers of Brazilian Portuguese. The investigation was designed in such a way as to identify differences and similarities among the groups that could be interpreted as clues of normal or deviant processes of prosody acquisition. Contrastive focus in Brazilian Portuguese is marked by increasing duration, f0, and intensity on the focused element as well as by a particular type of pitch accent (L*+H). Thirty-nine subjects participated, thirteen from each group. Acoustic analysis was performed, considering duration, intensity, and intonation as parameters. Children with PD were recruited in sessions from a service provided by Speech-Language Pathology Therapy; children in TD, paired in age and sex with the first group, were recruited in a regular school; and 20-24 years old adults were recruited from a University class. In a game prepared to elicit focused sentences, all of them produced the sentence “Girls love red dress,” marking focus on different syntactic positions: subject, verb, and object. Results showed that adults, children in typical language development, and children with Phonological Disorders marked contrastive focus differently: typical children used all parameters like adults do; however, in comparison with them, they exaggerated duration and, in the opposite direction, they did not increase f0 in a sufficient magnitude as adults; children with Phonological Disorder presented inconsistencies in duration, not increasing it in some syntactic positions, and also in intonation, not producing the representative pitch accent of contrastive focus. The results suggest prosody is also affected by phonological disorder and give clues of developmental processes of prosody acquisition.

Keywords: Brazilian Portuguese, contrastive focus, phonological disorder, prosody acquisition

Procedia PDF Downloads 86
177 Investigating the English Speech Processing System of EFL Japanese Older Children

Authors: Hiromi Kawai

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This study investigates the nature of EFL older children’s L2 perceptive and productive abilities using classroom data, in order to find a pedagogical solution to the teaching of L2 sounds at an early stage of learning in a formal school setting. It is still inconclusive whether older children with only EFL formal school instruction at the initial stage of L2 learning are able to attain native-like perception and production in English within the very limited amount of exposure to the target language available. Based on the notion of the lack of study of EFL Japanese children’s acquisition of English segments, the researcher uses a model of L1 speech processing which was developed for investigating L1 English children’s speech and literacy difficulties using a psycholinguistic framework. The model is composed of input channel, output channel, and lexical representation, and examines how a child receives information from spoken or written language, remembers and stores it within the lexical representations and how the child selects and produces spoken or written words. Concerning language universality and language specificity in the language acquisitional process, the aim of finding any sound errors in L1 English children seemed to conform to the author’s intention to find abilities of English sounds in older Japanese children at the novice level of English in an EFL setting. 104 students in Grade 5 (between the ages of 10 and 11 years old) of an elementary school in Tokyo participated in this study. Four tests to measure their perceptive ability and three oral repetition tests to measure their productive ability were conducted with/without reference to lexical representation. All the test items were analyzed to calculate item facility (IF) indices, and correlational analyses and Structural Equation Modeling (SEM) were conducted to examine the relationship between the receptive ability and the productive ability. IF analysis showed that (1) the participants were better at perceiving a segment than producing a segment, (2) they had difficulty in auditory discrimination of paired consonants when one of them does not exist in the Japanese inventory, (3) they had difficulty in both perceiving and producing English vowels, and (4) their L1 loan word knowledge had an influence on their ability to perceive and produce L2 sounds. The result of the Multiple Regression Modeling showed that the two production tests could predict the participants’ auditory ability of real words in English. The result of SEM showed that the hypothesis that perceptive ability affects productive ability was supported. Based on these findings, the author discusses the possible explicit method of teaching English segments to EFL older children in a formal school setting.

Keywords: EFL older children, english segments, perception, production, speech processing system

Procedia PDF Downloads 243
176 Determinants of Long Acting Reversible Contraception Utilization among Women (15-49) in Uganda: Analysis of 2016 PMA2020 Uganda Survey

Authors: Nulu Nanono

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Background: The Ugandan national health policy and the national population policy all recognize the need to increase access to quality, affordable, acceptable and sustainable contraceptive services for all people but provision and utilization of quality services remains low. Two contraceptive methods are categorized as long-acting temporary methods: intrauterine contraceptive devices (IUCDs) and implants. Copper-containing IUCDs, generally available in Ministry of Health (MoH) family planning programs and is effective for at least 12 years while Implants, depending on the type, last for up to three to seven years. Uganda’s current policy and political environment are favorable towards achieving national access to quality and safe contraceptives for all people as evidenced by increasing government commitments and innovative family planning programs. Despite the increase of modern contraception use from 14% to 26%, long acting reversible contraceptive (LARC) utilization has relatively remained low with less than 5% using IUDs & Implants which in a way explains Uganda’s persistent high fertility rates. Main question/hypothesis: The purpose of the study was to examine relationship between the demographic, socio-economic characteristics of women, health facility factors and long acting reversible contraception utilization. Methodology: LARC utilization was investigated comprising of the two questions namely are you or your partner currently doing something or using any method to delay or avoid getting pregnant? And which method or methods are you using? Data for the study was sourced from the 2016 Uganda Performance Monitoring and Accountability 2020 Survey comprising of 3816 female respondents aged 15 to 49 years. The analysis was done using the Chi-squared tests and the probit regression at bivariate and multivariate levels respectively. The model was further tested for validity and normality of the residuals using the Sharipo wilks test and test for kurtosis and skewness. Results: The results showed the model the age, parity, marital status, region, knowledge of LARCs, availability of LARCs to be significantly associated with long acting contraceptive utilization with p value of less than 0.05. At the multivariate analysis level, women who had higher parities (0.000) tertiary education (0.013), no knowledge about LARCs (0.006) increases their probability of using LARCs. Furthermore while women age 45-49, those who live in the eastern region reduces their probability of using LARCs. Knowledge contribution: The findings of this study join the debate of prior research in this field and add to the body of knowledge related to long acting reversible contraception. An outstanding and queer finding from the study is the non-utilization of LARCs by women who are aware and have knowledge about them, this may be an opportunity for further research to investigate the attribution to this.

Keywords: contraception, long acting, utilization, women (15-49)

Procedia PDF Downloads 204
175 Information Seeking and Evaluation Tasks to Enhance Multiliteracies in Health Education

Authors: Tuula Nygard

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This study contributes to the pedagogical discussion on how to promote adolescents’ multiliteracies with the emphasis on information seeking and evaluation skills in contemporary media environments. The study is conducted in the school environment utilizing perspectives of educational sciences and information studies to health communication and teaching. The research focus is on the teacher role as a trusted person, who guides students to choose and use credible information sources. Evaluating the credibility of information may often be challenging. Specifically, children and adolescents may find it difficult to know what to believe and who to trust, for instance, in health and well-being communication. Thus, advanced multiliteracy skills are needed. In the school environment, trust is based on the teacher’s subject content knowledge, but also the teacher’s character and caring. Teacher’s benevolence and approachability generate trustworthiness, which lays the foundation for good interaction with students and further, for the teacher’s pedagogical authority. The study explores teachers’ perceptions of their pedagogical authority and the role of a trustee. In addition, the study examines what kind of multiliteracy practices teachers utilize in their teaching. The data will be collected by interviewing secondary school health education teachers during Spring 2019. The analysis method is a nexus analysis, which is an ethnographic research orientation. Classroom interaction as the interviewed teachers see it is scrutinized through a nexus analysis lens in order to expound a social action, where people, places, discourses, and objects are intertwined. The crucial social actions in this study are information seeking and evaluation situations, where the teacher and the students together assess the credibility of the information sources. The study is based on the hypothesis that a trustee’s opinions of credible sources and guidance in information seeking and evaluation affect students’, that is, trustors’ choices. In the school context, the teacher’s own experiences and perceptions of health-related issues cannot be brushed aside. Furthermore, adolescents are used to utilize digital technology for day-to-day information seeking, but the chosen information sources are often not very high quality. In the school, teachers are inclined to recommend familiar sources, such as health education textbook and web pages of well-known health authorities. Students, in turn, rely on the teacher’s guidance of credible information sources without using their own judgment. In terms of students’ multiliteracy competences, information seeking and evaluation tasks in health education are excellent opportunities to practice and enhance these skills. To distinguish the right information from a wrong one is particularly important in health communication because experts by experience are easy to find and their opinions are convincing. This can be addressed by employing the ideas of multiliteracy in the school subject health education and in teacher education and training.

Keywords: multiliteracies, nexus analysis, pedagogical authority, trust

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174 Effect of Chitosan Oligosaccharide from Tenebrio Molitor on Prebiotics

Authors: Hyemi Kim, Jay Kim, Kyunghoon Han, Ra-Yeong Choi, In-Woo Kim, Hyung Joo Suh, Ki-Bae Hong, Sung Hee Han

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Chitosan is used in various industries such as food and medical care because it is known to have various functions such as anti-obesity, anti-inflammatory and anti-cancer benefits. Most of the commercial chitosan is extracted from crustaceans. As the harvest rate of snow crabs and red snow crabs decreases and safety issues arise due to environmental pollution, research is underway to extract chitosan from insects. In this study, we used Response Surface Methodology (RSM) to predict the optimal conditions to produce chitosan oligosaccharides from mealworms (MCOS), which can be absorbed through the intestine as low-molecular-weight chitosan. The experimentally confirmed optimal conditions for MCOS production using chitosanase were found to be a substrate concentration of 2.5%, enzyme addition of 30 mg/g and a reaction time of 6 hours. The chemical structure and physicochemical properties of the produced MCOS were measured using MALDI-TOF mass spectra and FTIR spectra. The MALDI-TOF mass spectra revealed peaks corresponding to the dimer (375.045), trimer (525.214), tetramer (693.243), pentamer (826.296), and hexamer (987.360). In the FTIR spectra, commercial chitosan oligosaccharides exhibited a weak peak pattern at 3500-2500 cm-1, unlike chitosan or chitosan oligosaccharides. There was a difference in the peak at 3200~3500 cm-1, where different vibrations corresponding to OH and amine groups overlapped. Chitosan, chitosan oligosaccharide, and commercial chitosan oligosaccharide showed peaks at 2849, 2884, and 2885 cm-1, respectively, attributed to the absorption of the C-H stretching vibration of methyl or methine. The amide I, amide II, and amide III bands of chitosan, chitosan oligosaccharide, and commercial chitosan oligosaccharide exhibited peaks at 1620/1620/1602, 1553/1555/1505, and 1310/1309/1317 cm-1, respectively. Furthermore, the solubility of MCOS was 45.15±3.43, water binding capacity (WBC) was 299.25±4.57, and fat binding capacity (FBC) was 325.61±2.28 and the solubility of commercial chitosan oligosaccharides was 49.04±9.52, WBC was 280.55±0.50, and FBC was 157.22±18.15. Thus, the characteristics of MCOS and commercial chitosan oligosaccharides are similar. The results of investigating the impact of chitosan oligosaccharide on the proliferation of probiotics revealed increased growth in L. casei, L. acidophilus, and Bif. Bifidum. Therefore, the major short-chain fatty acids produced by gut microorganisms, such as acetic acid, propionic acid, and butyric acid, increased within 24 hours of adding 1% (p<0.01) and 2% (p<0.001) MCOS. The impact of MCOS on the overall gut microbiota was assessed, revealing that the Chao1 index did not show significant differences, but the Simpson index decreased in a concentration-dependent manner, indicating a higher species diversity. The addition of MCOS resulted in changes in the overall microbial composition, with an increase in Firmicutes and Verrucomicrobia (p<0.05) compared to the control group, while Proteobacteria and Actinobacteria (p<0.05) decreased. At the genus level, changes in microbiota due to MCOS supplementation showed an increase in beneficial bacteria like lactobacillus, Romboutsia, Turicibacter, and Akkermansia (p<0.0001) while harmful bacteria like Enterococcus, Morganella, Proterus, and Bacteroides (p<0.0001) decreased. In this study, chitosan oligosaccharides were successfully produced under established conditions from mealworms, and these chitosan oligosaccharides are expected to have prebiotic effects, similar to those obtained from crabs.

Keywords: mealworms, chitosan, chitosan oligosaccharide, prebiotics

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173 Organ Donation after Medical Aid in Dying: A Critical Study of Clinical Processes and Legal Rules in Place

Authors: Louise Bernier

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Under some jurisdictions (including Canada), eligible patients can request and receive medical assistance in dying (MAiD) through lethal injections, inducing their cardiocirculatory death. Those same patients can also wish to donate their organs in the process. If they qualify as organ donors, a clinical and ethical rule called the 'dead donor rule' (DDR) requires the transplant teams to wait after cardiocirculatory death is confirmed, followed by a 'no touch' period (5 minutes in Canada) before they can proceed with organ removal. The medical procedures (lethal injections) as well as the delays associated with the DDR can damage organs (mostly thoracic organs) due to prolonged anoxia. Yet, strong scientific evidences demonstrate that operating differently and reconsidering the DDR would result in more organs of better quality available for transplant. This idea generates discomfort and resistance, but it is also worth considering, especially in a context of chronic shortage of available organs. One option that could be examined for MAiD’ patients who wish and can be organ donors would be to remove vital organs while patients are still alive (and under sedation). This would imply accepting that patient’s death would occur through organ donation instead of lethal injections required under MAiD’ legal rules. It would also mean that patients requesting MAiD and wishing to be organ donors could aspire to donate better quality organs, including their heart, an altruistic gesture that carries important symbolic value for many donors and their families. Following a patient centered approach, our hypothesis is that preventing vital organ donation from a living donor in all circumstance is neither perfectly coherent with how legal mentalities have evolved lately in the field of fundamental rights nor compatible with the clinical and ethical frameworks that shape the landscape in which those complex medical decisions unfold. Through a study of the legal, ethical, and clinical rules in place, both at the national and international levels, this analysis raises questions on the numerous inconsistencies associated with respecting the DDR with patients who have chosen to die through MAiD. We will begin with an assessment of the erosion of certain national legal frameworks that pertain to the sacred nature of the right to life which now also includes the right to choose how one wishes to die. We will then study recent innovative clinical protocols tested in different countries to help address acute organ shortage problems in creative ways. We will conclude this analysis with an ethical assessment of the situation, referring to principles such as justice, autonomy, altruism, beneficence, and non-malfeasance. This study will build a strong argument in favor of starting to allow vital organ donations from living donors in countries where MAiD is already permitted.

Keywords: altruism, autonomy, dead donor rule, medical assistance in dying, non-malfeasance, organ donation

Procedia PDF Downloads 178
172 The Environmental Impact of Sustainability Dispersion of Chlorine Releases in Coastal Zone of Alexandra: Spatial-Ecological Modeling

Authors: Mohammed El Raey, Moustafa Osman Mohammed

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The spatial-ecological modeling is relating sustainable dispersions with social development. Sustainability with spatial-ecological model gives attention to urban environments in the design review management to comply with Earth’s System. Naturally exchange patterns of ecosystems have consistent and periodic cycles to preserve energy flows and materials in Earth’s System. The probabilistic risk assessment (PRA) technique is utilized to assess the safety of industrial complex. The other analytical approach is the Failure-Safe Mode and Effect Analysis (FMEA) for critical components. The plant safety parameters are identified for engineering topology as employed in assessment safety of industrial ecology. In particular, the most severe accidental release of hazardous gaseous is postulated, analyzed and assessment in industrial region. The IAEA- safety assessment procedure is used to account the duration and rate of discharge of liquid chlorine. The ecological model of plume dispersion width and concentration of chlorine gas in the downwind direction is determined using Gaussian Plume Model in urban and ruler areas and presented with SURFER®. The prediction of accident consequences is traced in risk contour concentration lines. The local greenhouse effect is predicted with relevant conclusions. The spatial-ecological model is also predicted the distribution schemes from the perspective of pollutants that considered multiple factors of multi-criteria analysis. The data extends input–output analysis to evaluate the spillover effect, and conducted Monte Carlo simulations and sensitivity analysis. Their unique structure is balanced within “equilibrium patterns”, such as the biosphere and collective a composite index of many distributed feedback flows. These dynamic structures are related to have their physical and chemical properties and enable a gradual and prolonged incremental pattern. While this spatial model structure argues from ecology, resource savings, static load design, financial and other pragmatic reasons, the outcomes are not decisive in artistic/ architectural perspective. The hypothesis is an attempt to unify analytic and analogical spatial structure for development urban environments using optimization software and applied as an example of integrated industrial structure where the process is based on engineering topology as optimization approach of systems ecology.

Keywords: spatial-ecological modeling, spatial structure orientation impact, composite structure, industrial ecology

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171 The Role of a Biphasic Implant Based on a Bioactive Silk Fibroin for Osteochondral Tissue Regeneration

Authors: Lizeth Fuentes-Mera, Vanessa Perez-Silos, Nidia K. Moncada-Saucedo, Alejandro Garcia-Ruiz, Alberto Camacho, Jorge Lara-Arias, Ivan Marino-Martinez, Victor Romero-Diaz, Adolfo Soto-Dominguez, Humberto Rodriguez-Rocha, Hang Lin, Victor Pena-Martinez

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Biphasic scaffolds in cartilage tissue engineering have been designed to influence not only the recapitulation of the osteochondral architecture but also to take advantage of the healing ability of bone to promote the implant integration with the surrounding tissue and then bone restoration and cartilage regeneration. This study reports the development and characterization of a biphasic scaffold based on the assembly of a cartilage phase constituted by fibroin biofunctionalized with bovine cartilage matrix; cellularized with differentiated pre-chondrocytes from adipose tissue stem cells (autologous) and well attached to a bone phase (bone bovine decellularized) to mimic the structure of the nature of native tissue and to promote the cartilage regeneration in a model of joint damage in pigs. Biphasic scaffolds were assembled by fibroin crystallization with methanol. The histological and ultrastructural architectures were evaluated by optical and scanning electron microscopy respectively. Mechanical tests were conducted to evaluate Young's modulus of the implant. For the biological evaluation, pre-chondrocytes were loaded onto the scaffolds and cellular adhesion, proliferation, and gene expression analysis of cartilage extracellular matrix components was performed. The scaffolds that were cellularized and matured for 10 days were implanted into critical 3 mm in diameter and 9-mm in depth osteochondral defects in a porcine model (n=4). Three treatments were applied per knee: Group 1: monophasic cellular scaffold (MS) (single chondral phase), group 2: biphasic scaffold, cellularized only in the chondral phase (BS1), group 3: BS cellularized in both bone and chondral phases (BS2). Simultaneously, a control without treatment was evaluated. After 4 weeks of surgery, integration and regeneration tissues were analyzed by x-rays, histology and immunohistochemistry evaluation. The mechanical assessment showed that the acellular biphasic composites exhibited Young's modulus of 805.01 kPa similar to native cartilage (400-800 kPa). In vitro biological studies revealed the chondroinductive ability of the biphasic implant, evidenced by an increase in sulfated glycosaminoglycan (GAGs) and type II collagen, both secreted by the chondrocytes cultured on the scaffold during 28 days. No evidence of adverse or inflammatory reactions was observed in the in vivo trial; however, In group 1, the defects were not reconstructed. In group 2 and 3 a good integration of the implant with the surrounding tissue was observed. Defects in group 2 were fulfilled by hyaline cartilage and normal bone. Group 3 defects showed fibrous repair tissue. In conclusion; our findings demonstrated the efficacy of biphasic and bioactive scaffold based on silk fibroin, which entwined chondroinductive features and biomechanical capability with appropriate integration with the surrounding tissue, representing a promising alternative for osteochondral tissue-engineering applications.

Keywords: biphasic scaffold, extracellular cartilage matrix, silk fibroin, osteochondral tissue engineering

Procedia PDF Downloads 153
170 Gender Specific Differences in Clinical Outcomes of Knee Osteoarthritis Treated with Micro-Fragmented Adipose Tissue

Authors: Tiffanie-Marie Borg, Yasmin Zeinolabediny, Nima Heidari, Ali Noorani, Mark Slevin, Angel Cullen, Stefano Olgiati, Alberto Zerbi, Alessandro Danovi, Adrian Wilson

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Knee Osteoarthritis (OA) is a critical cause of disability globally. In recent years, there has been growing interest in non-invasive treatments, such as intra-articular injection of micro-fragmented fat (MFAT), showing great potential in treating OA. Mesenchymal stem cells (MSCs), originating from pericytes of micro-vessels in MFAT, can differentiate into mesenchymal lineage cells such as cartilage, osteocytes, adipocytes, and osteoblasts. Secretion of growth factor and cytokines from MSCs have the capability to inhibit T cell growth, reduced pain and inflammation, and create a micro-environment that through paracrine signaling, can promote joint repair and cartilage regeneration. Here we have shown, for the first time, data supporting the hypothesis that women respond better in terms of improvements in pain and function to MFAT injection compared to men. Historically, women have been underrepresented in studies, and studies with both sexes regularly fail to analyse the results by sex. To mitigate this bias and quantify it, we describe a technique using reproducible statistical analysis and replicable results with Open Access statistical software R to calculate the magnitude of this difference. Genetic, hormonal, environmental, and age factors play a role in our observed difference between the sexes. This observational, intention-to-treat study included the complete sample of 456 patients who agreed to be scored for pain (visual analogue scale (VAS)) and function (Oxford knee score (OKS)) at baseline regardless of subsequent changes to adherence or status during follow-up. We report that a significantly larger number of women responded to treatment than men: [90% vs. 60% change in VAS scores with 87% vs. 65% change in OKS scores, respectively]. Women overall had a stronger positive response to treatment with reduced pain and improved mobility and function. Pre-injection, our cohort of women were in more pain with worse joint function which is quite common to see in orthopaedics. However, during the 2-year follow-up, they consistently maintained a lower incidence of discomfort with superior joint function. This data clearly identifies a clear need for further studies to identify the cell and molecular biological and other basis for these differences and be able to utilize this information for stratification in order to improve outcome for both women and men.

Keywords: gender differences, micro-fragmented adipose tissue, knee osteoarthritis, stem cells

Procedia PDF Downloads 181
169 The Subtle Influence of Hindu Doctrines on Film Industry: A Case Study of Movie Avatar

Authors: Cemil Kutlutürk

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Hindu culture and religious doctrines such as caste, reincarnation, yoga, nirvana have always proved a popular theme for the film industry. The analyzing of these motifs in the movies with a scientific approach enables to individuals either to comprehend the messages and deep meanings of films or to understand others’ religious beliefs systems and daily lives in a properly way. The primary aim of this study is to handle the subtle influence of Hindu doctrines on cinema industry by focusing on James Cameron’s film, Avatar and its relationship with Hindu concept of avatara by referring to original Hindu sacred texts where this doctrine is basically clarified. The Sanskrit word avatara means to come down or to descend. Although an avatara is commonly considered as an appearance of any deity on earth, the term refers the Vishnu’s descending on earth. When the movie avatar and avatara doctrine are compared, various similarities have noteworthy revealed. Firstly in the movie, Jake is chosen by Eywa to protect Pandora from evils. Similarly in the movie, avatar is born when there is a rise of jealousy and unrighteousness. The same concept is found in avatara doctrine. According to this belief whenever righteousness (dharma) wanes and unrighteousness (adharma) increases God incarnates himself as an avatara. In Hindu tradition, the ten avataras of Vishnu are the most popular. This standard list of ten avataras includes the Fish, the Tortoise, the Boar, the Man-Lion (Narasimha), the Dwarf, Parasurama, Rama, Krishna, the Buddha and Kalki. In the movie the avatar has tail, eyes, nose, ear which is similar to Narasimha (half man-half lion) avatara. On the other hand use of bow and arrow by Navis in the film, evokes us Rama avatara whose basic gun is same. Navis fly on a dragon like bird called Ikra and ride a horse-like quadruped animal. The vehicle for transformation of the avatar in the movie is also resemblance with the idea of Garuda, the great mythical bird, which is used by Vishnu in Hindu mythology. In addition, the last avatara, Kalki, will be seen on a white horse according to Puranas. The basic difference is that for Hinduism avatara means descent of a God, yet in the movie, a human being named Jake Sully, is manifested as humanoid of another planet, this is called as avatar. While in the movie the avatar manifests himself in another planet, Pandora, in Hinduism avataras descent on this world. On the other hand, in Hindu scriptures, there are many avataras and they are categorized according to their functions and attributes. These sides of avatara doctrine cannot be also seen clearly in the film. Even though there are some differences between each other, the main hypothesis of this study is that the general character of the movie is similar to avatara doctrine. In the movie instead of emphasizing on a specific avatara, qualities of different Vishnu avataras have been properly used.

Keywords: film industry, Hinduism, incarnation, James Cameron, movie avatar

Procedia PDF Downloads 401
168 Quantum Mechanics as A Limiting Case of Relativistic Mechanics

Authors: Ahmad Almajid

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The idea of unifying quantum mechanics with general relativity is still a dream for many researchers, as physics has only two paths, no more. Einstein's path, which is mainly based on particle mechanics, and the path of Paul Dirac and others, which is based on wave mechanics, the incompatibility of the two approaches is due to the radical difference in the initial assumptions and the mathematical nature of each approach. Logical thinking in modern physics leads us to two problems: - In quantum mechanics, despite its success, the problem of measurement and the problem of wave function interpretation is still obscure. - In special relativity, despite the success of the equivalence of rest-mass and energy, but at the speed of light, the fact that the energy becomes infinite is contrary to logic because the speed of light is not infinite, and the mass of the particle is not infinite too. These contradictions arise from the overlap of relativistic and quantum mechanics in the neighborhood of the speed of light, and in order to solve these problems, one must understand well how to move from relativistic mechanics to quantum mechanics, or rather, to unify them in a way different from Dirac's method, in order to go along with God or Nature, since, as Einstein said, "God doesn't play dice." From De Broglie's hypothesis about wave-particle duality, Léon Brillouin's definition of the new proper time was deduced, and thus the quantum Lorentz factor was obtained. Finally, using the Euler-Lagrange equation, we come up with new equations in quantum mechanics. In this paper, the two problems in modern physics mentioned above are solved; it can be said that this new approach to quantum mechanics will enable us to unify it with general relativity quite simply. If the experiments prove the validity of the results of this research, we will be able in the future to transport the matter at speed close to the speed of light. Finally, this research yielded three important results: 1- Lorentz quantum factor. 2- Planck energy is a limited case of Einstein energy. 3- Real quantum mechanics, in which new equations for quantum mechanics match and exceed Dirac's equations, these equations have been reached in a completely different way from Dirac's method. These equations show that quantum mechanics is a limited case of relativistic mechanics. At the Solvay Conference in 1927, the debate about quantum mechanics between Bohr, Einstein, and others reached its climax, while Bohr suggested that if particles are not observed, they are in a probabilistic state, then Einstein said his famous claim ("God does not play dice"). Thus, Einstein was right, especially when he didn't accept the principle of indeterminacy in quantum theory, although experiments support quantum mechanics. However, the results of our research indicate that God really does not play dice; when the electron disappears, it turns into amicable particles or an elastic medium, according to the above obvious equations. Likewise, Bohr was right also, when he indicated that there must be a science like quantum mechanics to monitor and study the motion of subatomic particles, but the picture in front of him was blurry and not clear, so he resorted to the probabilistic interpretation.

Keywords: lorentz quantum factor, new, planck’s energy as a limiting case of einstein’s energy, real quantum mechanics, new equations for quantum mechanics

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167 Chemical and Electrochemical Syntheses of Two Organic Components of Ginger

Authors: Adrienn Kiss, Karoly Zauer, Gyorgy Keglevich, Rita Molnarne Bernath

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Ginger (Zingiber officinale) is a perennial plant from Southeast Asia, widely used as a spice, herb, and medicine for many illnesses since its beneficial health effects were observed thousands of years ago. Among the compounds found in ginger, zingerone [4-hydroxy-3- methoxyphenyl-2-butanone] deserves special attention: it has an anti-inflammatory and antispasmodic effect, it can be used in case of diarrheal disease, helps to prevent the formation of blood clots, has antimicrobial properties, and can also play a role in preventing the Alzheimer's disease. Ferulic acid [(E)-3-(4-hydroxy-3-methoxyphenyl)-prop-2-enoic acid] is another cinnamic acid derivative in ginger, which has promising properties. Like many phenolic compounds, ferulic acid is also an antioxidant. Based on the results of animal experiments, it is assumed to have a direct antitumoral effect in lung and liver cancer. It also deactivates free radicals that can damage the cell membrane and the DNA and helps to protect the skin against UV radiation. The aim of this work was to synthesize these two compounds by new methods. A few of the reactions were based on the hydrogenation of dehydrozingerone [4-(4-Hydroxy-3-methoxyphenyl)-3-buten-2-one] to zingerone. Dehydrozingerone can be synthesized by a relatively simple method from acetone and vanillin with good yield (80%, melting point: 41 °C). Hydrogenation can be carried out chemically, for example by the reaction of zinc and acetic acid, or Grignard magnesium and ethyl alcohol. Another way to complete the reduction is the electrochemical pathway. The electrolysis of dehydrozingerone without diaphragm in aqueous media was attempted to produce ferulic acid in the presence of sodium carbonate and potassium iodide using platinum electrodes. The electrolysis of dehydrozingerone in the presence of potassium carbonate and acetic acid to prepare zingerone was carried out similarly. Ferulic acid was expected to be converted to dihydroferulic acid [3-(4-Hydroxy-3-methoxyphenyl)propanoic acid] in potassium hydroxide solution using iron electrodes, separating the anode and cathode space with a Soxhlet paper sheath impregnated with saturated magnesium chloride solution. For this reaction, ferulic acid was synthesized from vanillin and malonic acid in the presence of pyridine and piperidine (yield: 88.7%, melting point: 173°C). Unfortunately, in many cases, the expected transformations did not happen or took place in low conversions, although gas evolution occurred. Thus, a deeper understanding of these experiments and optimization are needed. Since both compounds are found in different plants, they can also be obtained by alkaline extraction or steam distillation from distinct plant parts (ferulic acid from ground bamboo shoots, zingerone from grated ginger root). The products of these reactions are rich in several other organic compounds as well; therefore, their separation must be solved to get the desired pure material. The products of the reactions described above were characterized by infrared spectral data and melting points. The use of these two simple methods may be informative for the formation of the products. In the future, we would like to study the ferulic acid and zingerone content of other plants and extract them efficiently. The optimization of electrochemical reactions and the use of other test methods are also among our plans.

Keywords: ferulic acid, ginger, synthesis, zingerone

Procedia PDF Downloads 175
166 Vicarious Cues in Portraying Emotion: Musicians' Self-Appraisal

Authors: W. Linthicum-Blackhorse, P. Martens

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This present study seeks to discover attitudinal commonalities and differences within a musician population relative to the communication of emotion via music. We hypothesized that instrument type, as well as age and gender, would bear significantly on musicians’ opinions. A survey was administered to 178 participants; 152 were current music majors (mean age 20.3 years, 62 female) and 26 were adult participants in a community choir (mean age 54.0 years, 12 female). The adult participants were all vocalists, while student participants represented the full range of orchestral instruments. The students were grouped by degree program, (performance, music education, or other) and instrument type (voice, brass, woodwinds, strings, percussion). The survey asked 'How important are each of the following areas to you for portraying emotion in music?' Participants were asked to rate each of 15 items on a scale of 1 (not at all important) to 10 (very important). Participants were also instructed to leave blank any item that they did not understand. The 15 items were: dynamic contrast, overall volume, phrasing, facial expression, staging (placement), pitch accuracy, tempo changes, bodily movement, your mood, your attitude, vibrato, rubato, stage/room lighting, clothing type, and clothing color. Contrary to our hypothesis, there was no overall effect of gender or age, and neither did any single response item show a significant difference due to these subject parameters. Among the student participants, however, one-way ANOVA revealed a significant effect of degree program on the rated importance of four items: dynamic contrast, tempo changes, vibrato, and rubato. Significant effects of instrument type were found in the responses to eight items: facial expression, staging, body movement, vibrato, rubato, lighting, clothing type, and clothing color. Post hoc comparisons (Tukey) show that some variation follows from obvious differences between instrument types (e.g. string players are more concerned with vibrato than everyone but woodwind players; vocalists are significantly more concerned with facial expression than everyone but string players), but other differences could point to communal mindsets toward vicarious cues within instrument type. These mindsets could be global (e.g. brass players deeming body movement significantly less important than string players, being less often featured as soloists and appearing less often at the front of the stage) or local (e.g. string players being significantly more concerned than all other groups about both clothing color and type, perhaps due to the strongly-expressed opinions of specific teachers). Future work will attempt to identify the source of these self-appraisals, whether enculturated via explicit pedagogy, or whether absorbed from individuals' observations and performance experience.

Keywords: performance, vicarious cues, communication, emotion

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165 Pre-Cooling Strategies for the Refueling of Hydrogen Cylinders in Vehicular Transport

Authors: C. Hall, J. Ramos, V. Ramasamy

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Hydrocarbon-based fuel vehicles are a major contributor to air pollution due to harmful emissions produced, leading to a demand for cleaner fuel types. A leader in this pursuit is hydrogen, with its application in vehicles producing zero harmful emissions and the only by-product being water. To compete with the performance of conventional vehicles, hydrogen gas must be stored on-board of vehicles in cylinders at high pressures (35–70 MPa) and have a short refueling duration (approximately 3 mins). However, the fast-filling of hydrogen cylinders causes a significant rise in temperature due to the combination of the negative Joule-Thompson effect and the compression of the gas. This can lead to structural failure and therefore, a maximum allowable internal temperature of 85°C has been imposed by the International Standards Organization. The technological solution to tackle the issue of rapid temperature rise during the refueling process is to decrease the temperature of the gas entering the cylinder. Pre-cooling of the gas uses a heat exchanger and requires energy for its operation. Thus, it is imperative to determine the least amount of energy input that is required to lower the gas temperature for cost savings. A validated universal thermodynamic model is used to identify an energy-efficient pre-cooling strategy. The model requires negligible computational time and is applied to previously validated experimental cases to optimize pre-cooling requirements. The pre-cooling characteristics include the location within the refueling timeline and its duration. A constant pressure-ramp rate is imposed to eliminate the effects of rapid changes in mass flow rate. A pre-cooled gas temperature of -40°C is applied, which is the lowest allowable temperature. The heat exchanger is assumed to be ideal with no energy losses. The refueling of the cylinders is modeled with the pre-cooling split in ten percent time intervals. Furthermore, varying burst durations are applied in both the early and late stages of the refueling procedure. The model shows that pre-cooling in the later stages of the refuelling process is more energy-efficient than early pre-cooling. In addition, the efficiency of pre-cooling towards the end of the refueling process is independent of the pressure profile at the inlet. This leads to the hypothesis that pre-cooled gas should be applied as late as possible in the refueling timeline and at very low temperatures. The model had shown a 31% reduction in energy demand whilst achieving the same final gas temperature for a refueling scenario when pre-cooling was applied towards the end of the process. The identification of the most energy-efficient refueling approaches whilst adhering to the safety guidelines is imperative to reducing the operating cost of hydrogen refueling stations. Heat exchangers are energy-intensive and thus, reducing the energy requirement would lead to cost reduction. This investigation shows that pre-cooling should be applied as late as possible and for short durations.

Keywords: cylinder, hydrogen, pre-cooling, refueling, thermodynamic model

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164 Exploring the Motivations That Drive Paper Use in Clinical Practice Post-Electronic Health Record Adoption: A Nursing Perspective

Authors: Sinead Impey, Gaye Stephens, Lucy Hederman, Declan O'Sullivan

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Continued paper use in the clinical area post-Electronic Health Record (EHR) adoption is regularly linked to hardware and software usability challenges. Although paper is used as a workaround to circumvent challenges, including limited availability of a computer, this perspective does not consider the important role paper, such as the nurses’ handover sheet, play in practice. The purpose of this study is to confirm the hypothesis that paper use post-EHR adoption continues as paper provides both a cognitive tool (that assists with workflow) and a compensation tool (to circumvent usability challenges). Distinguishing the different motivations for continued paper-use could assist future evaluations of electronic record systems. Methods: Qualitative data were collected from three clinical care environments (ICU, general ward and specialist day-care) who used an electronic record for at least 12 months. Data were collected through semi-structured interviews with 22 nurses. Data were transcribed, themes extracted using an inductive bottom-up coding approach and a thematic index constructed. Findings: All nurses interviewed continued to use paper post-EHR adoption. While two distinct motivations for paper use post-EHR adoption were confirmed by the data - paper as a cognitive tool and paper as a compensation tool - further finding was that there was an overlap between the two uses. That is, paper used as a compensation tool could also be adapted to function as a cognitive aid due to its nature (easy to access and annotate) or vice versa. Rather than present paper persistence as having two distinctive motivations, it is more useful to describe it as presenting on a continuum with compensation tool and cognitive tool at either pole. Paper as a cognitive tool referred to pages such as nurses’ handover sheet. These did not form part of the patient’s record, although information could be transcribed from one to the other. Findings suggest that although the patient record was digitised, handover sheets did not fall within this remit. These personal pages continued to be useful post-EHR adoption for capturing personal notes or patient information and so continued to be incorporated into the nurses’ work. Comparatively, the paper used as a compensation tool, such as pre-printed care plans which were stored in the patient's record, appears to have been instigated in reaction to usability challenges. In these instances, it is expected that paper use could reduce or cease when the underlying problem is addressed. There is a danger that as paper affords nurses a temporary information platform that is mobile, easy to access and annotate, its use could become embedded in clinical practice. Conclusion: Paper presents a utility to nursing, either as a cognitive or compensation tool or combination of both. By fully understanding its utility and nuances, organisations can avoid evaluating all incidences of paper use (post-EHR adoption) as arising from usability challenges. Instead, suitable remedies for paper-persistence can be targeted at the root cause.

Keywords: cognitive tool, compensation tool, electronic record, handover sheet, nurse, paper persistence

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163 Assessing Acute Toxicity and Endocrine Disruption Potential of Selected Packages Internal Layers Extracts

Authors: N. Szczepanska, B. Kudlak, G. Yotova, S. Tsakovski, J. Namiesnik

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In the scientific literature related to the widely understood issue of packaging materials designed to have contact with food (food contact materials), there is much information on raw materials used for their production, as well as their physiochemical properties, types, and parameters. However, not much attention is given to the issues concerning migration of toxic substances from packaging and its actual influence on the health of the final consumer, even though health protection and food safety are the priority tasks. The goal of this study was to estimate the impact of particular foodstuff packaging type, food production, and storage conditions on the degree of leaching of potentially toxic compounds and endocrine disruptors to foodstuffs using the acute toxicity test Microtox and XenoScreen YES YAS assay. The selected foodstuff packaging materials were metal cans used for fish storage and tetrapak. Five stimulants respectful to specific kinds of food were chosen in order to assess global migration: distilled water for aqueous foods with a pH above 4.5; acetic acid at 3% in distilled water for acidic aqueous food with pH below 4.5; ethanol at 5% for any food that may contain alcohol; dimethyl sulfoxide (DMSO) and artificial saliva were used in regard to the possibility of using it as an simulation medium. For each packaging three independent variables (temperature and contact time) factorial design simulant was performed. Xenobiotics migration from epoxy resins was studied at three different temperatures (25°C, 65°C, and 121°C) and extraction time of 12h, 48h and 2 weeks. Such experimental design leads to 9 experiments for each food simulant as conditions for each experiment are obtained by combination of temperature and contact time levels. Each experiment was run in triplicate for acute toxicity and in duplicate for estrogen disruption potential determination. Multi-factor analysis of variation (MANOVA) was used to evaluate the effects of the three main factors solvent, temperature (temperature regime for cup), contact time and their interactions on the respected dependent variable (acute toxicity or estrogen disruption potential). From all stimulants studied the most toxic were can and tetrapak lining acetic acid extracts that are indication for significant migration of toxic compounds. This migration increased with increase of contact time and temperature and justified the hypothesis that food products with low pH values cause significant damage internal resin filling. Can lining extracts of all simulation medias excluding distilled water and artificial saliva proved to contain androgen agonists even at 25°C and extraction time of 12h. For tetrapak extracts significant endocrine potential for acetic acid, DMSO and saliva were detected.

Keywords: food packaging, extraction, migration, toxicity, biotest

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162 The Effects of the New Silk Road Initiatives and the Eurasian Union to the East-Central-Europe’s East Opening Policies

Authors: Tamas Dani

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The author’s research explores the geo-economical role and importance of some small and medium sized states, reviews their adaption strategies in foreign trade and also in foreign affairs in the course of changing into a multipolar world, uses international background. With these, the paper analyses the recent years and the future of ‘Opening towards Eastern foreign economic policies’ from East-Central Europe and parallel with that the ‘Western foreign economy policies’ from Asia, as the Chinese One Belt One Road new silk route plans (so far its huge part is an infrastructural development plan to reach international trade and investment aims). It can be today’s question whether these ideas will reshape the global trade or not. How does the new silk road initiatives and the Eurasian Union reflect the effect of globalization? It is worth to analyse that how did Central and Eastern European countries open to Asia; why does China have the focus of the opening policies in many countries and why could China be seen as the ‘winner’ of the world economic crisis after 2008. The research is based on the following methodologies: national and international literature, policy documents and related design documents, complemented by processing of international databases, statistics and live interviews with leaders from East-Central European countries’ companies and public administration, diplomats and international traders. The results also illustrated by mapping and graphs. The research will find out as major findings whether the state decision-makers have enough margin for manoeuvres to strengthen foreign economic relations. This work has a hypothesis that countries in East-Central Europe have real chance to diversify their relations in foreign trade, focus beyond their traditional partners. This essay focuses on the opportunities of East-Central-European countries in diversification of foreign trade relations towards China and Russia in terms of ‘Eastern Openings’. The effects of the new silk road initiatives and the Eurasian Union to Hungary’s economy with a comparing outlook on East-Central European countries and exploring common regional cooperation opportunities in this area. The essay concentrate on the changing trade relations between East-Central-Europe and China as well as Russia, try to analyse the effects of the new silk road initiatives and the Eurasian Union also. In the conclusion part, it shows how the cooperation is necessary for the East-Central European countries if they want to have a non-asymmetric trade with Russia, China or some Chinese regions (Pearl River Delta, Hainan, …). The form of the cooperation for the East-Central European nations can be Visegrad 4 Cooperation (V4), Central and Eastern European Countries (CEEC16), 3 SEAS Cooperation (or BABS – Baltic, Adriatic, Black Seas Initiative).

Keywords: China, East-Central Europe, foreign trade relations, geoeconomics, geopolitics, Russia

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161 Predicting and Obtaining New Solvates of Curcumin, Demethoxycurcumin and Bisdemethoxycurcumin Based on the Ccdc Statistical Tools and Hansen Solubility Parameters

Authors: J. Ticona Chambi, E. A. De Almeida, C. A. Andrade Raymundo Gaiotto, A. M. Do Espírito Santo, L. Infantes, S. L. Cuffini

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The solubility of active pharmaceutical ingredients (APIs) is challenging for the pharmaceutical industry. The new multicomponent crystalline forms as cocrystal and solvates present an opportunity to improve the solubility of APIs. Commonly, the procedure to obtain multicomponent crystalline forms of a drug starts by screening the drug molecule with the different coformers/solvents. However, it is necessary to develop methods to obtain multicomponent forms in an efficient way and with the least possible environmental impact. The Hansen Solubility Parameters (HSPs) is considered a tool to obtain theoretical knowledge of the solubility of the target compound in the chosen solvent. H-Bond Propensity (HBP), Molecular Complementarity (MC), Coordination Values (CV) are tools used for statistical prediction of cocrystals developed by the Cambridge Crystallographic Data Center (CCDC). The HSPs and the CCDC tools are based on inter- and intra-molecular interactions. The curcumin (Cur), target molecule, is commonly used as an anti‐inflammatory. The demethoxycurcumin (Demcur) and bisdemethoxycurcumin (Bisdcur) are natural analogues of Cur from turmeric. Those target molecules have differences in their solubilities. In this way, the work aimed to analyze and compare different tools for multicomponent forms prediction (solvates) of Cur, Demcur and Biscur. The HSP values were calculated for Cur, Demcur, and Biscur using the chemical group contribution methods and the statistical optimization from experimental data. The HSPmol software was used. From the HSPs of the target molecules and fifty solvents (listed in the HSP books), the relative energy difference (RED) was determined. The probability of the target molecules would be interacting with the solvent molecule was determined using the CCDC tools. A dataset of fifty molecules of different organic solvents was ranked for each prediction method and by a consensus ranking of different combinations: HSP, CV, HBP and MC values. Based on the prediction, 15 solvents were selected as Dimethyl Sulfoxide (DMSO), Tetrahydrofuran (THF), Acetonitrile (ACN), 1,4-Dioxane (DOX) and others. In a starting analysis, the slow evaporation technique from 50°C at room temperature and 4°C was used to obtain solvates. The single crystals were collected by using a Bruker D8 Venture diffractometer, detector Photon100. The data processing and crystal structure determination were performed using APEX3 and Olex2-1.5 software. According to the results, the HSPs (theoretical and optimized) and the Hansen solubility sphere for Cur, Demcur and Biscur were obtained. With respect to prediction analyses, a way to evaluate the predicting method was through the ranking and the consensus ranking position of solvates already reported in the literature. It was observed that the combination of HSP-CV obtained the best results when compared to the other methods. Furthermore, as a result of solvent selected, six new solvates, Cur-DOX, Cur-DMSO, Bicur-DOX, Bircur-THF, Demcur-DOX, Demcur-ACN and a new Biscur hydrate, were obtained. Crystal structures were determined for Cur-DOX, Biscur-DOX, Demcur-DOX and Bicur-Water. Moreover, the unit-cell parameter information for Cur-DMSO, Biscur-THF and Demcur-ACN were obtained. The preliminary results showed that the prediction method is showing a promising strategy to evaluate the possibility of forming multicomponent. It is currently working on obtaining multicomponent single crystals.

Keywords: curcumin, HSPs, prediction, solvates, solubility

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