Search results for: soluble tumor necrosis factor-like weak inducer of apoptosis
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Search results for: soluble tumor necrosis factor-like weak inducer of apoptosis

112 Internal Concept of Integrated Health by Agrarian Society in Malagasy Highlands for the Last Century

Authors: O. R. Razanakoto, L. Temple

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Living in a least developed country, the Malagasy society has a weak capacity to internalize progress, including health concerns. Since the arrival in the fifteenth century of Arabic script, called Sorabe, that was mainly dedicated to the aristocracy, until the colonial era beginning at the end of the nineteenth century and that has popularized the current usual script of the occidental civilization, the upcoming manuscripts that deal with apparent scientific or at least academic issue have been slowly established. So that, the Malagasy communities’ way of life is not well documented yet to allow a precise understanding of the major concerns, reason, and purpose of the existence of the farmers that compose them. A question arises, according to literature, how does Malagasy community that is dominated by agrarian society conceive the conservation of its wellbeing? This study aims to emphasize the scope and the limits of the « One Health » concept or of the Health Integrated Approach (HIA) that evolves at global scale, with regard to the specific context of local Malagasy smallholder farms. It is expected to identify how this society represents linked risks and the mechanisms between human health, animal health, plant health, and ecosystem health within the last 100 years. To do so, the framework to conduct systematic review for agricultural research has been deployed to access available literature. This task has been coupled with the reading of articles that are not indexed by online scientific search engine but that mention part of a history of agriculture and of farmers in Madagascar. This literature review has informed the interactions between human illnesses and those affecting animals and plants (breeded or wild) with any unexpected event (ecological or economic) that has modified the equilibrium of the ecosystem, or that has disturbed the livelihoods of agrarian communities. Besides, drivers that may either accentuate or attenuate the devasting effects of these illnesses and changes were revealed. The study has established that the reasons of human worries are not only physiological. Among the factors that regulate global health, food system and contemporary medicine have helped to the improvement of life expectancy from 55 to 63 years in Madagascar during the last 50 years. However, threats to global health are still occurring. New human or animal illnesses and livestock / plant pathology or enemies may also appear, whereas ancient illnesses that are supposed to have disappeared may be back. This study has highlighted how much important are the risks associated to the impact of unmanaged externalities that weaken community’s life. Many risks, and also solutions, come from abroad and have long term effects even though those happen as punctual event. Thus, a constructivist strategy is suggested to the « One Health » global concept throughout the record of local facts. This approach should facilitate the exploration of methodological pathways and the identification of relevant indicators for research related to HIA.

Keywords: agrarian system, health integrated approach, history, madagascar, resilience, risk

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111 Toward Understanding the Glucocorticoid Receptor Network in Cancer

Authors: Swati Srivastava, Mattia Lauriola, Yuval Gilad, Adi Kimchi, Yosef Yarden

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The glucocorticoid receptor (GR) has been proposed to play important, but incompletely understood roles in cancer. Glucocorticoids (GCs) are widely used as co-medication of various carcinomas, due to their ability to reduce the toxicity of chemotherapy. Furthermore, GR antagonism has proven to be a strategy to treat triple negative breast cancer and castration-resistant prostate cancer. These observations suggest differential GR involvement in cancer subtypes. The goal of our study has been to elaborate the current understanding of GR signaling in tumor progression and metastasis. Our study involves two cellular models, non-tumorigenic breast epithelial cells (MCF10A) and Ewing sarcoma cells (CHLA9). In our breast cell model, the results indicated that the GR agonist dexamethasone inhibits EGF-induced mammary cell migration, and this effect was blocked when cells were stimulated with a GR antagonist, namely RU486. Microarray analysis for gene expression revealed that the mechanism underlying inhibition involves dexamenthasone-mediated repression of well-known activators of EGFR signaling, alongside with enhancement of several EGFR’s negative feedback loops. Because GR mainly acts primarily through composite response elements (GREs), or via a tethering mechanism, our next aim has been to find the transcription factors (TFs) which can interact with GR in MCF10A cells.The TF-binding motif overrepresented at the promoter of dexamethasone-regulated genes was predicted by using bioinformatics. To validate the prediction, we performed high-throughput Protein Complementation Assays (PCA). For this, we utilized the Gaussia Luciferase PCA strategy, which enabled analysis of protein-protein interactions between GR and predicted TFs of mammary cells. A library comprising both nuclear receptors (estrogen receptor, mineralocorticoid receptor, GR) and TFs was fused to fragments of GLuc, namely GLuc(1)-X, X-GLuc(1), and X-GLuc(2), where GLuc(1) and GLuc(2) correspond to the N-terminal and C-terminal fragments of the luciferase gene.The resulting library was screened, in human embryonic kidney 293T (HEK293T) cells, for all possible interactions between nuclear receptors and TFs. By screening all of the combinations between TFs and nuclear receptors, we identified several positive interactions, which were strengthened in response to dexamethasone and abolished in response to RU486. Furthermore, the interactions between GR and the candidate TFs were validated by co-immunoprecipitation in MCF10A and in CHLA9 cells. Currently, the roles played by the uncovered interactions are being evaluated in various cellular processes, such as cellular proliferation, migration, and invasion. In conclusion, our assay provides an unbiased network analysis between nuclear receptors and other TFs, which can lead to important insights into transcriptional regulation by nuclear receptors in various diseases, in this case of cancer.

Keywords: epidermal growth factor, glucocorticoid receptor, protein complementation assay, transcription factor

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110 Rheological Characterization of Polysaccharide Extracted from Camelina Meal as a New Source of Thickening Agent

Authors: Mohammad Anvari, Helen S. Joyner (Melito)

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Camelina sativa (L.) Crantz is an oilseed crop currently used for the production of biofuels. However, the low price of diesel and gasoline has made camelina an unprofitable crop for farmers, leading to declining camelina production in the US. Hence, the ability to utilize camelina byproduct (defatted meal) after oil extraction would be a pivotal factor for promoting the economic value of the plant. Camelina defatted meal is rich in proteins and polysaccharides. The great diversity in the polysaccharide structural features provides a unique opportunity for use in food formulations as thickeners, gelling agents, emulsifiers, and stabilizers. There is currently a great degree of interest in the study of novel plant polysaccharides, as they can be derived from readily accessible sources and have potential application in a wide range of food formulations. However, there are no published studies on the polysaccharide extracted from camelina meal, and its potential industrial applications remain largely underexploited. Rheological properties are a key functional feature of polysaccharides and are highly dependent on the material composition and molecular structure. Therefore, the objective of this study was to evaluate the rheological properties of the polysaccharide extracted from camelina meal at different conditions to obtain insight on the molecular characteristics of the polysaccharide. Flow and dynamic mechanical behaviors were determined under different temperatures (5-50°C) and concentrations (1-6% w/v). Additionally, the zeta potential of the polysaccharide dispersion was measured at different pHs (2-11) and a biopolymer concentration of 0.05% (w/v). Shear rate sweep data revealed that the camelina polysaccharide displayed shear thinning (pseudoplastic) behavior, which is typical of polymer systems. The polysaccharide dispersion (1% w/v) showed no significant changes in viscosity with temperature, which makes it a promising ingredient in products requiring texture stability over a range of temperatures. However, the viscosity increased significantly with increased concentration, indicating that camelina polysaccharide can be used in food products at different concentrations to produce a range of textures. Dynamic mechanical spectra showed similar trends. The temperature had little effect on viscoelastic moduli. However, moduli were strongly affected by concentration: samples exhibited concentrated solution behavior at low concentrations (1-2% w/v) and weak gel behavior at higher concentrations (4-6% w/v). These rheological properties can be used for designing and modeling of liquid and semisolid products. Zeta potential affects the intensity of molecular interactions and molecular conformation and can alter solubility, stability, and eventually, the functionality of the materials as their environment changes. In this study, the zeta potential value significantly decreased from 0.0 to -62.5 as pH increased from 2 to 11, indicating that pH may affect the functional properties of the polysaccharide. The results obtained in the current study showed that camelina polysaccharide has significant potential for application in various food systems and can be introduced as a novel anionic thickening agent with unique properties.

Keywords: Camelina meal, polysaccharide, rheology, zeta potential

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109 The Link between Strategic Sense-Making and Performance in Dubai Public Sector

Authors: Mohammad Rahman, Guy Burton, Megan Mathias

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Strategic management as an organizational practice was adopted by the public sector in the New Public Management (NPM) era that began in most parts of the world in the 1980s. Strategy as a new public management concept was subscribed by governments in both developed and developing world, as they were persuaded that clearly defined vision, mission and goals, as well as programs and projects - aligned with the goals - could potentially help achieve government vision at the national level and organizational goals at the service-delivery level. The advocates for strategic management in the public sector saw an inherent link between strategy and performance, claiming that the implementation of organizational strategy has an effect on the overall performance of an organization. Arguably, many government entities that have failed in enhancing team and individual performance had poorly-designed strategy or weak strategy implementation. Another key argument about low-level performance is linked with lack of strategic sense-making and orientation by middle managers in particular. Scholars maintain that employees at all levels need to understand strategic management plan in order to facilitate its implementation. Therefore, involving employees (particularly the middle managers) from the beginning potentially helps an organization avoid the drop in performance, and on the contrary would increase their commitment. The United Arab Emirates (UAE) is well known for adopting public sector reform strategies and tools since the 1990s. This observation is contextually pertinent in the case of the Government of Dubai, which has provided a Strategy Execution Guide to all of its entities to achieve high level strategic success in service delivery. The Dubai public sector also adopts road maps for e-Government, Smart Dubai, Expo 2020, investment, environment, education, health and other sectors. Evidently, some of these strategies are bringing tangible (e.g. Smart Dubai transformation) results in a transformational manner. However, the amount of academic research and literature on the strategy process vis-à-vis staff performance in the Government of Dubai is limited. In this backdrop, this study examines how individual performance of public sector employees in Dubai is linked with their sense-making, engagement and orientation with strategy development and implementation processes. Based on a theoretical framework, this study will undertake a sample-based questionnaire survey amongst middle managers in Dubai public sector to (a) measure the level of engagement of middle managers in strategy development and implementation processes as perceived by them; (b) observe the organizational landscape in which role expectations are placed on middle managers; and (c) examine the impact of employee engagement in strategy development process and the conditions for role expectations on individual performance. The paper is expected to provide new insights on the interface between strategic sense-making and performance in order to contribute a better understanding of the current culture/practices of staff engagement in strategic management in the public sector of Dubai.

Keywords: employee performance, government of Dubai, middle managers, strategic sense-making

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108 Positron Emission Tomography Parameters as Predictors of Pathologic Response and Nodal Clearance in Patients with Stage IIIA NSCLC Receiving Trimodality Therapy

Authors: Andrea L. Arnett, Ann T. Packard, Yolanda I. Garces, Kenneth W. Merrell

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Objective: Pathologic response following neoadjuvant chemoradiation (CRT) has been associated with improved overall survival (OS). Conflicting results have been reported regarding the pathologic predictive value of positron emission tomography (PET) response in patients with stage III lung cancer. The aim of this study was to evaluate the correlation between post-treatment PET response and pathologic response utilizing novel FDG-PET parameters. Methods: This retrospective study included patients with non-metastatic, stage IIIA (N2) NSCLC cancer treated with CRT followed by resection. All patients underwent PET prior to and after neoadjuvant CRT. Univariate analysis was utilized to assess correlations between PET response, nodal clearance, pCR, and near-complete pathologic response (defined as the microscopic residual disease or less). Maximal standard uptake value (SUV), standard uptake ratio (SUR) [normalized independently to the liver (SUR-L) and blood pool (SUR-BP)], metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured pre- and post-chemoradiation. Results: A total of 44 patients were included for review. Median age was 61.9 years, and median follow-up was 2.6 years. Histologic subtypes included adenocarcinoma (72.2%) and squamous cell carcinoma (22.7%), and the majority of patients had the T2 disease (59.1%). The rate of pCR and near-complete pathologic response within the primary lesion was 28.9% and 44.4%, respectively. The average reduction in SUVmₐₓ was 9.2 units (range -1.9-32.8), and the majority of patients demonstrated some degree of favorable treatment response. SUR-BP and SUR-L showed a mean reduction of 4.7 units (range -0.1-17.3) and 3.5 units (range –1.7-12.6), respectively. Variation in PET response was not significantly associated with histologic subtype, concurrent chemotherapy type, stage, or radiation dose. No significant correlation was found between pathologic response and absolute change in MTV or TLG. Reduction in SUVmₐₓ and SUR were associated with increased rate of pathologic response (p ≤ 0.02). This correlation was not impacted by normalization of SUR to liver versus mediastinal blood pool. A threshold of > 75% decrease in SUR-L correlated with near-complete response, with a sensitivity of 57.9% and specificity of 85.7%, as well as positive and negative predictive values of 78.6% and 69.2%, respectively (diagnostic odds ratio [DOR]: 5.6, p=0.02). A threshold of >50% decrease in SUR was also significantly associated pathologic response (DOR 12.9, p=0.2), but specificity was substantially lower when utilizing this threshold value. No significant association was found between nodal PET parameters and pathologic nodal clearance. Conclusions: Our results suggest that treatment response to neoadjuvant therapy as assessed on PET imaging can be a predictor of pathologic response when evaluated via SUV and SUR. SUR parameters were associated with higher diagnostic odds ratios, suggesting improved predictive utility compared to SUVmₐₓ. MTV and TLG did not prove to be significant predictors of pathologic response but may warrant further investigation in a larger cohort of patients.

Keywords: lung cancer, positron emission tomography (PET), standard uptake ratio (SUR), standard uptake value (SUV)

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107 Removal of Heavy Metals by Ultrafiltration Assisted with Chitosan or Carboxy-Methyl Cellulose

Authors: Boukary Lam, Sebastien Deon, Patrick Fievet, Nadia Crini, Gregorio Crini

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Treatment of heavy metal-contaminated industrial wastewater has become a major challenge over the last decades. Conventional processes for the treatment of metal-containing effluents do not always simultaneously satisfy both legislative and economic criteria. In this context, coupling of processes can then be a promising alternative to the conventional approaches used by industry. The polymer-assisted ultrafiltration (PAUF) process is one of these coupling processes. Its principle is based on a sequence of steps with reaction (e.g., complexation) between metal ions and a polymer and a step involving the rejection of the formed species by means of a UF membrane. Unlike free ions, which can cross the UF membrane due to their small size, the polymer/ion species, the size of which is larger than pore size, are rejected. The PAUF process was deeply investigated herein in the case of removal of nickel ions by adding chitosan and carboxymethyl cellulose (CMC). Experiments were conducted with synthetic solutions containing 1 to 100 ppm of nickel ions with or without the presence of NaCl (0.05 to 0.2 M), and an industrial discharge water (containing several metal ions) with and without polymer. Chitosan with a molecular weight of 1.8×105 g mol⁻¹ and a degree of acetylation close to 15% was used. CMC with a degree of substitution of 0.7 and a molecular weight of 9×105 g mol⁻¹ was employed. Filtration experiments were performed under cross-flow conditions with a filtration cell equipped with a polyamide thin film composite flat-sheet membrane (3.5 kDa). Without the step of polymer addition, it was found that nickel rejection decreases from 80 to 0% with increasing metal ion concentration and salt concentration. This behavior agrees qualitatively with the Donnan exclusion principle: the increase in the electrolyte concentration screens the electrostatic interaction between ions and the membrane fixed the charge, which decreases their rejection. It was shown that addition of a sufficient amount of polymer (greater than 10⁻² M of monomer unit) can offset this decrease and allow good metal removal. However, the permeation flux was found to be somewhat reduced due to the increase in osmotic pressure and viscosity. It was also highlighted that the increase in pH (from 3 to 9) has a strong influence on removal performances: the higher pH value, the better removal performance. The two polymers have shown similar performance enhancement at natural pH. However, chitosan has proved more efficient in slightly basic conditions (above its pKa) whereas CMC has demonstrated very weak rejection performances when pH is below its pKa. In terms of metal rejection, chitosan is thus probably the better option for basic or strongly acid (pH < 4) conditions. Nevertheless, CMC should probably be preferred to chitosan in natural conditions (5 < pH < 8) since its impact on the permeation flux is less significant. Finally, ultrafiltration of an industrial discharge water has shown that the increase in metal ion rejection induced by the polymer addition is very low due to the competing phenomenon between the various ions present in the complex mixture.

Keywords: carboxymethyl cellulose, chitosan, heavy metals, nickel ion, polymer-assisted ultrafiltration

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106 Antibacterial Activity of Rosmarinus officinalis (Rosemary) and Murraya koenigii (Curry Leaves) against Multidrug Resistant S. aureus and Coagulase Negative Staphylococcus Species

Authors: Asma Naim, Warda Mushtaq

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Staphylococcus species are the most versatile and adaptive organism. They are widespread and naturally found on the skin, mucosa and nose in humans. Among these, Staphylococcus aureus is the most important species. These organisms act as opportunistic pathogens and can infect various organs of the host, causing minor skin infection to severe toxin mediated diseases, and life threatening nosocomial infections. Staphylococcus aureus has acquired resistance against β-lactam antibiotics by the production of β-lactamase, and Methicillin-Resistant Staphylococcus aureus (MRSA) strains have also been reported with increasing frequency. MRSA strains have been associated with nosocomial as well as community acquired infections. Medicinal plants have enormous potential as antimicrobial substances and have been used in traditional medicine. Search for medicinally valuable plants with antimicrobial activity is being emphasized due to increasing antibiotic resistance in bacteria. In the present study, the antibacterial potential of Rosmarinus officinalis (Rosemary) and Murraya koenigii (curry leaves) was evaluated. These are common household herbs used in food as enhancer of flavor and aroma. The crude aqueous infusion, decoction and ethanolic extracts of curry leaves and rosemary and essential oil of rosemary were investigated in the present study for antibacterial activity against multi-drug resistant Staphylococcus strains using well diffusion method. In the present study, 60 Multi-drug resistant clinical isolates of S. aureus (43) and Coagulase Negative Staphylococci (CoNS) (17) were screened against different concentrations of crude extracts of Rosmarinus officinalis and Murraya koenigii. Out of these 60 isolates, 43 were sensitive to the aqueous infusion of rosemary; 23 to aqueous decoction and 58 to ethanolic extract whereas, 24 isolates were sensitive to the essential oil. In the case of the curry leaves, no antibacterial activity was observed in aqueous infusion and decoction while only 14 isolates were sensitive to the ethanolic extract. The aqueous infusion of rosemary (50% concentration) exhibited a zone of inhibition of 21(±5.69) mm. against CoNS and 17(±4.77) mm. against S. aureus, the zone of inhibition of 50% concentration of aqueous decoction of rosemary was also larger against CoNS 17(±5.78) mm. then S. aureus 13(±6.91) mm. and the 50% concentrated ethanolic extract showed almost similar zone of inhibition in S. aureus 22(±3.61) mm. and CoNS 21(±7.64) mm. whereas, the essential oil of rosemary showed greater zone of inhibition against S. aureus i.e., 16(±4.67) mm. while CoNS showed 15(±6.94) mm. These results show that ethanolic extract of rosemary has significant antibacterial activity. Aqueous infusion and decoction of curry leaves revealed no significant antibacterial potential against all Staphylococcal species and ethanolic extract also showed only a weak response. Staphylococcus strains were susceptible to crude extracts and essential oil of rosemary in a dose depend manner, where the aqueous infusion showed highest zone of inhibition and ethanolic extract also demonstrated antistaphylococcal activity. These results demonstrate that rosemary possesses antistaphylococcal activity.

Keywords: antibacterial activity, curry leaves, multidrug resistant, rosemary, S. aureus

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105 Comparison of Cu Nanoparticle Formation and Properties with and without Surrounding Dielectric

Authors: P. Dubcek, B. Pivac, J. Dasovic, V. Janicki, S. Bernstorff

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When grown only to nanometric sizes, metallic particles (e.g. Ag, Au and Cu) exhibit specific optical properties caused by the presence of plasmon band. The plasmon band represents collective oscillation of the conduction electrons, and causes a narrow band absorption of light in the visible range. When the nanoparticles are embedded in a dielectric, they also cause modifications of dielectrics optical properties. This can be fine-tuned by tuning the particle size. We investigated Cu nanoparticle growth with and without surrounding dielectric (SiO2 capping layer). The morphology and crystallinity were investigated by GISAXS and GIWAXS, respectively. Samples were produced by high vacuum thermal evaporation of Cu onto monocrystalline silicon substrate held at room temperature, 100°C or 180°C. One series was in situ capped by 10nm SiO2 layer. Additionally, samples were annealed at different temperatures up to 550°C, also in high vacuum. The room temperature deposited samples annealed at lower temperatures exhibit continuous film structure: strong oscillations in the GISAXS intensity are present especially in the capped samples. At higher temperatures enhanced surface dewetting and Cu nanoparticles (nanoislands) formation partially destroy the flatness of the interface. Therefore the particle type of scattering is enhanced, while the film fringes are depleted. However, capping layer hinders particle formation, and continuous film structure is preserved up to higher annealing temperatures (visible as strong and persistent fringes in GISAXS), compared to the non- capped samples. According to GISAXS, lateral particle sizes are reduced at higher temperatures, while particle height is increasing. This is ascribed to close packing of the formed particles at lower temperatures, and GISAXS deduced sizes are partially the result of the particle agglomerate dimensions. Lateral maxima in GISAXS are an indication of good positional correlation, and the particle to particle distance is increased as the particles grow with temperature elevation. This coordination is much stronger in the capped and lower temperature deposited samples. The dewetting is much more vigorous in the non-capped sample, and since nanoparticles are formed in a range of sizes, correlation is receding both with deposition and annealing temperature. Surface topology was checked by atomic force microscopy (AFM). Capped sample's surfaces were smoother and lateral size of the surface features were larger compared to the non-capped samples. Altogether, AFM results suggest somewhat larger particles and wider size distribution, and this can be attributed to the difference in probe size. Finally, the plasmonic effect was monitored by UV-Vis reflectance spectroscopy, and relative weak plasmonic effect could be explained by uncomplete dewetting or partial interconnection of the formed particles.

Keywords: coper, GISAXS, nanoparticles, plasmonics

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104 Improving Efficiency of Organizational Performance: The Role of Human Resources in Supply Chains and Job Rotation Practice

Authors: Moh'd Anwer Al-Shboul

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Jordan Customs (JC) has been established to achieve objectives that must be consistent with the guidance of the wise leadership and its aspirations toward tomorrow. Therefore, it has developed several needed tools to provide a distinguished service to simplify work procedures and used modern technologies. A supply chain (SC) consists of all parties that are involved directly or indirectly in order to fulfill a customer request, which includes manufacturers, suppliers, shippers, retailers and even customer brokers. Within each firm, the SC includes all functions involved in receiving a filling a customers’ requests; one of the main functions include customer service. JC and global SCs are evolving into dynamic environment, which requires flexibility, effective communication, and team management. Thus, human resources (HRs) insight in these areas are critical for the effective development of global process network. The importance of HRs has increased significantly due to the role of employees depends on their knowledge, competencies, abilities, skills, and motivations. Strategic planning in JC began at the end of the 1990’s including operational strategy for Human Resource Management and Development (HRM&D). However, a huge transformation in human resources happened at the end of 2006; new employees’ regulation for customs were prepared, approved and applied at the end of 2007. Therefore, many employees lost their positions, while others were selected based on professorial recruitment and selection process (enter new blood). One of several policies that were applied by human resources in JC department is job rotation. From the researcher’s point of view, it was not based on scientific basis to achieve its goals and objectives, which at the end leads to having a significant negative impact on the Organizational Performance (OP) and weak job rotation approach. The purpose of this study is to call attention to re-review the applying process and procedure of job rotation that HRM directorate is currently applied at JC. Furthermore, it presents an overview of managing the HRs in the SC network that affects their success. The research methodology employed in this study was described as qualitative by conducting few interviews with managers, internal employee, external clients and reviewing the related literature to collect some qualitative data from secondary sources. Thus, conducting frequently and unstructured job rotation policy (i.e. monthly) will have a significant negative impact on JC performance as a whole. The results of this study show that the main impacts will affect on three main elements in JC: (1) internal employees' performance; (2) external clients, who are dealing with customs services; and finally, JC performance as a whole. In order to implement a successful and perfect job rotation technique at JC in a scientific way and to achieve its goals and objectives; JCs should be taken into consideration the proposed solutions and recommendations that will be presented in this study.

Keywords: efficiency, supply chain, human resources, job rotation, organizational performance, Jordan customs

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103 Islam in Nation Building: Case Studies of Kazakhstan and Kyrgyzstan

Authors: Etibar Guliyev, Durdana Jafarli

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The breakdown of the Soviet Union in the early 1990s and the 9/11 attacks resulted in the global changes created a totally new geopolitical situation for the Muslim populated republics of the former Soviet Union. Located between great powers such as China and Russia, as well as theocratic states like Iran and Afghanistan, the newly independent Central Asian states were facing a dilemma to choose a new politico-ideological course for development. Policies dubbed Perestroyka and Glasnost leading to the collapse of the world’s once superpower brought about a considerable rise in the national and religious self-consciousness of the Muslim population of the USSR where the religion was prohibited under the strict communist rule. Moreover, the religious movements prohibited during the Soviet era acted as a part of national straggle to gain their freedom from Moscow. The policies adopted by the Central Asian countries to manage the religious revival and extremism in their countries vary dramatically from each other. As Kazakhstan and Kyrgyzstan are located between Russia and China and hosting a considerable number of the Russian population, these countries treated Islamic revival more tolerantly trying benefit from it in the nation-building process. The importance of the topic could be explained with the fact that it investigates an alternative way of management of religious activities and movements. The recent developments in the Middle East, Syria and Iraq in particular, and the fact that hundreds of fighters from the Central Asian republics joined the ISIL terrorist organization once again highlights the implications of the proper regulation of religious activities not only for domestic, but also for regional and global politics. The paper is based on multiple research methods. The process trace method was exploited to better understand the Russification and anti-religious policies to which the Central Asian countries were subject during the Soviet era. The comparative analyse method was also used to better understand the common and distinct features of the politics of religion of Kazakhstan and Kyrgyzstan and the rest of the Central Asian countries. Various legislation acts, as well as secondary sources were investigated to this end. Mostly constructivist approach and a theory suggesting that religion supports national identity when there is a third cohesion that threatens both and when elements of national identity are weak. Preliminary findings suggest that in line with policies aimed at gradual reduction of Russian influence, as well as in the face of ever-increasing migration from China, the mentioned countries incorporated some Islamic elements into domestic policies as a part and parcel of national culture. Kazakhstan and Kyrgyzstan did not suppress religious activities, which was case in neighboring states, but allowed in a controlled way Islamic movements to have a relatively freedom of action which in turn led to the less violent religious extremism further boosting national identity.

Keywords: identity, Islam, nationalism, terrorism

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102 The Brain’s Attenuation Coefficient as a Potential Estimator of Temperature Elevation during Intracranial High Intensity Focused Ultrasound Procedures

Authors: Daniel Dahis, Haim Azhari

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Noninvasive image-guided intracranial treatments using high intensity focused ultrasound (HIFU) are on the course of translation into clinical applications. They include, among others, tumor ablation, hyperthermia, and blood-brain-barrier (BBB) penetration. Since many of these procedures are associated with local temperature elevation, thermal monitoring is essential. MRI constitutes an imaging method with high spatial resolution and thermal mapping capacity. It is the currently leading modality for temperature guidance, commonly under the name MRgHIFU (magnetic-resonance guided HIFU). Nevertheless, MRI is a very expensive non-portable modality which jeopardizes its accessibility. Ultrasonic thermal monitoring, on the other hand, could provide a modular, cost-effective alternative with higher temporal resolution and accessibility. In order to assess the feasibility of ultrasonic brain thermal monitoring, this study investigated the usage of brain tissue attenuation coefficient (AC) temporal changes as potential estimators of thermal changes. Newton's law of cooling describes a temporal exponential decay behavior for the temperature of a heated object immersed in a relatively cold surrounding. Similarly, in the case of cerebral HIFU treatments, the temperature in the region of interest, i.e., focal zone, is suggested to follow the same law. Thus, it was hypothesized that the AC of the irradiated tissue may follow a temporal exponential behavior during cool down regime. Three ex-vivo bovine brain tissue specimens were inserted into plastic containers along with four thermocouple probes in each sample. The containers were placed inside a specially built ultrasonic tomograph and scanned at room temperature. The corresponding pixel-averaged AC was acquired for each specimen and used as a reference. Subsequently, the containers were placed in a beaker containing hot water and gradually heated to about 45ᵒC. They were then repeatedly rescanned during cool down using ultrasonic through-transmission raster trajectory until reaching about 30ᵒC. From the obtained images, the normalized AC and its temporal derivative as a function of temperature and time were registered. The results have demonstrated high correlation (R² > 0.92) between both the brain AC and its temporal derivative to temperature. This indicates the validity of the hypothesis and the possibility of obtaining brain tissue temperature estimation from the temporal AC thermal changes. It is important to note that each brain yielded different AC values and slopes. This implies that a calibration step is required for each specimen. Thus, for a practical acoustic monitoring of the brain, two steps are suggested. The first step consists of simply measuring the AC at normal body temperature. The second step entails measuring the AC after small temperature elevation. In face of the urging need for a more accessible thermal monitoring technique for brain treatments, the proposed methodology enables a cost-effective high temporal resolution acoustical temperature estimation during HIFU treatments.

Keywords: attenuation coefficient, brain, HIFU, image-guidance, temperature

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101 Evaluation of Kabul BRT Route Network with Application of Integrated Land-use and Transportation Model

Authors: Mustafa Mutahari, Nao Sugiki, Kojiro Matsuo

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The four decades of war, lack of job opportunities, poverty, lack of services, and natural disasters in different provinces of Afghanistan have contributed to a rapid increase in the population of Kabul, the capital city of Afghanistan. Population census has not been conducted since 1979, the first and last population census in Afghanistan. However, according to population estimations by Afghan authorities, the population of Kabul has been estimated at more than 4 million people, whereas the city was designed for two million people. Although the major transport mode of Kabul residents is public transport, responsible authorities within the country failed to supply the required means of transportation systems for the city. Besides, informal resettlement, lack of intersection control devices, presence of illegal vendors on streets, presence of illegal and unstandardized on-street parking and bus stops, driver`s unprofessional behavior, weak traffic law enforcement, and blocked roads and sidewalks have contributed to the extreme traffic congestion of Kabul. In 2018, the government of Afghanistan approved the Kabul city Urban Design Framework (KUDF), a vision towards the future of Kabul, which provides strategies and design guidance at different scales to direct urban development. Considering traffic congestion of the city and its budget limitations, the KUDF proposes a BRT route network with seven lines to reduce the traffic congestion, and it is said to facilitate more than 50% of Kabul population to benefit from this service. Based on the KUDF, it is planned to increase the BRT mode share from 0% to 17% and later to 30% in medium and long-term planning scenarios, respectively. Therefore, a detailed research study is needed to evaluate the proposed system before the implementation stage starts. The integrated land-use transport model is an effective tool to evaluate the Kabul BRT because of its future assessment capabilities that take into account the interaction between land use and transportation. This research aims to analyze and evaluate the proposed BRT route network with the application of an integrated land-use and transportation model. The research estimates the population distribution and travel behavior of Kabul within small boundary scales. The actual road network and land-use detailed data of the city are used to perform the analysis. The BRT corridors are evaluated not only considering its impacts on the spatial interactions in the city`s transportation system but also on the spatial developments. Therefore, the BRT are evaluated with the scenarios of improving the Kabul transportation system based on the distribution of land-use or spatial developments, planned development typology and population distribution of the city. The impacts of the new improved transport system on the BRT network are analyzed and the BRT network is evaluated accordingly. In addition, the research also focuses on the spatial accessibility of BRT stops, corridors, and BRT line beneficiaries, and each BRT stop and corridor are evaluated in terms of both access and geographic coverage, as well.

Keywords: accessibility, BRT, integrated land-use and transport model, travel behavior, spatial development

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100 An Early Intervention Framework for Supporting Students’ Mathematical Development in the Transition to University STEM Programmes

Authors: Richard Harrison

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Developing competency in mathematics and related critical thinking skills is essential to the education of undergraduate students of Science, Technology, Engineering and Mathematics (STEM). Recently, the HE sector has been impacted by a seemingly widening disconnect between the mathematical competency of incoming first-year STEM students and their entrance qualification tariffs. Despite relatively high grades in A-Level Mathematics, students may initially lack fundamental skills in key areas such as algebraic manipulation and have limited capacity to apply problem solving strategies. Compounded by compensatory measures applied to entrance qualifications during the pandemic, there has been an associated decline in student performance on introductory university mathematics modules. In the UK, a number of online resources have been developed to help scaffold the transition to university mathematics. However, in general, these do not offer a structured learning journey focused on individual developmental needs, nor do they offer an experience coherent with the teaching and learning characteristics of the destination institution. In order to address some of these issues, a bespoke framework has been designed and implemented on our VLE in the Faculty of Engineering & Physical Sciences (FEPS) at the University of Surrey. Called the FEPS Maths Support Framework, it was conceived to scaffold the mathematical development of individuals prior to entering the university and during the early stages of their transition to undergraduate studies. More than 90% of our incoming STEM students voluntarily participate in the process. Students complete a set of initial diagnostic questions in the late summer. Based on their performance and feedback on these questions, they are subsequently guided to self-select specific mathematical topic areas for review using our proprietary resources. This further assists students in preparing for discipline related diagnostic tests. The framework helps to identify students who are mathematically weak and facilitates early intervention to support students according to their specific developmental needs. This paper presents a summary of results from a rich data set captured from the framework over a 3-year period. Quantitative data provides evidence that students have engaged and developed during the process. This is further supported by process evaluation feedback from the students. Ranked performance data associated with seven key mathematical topic areas and eight engineering and science discipline areas reveals interesting patterns which can be used to identify more generic relative capabilities of the discipline area cohorts. In turn, this facilitates evidence based management of the mathematical development of the new cohort, informing any associated adjustments to teaching and learning at a more holistic level. Evidence is presented establishing our framework as an effective early intervention strategy for addressing the sector-wide issue of supporting the mathematical development of STEM students transitioning to HE

Keywords: competency, development, intervention, scaffolding

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99 Brazilian Brown Propolis as a Natural Source against Leishmania amazonensis

Authors: Victor Pena Ribeiro, Caroline Arruda, Jennyfer Andrea Aldana Mejia, Jairo Kenupp Bastos

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Leishmaniasis is a serious health problem around the world. The treatment of infected individuals with pentavalent antimonial drugs is the main therapeutic strategy. However, they present high toxicity and persistence side effects. Therefore, the discovery of new and safe natural-derived therapeutic agents against leishmaniasis is important. Propolis is a resin of viscous consistency produced by Apis mellifera bees from parts of plants. The main types of Brazilian propolis are green, red, yellow and brown. Thus, the aim of this work was to investigate the chemical composition and leishmanicidal properties of a brown propolis (BP). For this purpose, the hydroalcoholic crude extract of BP was obtained and was fractionated by liquid-liquid chromatography. The chemical profile of the extract and its fractions were obtained by HPLC-UV-DAD. The fractions were submitted to preparative HPLC chromatography for isolation of the major compounds of each fraction. They were analyzed by NMR for structural determination. The volatile compounds were obtained by hydrodistillation and identified by GC/MS. Promastigote forms of Leishmania amazonensis were cultivated in M199 medium and then 2×106 parasites.mL-1 were incubated in 96-well microtiter plates with the samples. The BP was dissolved in dimethyl sulfoxide (DMSO) and diluted into the medium, to give final concentrations of 1.56, 3.12, 6.25, 12.5, 25 and 50 µg.mL⁻¹. The plates were incubated at 25ºC for 24 h, and the lysis percentage was determined by using a Neubauer chamber. The bioassays were performed in triplicate, using a medium with 0.5% DMSO as a negative control and amphotericin B as a positive control. The leishimnicidal effect against promastigote forms was also evaluated at the same concentrations. Cytotoxicity experiments also were performed in 96-well plates against normal (CHO-k1) and tumor cell lines (AGP01 and HeLa) using XTT colorimetric method. Phenolic compounds, flavonoids, and terpenoids were identified in brown propolis. The major compounds were identified as follows: p-coumaric acid (24.6%) for a methanolic fraction, Artepelin-C (29.2%) for ethyl acetate fraction and the compounds of hexane fraction are in the process of structural elucidation. The major volatile compounds identified were β-caryophyllene (10.9%), germacrene D (9.7%), nerolidol (10.8%) and spathulenol (8.5%). The propolis did not show cytotoxicity against normal cell lines (CHO) with IC₅₀ > 100 μg.mL⁻¹, whereas the IC₅₀ < 10 μg.mL⁻¹ showed a potential against the AGP01 cell line, propolis did not demonstrate cytotoxicity against HeLa cell lines IC₅₀ > 100 μg.mL⁻¹. In the determination of the leishmanicidal activity, the highest (50 μg.mL⁻¹) and lowest (1.56 μg.mL⁻¹) concentrations of the crude extract caused the lysis of 76% and 45% of promastigote forms of L. amazonensis, respectively. To the amastigote form, the highest (50 μg.mL⁻¹) and lowest (1.56 μg.mL⁻¹) concentrations caused the mortality of 89% and 75% of L. amazonensis, respectively. The IC₅₀ was 2.8 μg.mL⁻¹ to amastigote form and 3.9 μg.mL⁻¹ to promastigote form, showing a promising activity against Leishmania amazonensis.

Keywords: amastigote, brown propolis, cytotoxicity, promastigote

Procedia PDF Downloads 135
98 Computational Approaches to Study Lineage Plasticity in Human Pancreatic Ductal Adenocarcinoma

Authors: Almudena Espin Perez, Tyler Risom, Carl Pelz, Isabel English, Robert M. Angelo, Rosalie Sears, Andrew J. Gentles

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Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly malignancies. The role of the tumor microenvironment (TME) is gaining significant attention in cancer research. Despite ongoing efforts, the nature of the interactions between tumors, immune cells, and stromal cells remains poorly understood. The cell-intrinsic properties that govern cell lineage plasticity in PDAC and extrinsic influences of immune populations require technically challenging approaches due to the inherently heterogeneous nature of PDAC. Understanding the cell lineage plasticity of PDAC will improve the development of novel strategies that could be translated to the clinic. Members of the team have demonstrated that the acquisition of ductal to neuroendocrine lineage plasticity in PDAC confers therapeutic resistance and is a biomarker of poor outcomes in patients. Our approach combines computational methods for deconvolving bulk transcriptomic cancer data using CIBERSORTx and high-throughput single-cell imaging using Multiplexed Ion Beam Imaging (MIBI) to study lineage plasticity in PDAC and its relationship to the infiltrating immune system. The CIBERSORTx algorithm uses signature matrices from immune cells and stroma from sorted and single-cell data in order to 1) infer the fractions of different immune cell types and stromal cells in bulked gene expression data and 2) impute a representative transcriptome profile for each cell type. We studied a unique set of 300 genomically well-characterized primary PDAC samples with rich clinical annotation. We deconvolved the PDAC transcriptome profiles using CIBERSORTx, leveraging publicly available single-cell RNA-seq data from normal pancreatic tissue and PDAC to estimate cell type proportions in PDAC, and digitally reconstruct cell-specific transcriptional profiles from our study dataset. We built signature matrices and optimized by simulations and comparison to ground truth data. We identified cell-type-specific transcriptional programs that contribute to cancer cell lineage plasticity, especially in the ductal compartment. We also studied cell differentiation hierarchies using CytoTRACE and predict cell lineage trajectories for acinar and ductal cells that we believe are pinpointing relevant information on PDAC progression. Collaborators (Angelo lab, Stanford University) has led the development of the Multiplexed Ion Beam Imaging (MIBI) platform for spatial proteomics. We will use in the very near future MIBI from tissue microarray of 40 PDAC samples to understand the spatial relationship between cancer cell lineage plasticity and stromal cells focused on infiltrating immune cells, using the relevant markers of PDAC plasticity identified from the RNA-seq analysis.

Keywords: deconvolution, imaging, microenvironment, PDAC

Procedia PDF Downloads 99
97 Contribution to the Study of Automatic Epileptiform Pattern Recognition in Long Term EEG Signals

Authors: Christine F. Boos, Fernando M. Azevedo

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Electroencephalogram (EEG) is a record of the electrical activity of the brain that has many applications, such as monitoring alertness, coma and brain death; locating damaged areas of the brain after head injury, stroke and tumor; monitoring anesthesia depth; researching physiology and sleep disorders; researching epilepsy and localizing the seizure focus. Epilepsy is a chronic condition, or a group of diseases of high prevalence, still poorly explained by science and whose diagnosis is still predominantly clinical. The EEG recording is considered an important test for epilepsy investigation and its visual analysis is very often applied for clinical confirmation of epilepsy diagnosis. Moreover, this EEG analysis can also be used to help define the types of epileptic syndrome, determine epileptiform zone, assist in the planning of drug treatment and provide additional information about the feasibility of surgical intervention. In the context of diagnosis confirmation the analysis is made using long term EEG recordings with at least 24 hours long and acquired by a minimum of 24 electrodes in which the neurophysiologists perform a thorough visual evaluation of EEG screens in search of specific electrographic patterns called epileptiform discharges. Considering that the EEG screens usually display 10 seconds of the recording, the neurophysiologist has to evaluate 360 screens per hour of EEG or a minimum of 8,640 screens per long term EEG recording. Analyzing thousands of EEG screens in search patterns that have a maximum duration of 200 ms is a very time consuming, complex and exhaustive task. Because of this, over the years several studies have proposed automated methodologies that could facilitate the neurophysiologists’ task of identifying epileptiform discharges and a large number of methodologies used neural networks for the pattern classification. One of the differences between all of these methodologies is the type of input stimuli presented to the networks, i.e., how the EEG signal is introduced in the network. Five types of input stimuli have been commonly found in literature: raw EEG signal, morphological descriptors (i.e. parameters related to the signal’s morphology), Fast Fourier Transform (FFT) spectrum, Short-Time Fourier Transform (STFT) spectrograms and Wavelet Transform features. This study evaluates the application of these five types of input stimuli and compares the classification results of neural networks that were implemented using each of these inputs. The performance of using raw signal varied between 43 and 84% efficiency. The results of FFT spectrum and STFT spectrograms were quite similar with average efficiency being 73 and 77%, respectively. The efficiency of Wavelet Transform features varied between 57 and 81% while the descriptors presented efficiency values between 62 and 93%. After simulations we could observe that the best results were achieved when either morphological descriptors or Wavelet features were used as input stimuli.

Keywords: Artificial neural network, electroencephalogram signal, pattern recognition, signal processing

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96 Stigma Impacts the Quality of Life of People Living with Diabetes Mellitus in Switzerland: Challenges for Social Work

Authors: Daniel Gredig, Annabelle Bartelsen-Raemy

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Social work services offered to people living with diabetes tend to be moulded by the prevailing understanding that social work is to support people living with diabetes in their adherence to medical prescription and/or life style changes. As diabetes has been conceived as a condition facing no stigma, discrimination of people living with diabetes has not been considered. However, there is growing evidence of stigma. To our knowledge, nevertheless, there have been no comprehensive, in-depth studies of stigma and its impact. Against this background and challenging the present layout of services for people living with diabetes, the present study aimed to establish whether: -people living with diabetes in Switzerland experience stigma, and if so, in what context and to what extent; -experiencing stigma impacts the quality of life of those affected. It was hypothesized that stigma would impact on their quality of life. It was further hypothesized that low self-esteem, psychological distress, depression, and a lack of social support would be mediating factors. For data collection an anonymous paper-and-pencil self-administered questionnaire was used which drew on a qualitative elicitation study. Data were analysed using descriptive statistics and structural equation modelling. To generate a large and diverse convenience sample the questionnaire was distributed to the readers of journal destined to diabetics living in Switzerland issued in German and French. The sample included 3347 people with type 1 and 2 diabetes, aged 16–96, living in diverse living conditions in the German- and French-speaking areas of Switzerland. Respondents reported experiences of discrimination in various contexts and stereotyping based on the belief that diabetics have a low work performance; are inefficient in the workplace; inferior; weak-willed in their ability to manage health-related issues; take advantage of their condition and are viewed as pitiful or sick people. Respondents who reported higher levels of perceived stigma reported higher levels of psychological distress (β = .37), more pronounced depressive symptoms (β=.33), and less social support (β = -.22). Higher psychological distress (β = -.29) and more pronounced depressive symptoms (β = -.28), in turn, predicted lower quality of life. These research findings challenge the prevailing understanding of social work services for people living with diabetes in Switzerland and beyond. They call for a less individualistic approach, the consideration of the social context service users are placed in their everyday life, and addressing stigma. So, social work could partner with people living with diabetes in order to fight against discrimination and stereotypes. This could include identifying and designing educational and public awareness strategies. In direct social work with people living with diabetes, this could include broaching experiences of stigma and modes of coping with. This study was carried out in collaboration with the Swiss Diabetes Association. The association accepted the challenging conclusions from this study. It connected to the results and is currently discussing the priorities and courses of action to be taken.

Keywords: diabetes, discrimination, quality of life, services, stigma

Procedia PDF Downloads 205
95 Fear of Gender-Based Crime and Women Empowerment: An Empirical Study among the Urban Residents of Bangladesh

Authors: Mohammad Ashraful Alam, Biro Judit

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Fear of gender-based crime and fear of crime victimization for women is a major concern in the urban areas of Bangladesh. Based on the recent data from various human rights organizations and international literature the study found that gender-based crime especially sexual assault and rape are increasing in Bangladesh at a significant rate in comparison to other countries. The major focus of the study was to identify the relationship between fear of gender-based crime and women empowerment. To explore the fact the study followed the mixed methodological approach comprising with quantitative and qualitative methods and used secondary information from national and international sources. Corresponding global pictures the present study found that gender, age, complexion, social position, and ethnicity were more common factors of sexual assault and victimization in Bangladesh which lead to women become more fearful about crime victimization than men. Fear of gender-based crime traumatizes women which leads to withdrawal of their non-essential everyday works and some time from the essential works based on their social position, financial status, and social honor in the society. The increasing crime rate also increases the propensity to fear of criminal victimization, traumatization, and feeling of helplessness which make them vulnerable. The patriarchal culture and practices in Bangladesh based on religious culture and established social norms women always feel defenseless therefore they withdraw themselves from various social activities and own interest. Women who have already victimized feel more fear and become traumatized, and who do not victimize yet but know the severity of victimization from the media and others’ have the feeling of fear of crime. Women who find themselves as weak bonding and low networks with their neighbors and living for a short duration have a feeling of more fear and avoid visiting a certain place in a certain time and avoid some social activities. The study found the young women have more possibilities to become victimized through the feeling of fear of crime is higher among elderly women than young. Though women feel fear of all kinds of crime but usually all aged women are more fearful of sexual assault and rape than other violent crimes. Therefore, elderly women and another person in the family does not allow younger girls to go and involve outside activities to secure their family status. On the other hand, fear of crime in public transport is more common to all aged women at a higher level and sometimes they compromise their freedom, independence, financial opportunities, the job only to avoid the perceived threat, and save their social and cultural honor. The study also explores that fear of crime does not always depend on crime rate but the crime news, the severity of the crime, delay justice, the ineffectiveness of police, bail of criminals, corruption and political favoritism, etc. Finally, the study shows that the fear of gender-based crime and violence is working as a potential barrier to ensuring women's empowerment in Bangladesh.

Keywords: compromise personal freedom, fear of crime, fear of gender-based crime, fear of violent crime victimization, rape, sexual assaults, withdrawal from regular activities, women empowerment

Procedia PDF Downloads 113
94 Correlation between the Levels of Some Inflammatory Cytokines/Haematological Parameters and Khorana Scores of Newly Diagnosed Ambulatory Cancer Patients

Authors: Angela O. Ugwu, Sunday Ocheni

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Background: Cancer-associated thrombosis (CAT) is a cause of morbidity and mortality among cancer patients. Several risk factors for developing venous thromboembolism (VTE) also coexist with cancer patients, such as chemotherapy and immobilization, thus contributing to the higher risk of VTE in cancer patients when compared to non-cancer patients. This study aimed to determine if there is any correlation between levels of some inflammatory cytokines/haematological parameters and Khorana scores of newly diagnosed chemotherapy naïve ambulatory cancer patients (CNACP). Methods: This was a cross-sectional analytical study carried out from June 2021 to May 2022. Eligible newly diagnosed cancer patients 18 years and above (case group) were enrolled consecutively from the adult Oncology Clinics of the University of Nigeria Teaching Hospital, Ituku/Ozalla (UNTH). The control group was blood donors at UNTH Ituku/Ozalla, Enugu blood bank, and healthy members of the Medical and Dental Consultants Association of Nigeria (MDCAN), UNTH Chapter. Blood samples collected from the participants were assayed for IL-6, TNF-Alpha, and haematological parameters such as haemoglobin, white blood cell count (WBC), and platelet count. Data were entered into an Excel worksheet and were then analyzed using Statistical Package for Social Sciences (SPSS) computer software version 21.0 for windows. A P value of < 0.05 was considered statistically significant. Results: A total of 200 participants (100 cases and 100 controls) were included in the study. The overall mean age of the participants was 47.42 ±15.1 (range 20-76). The sociodemographic characteristics of the two groups, including age, sex, educational level, body mass index (BMI), and occupation, were similar (P > 0.05). Following One Way ANOVA, there were significant differences between the mean levels of interleukin-6 (IL-6) (p = 0.036) and tumor necrotic factor-α (TNF-α) (p = 0.001) in the three Khorana score groups of the case group. Pearson’s correlation analysis showed a significant positive correlation between the Khorana scores and IL-6 (r=0.28, p = 0.031), TNF-α (r= 0.254, p= 0.011), and PLR (r= 0.240, p=0.016). The mean serum levels of IL-6 were significantly higher in CNACP than in the healthy controls [8.98 (8-12) pg/ml vs. 8.43 (2-10) pg/ml, P=0.0005]. There were also significant differences in the mean levels of the haemoglobin (Hb) level (P < 0.001)); white blood cell (WBC) count ((P < 0.001), and platelet (PL) count (P = 0.005) between the two groups of participants. Conclusion: There is a significant positive correlation between the serum levels of IL-6, TNF-α, and PLR and the Khorana scores of CNACP. The mean serum levels of IL-6, TNF-α, PLR, WBC, and PL count were significantly higher in CNACP than in the healthy controls. Ambulatory cancer patients with high-risk Khorana scores may benefit from anti-inflammatory drugs because of the positive correlation with inflammatory cytokines. Recommendations: Ambulatory cancer patients with 2 Khorana scores may benefit from thromboprophylaxis since they have higher Khorana scores. A multicenter study with a heterogeneous population and larger sample size is recommended in the future to further elucidate the relationship between IL-6, TNF-α, PLR, and the Khorana scores among cancer patients in the Nigerian population.

Keywords: thromboprophylaxis, cancer, Khorana scores, inflammatory cytokines, haematological parameters

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93 An Evaluation of a First Year Introductory Statistics Course at a University in Jamaica

Authors: Ayesha M. Facey

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The evaluation sought to determine the factors associated with the high failure rate among students taking a first-year introductory statistics course. By utilizing Tyler’s Objective Based Model, the main objectives were: to assess the effectiveness of the lecturer’s teaching strategies; to determine the proportion of students who attends lectures and tutorials frequently and to determine the impact of infrequent attendance on performance; to determine how the assigned activities assisted in students understanding of the course content; to ascertain the possible issues being faced by students in understanding the course material and obtain possible solutions to the challenges and to determine whether the learning outcomes have been achieved based on an assessment of the second in-course examination. A quantitative survey research strategy was employed and the study population was students enrolled in semester one of the academic year 2015/2016. A convenience sampling approach was employed resulting in a sample of 98 students. Primary data was collected using self-administered questionnaires over a one-week period. Secondary data was obtained from the results of the second in-course examination. Data were entered and analyzed in SPSS version 22 and both univariate and bivariate analyses were conducted on the information obtained from the questionnaires. Univariate analyses provided description of the sample through means, standard deviations and percentages while bivariate analyses were done using Spearman’s Rho correlation coefficient and Chi-square analyses. For secondary data, an item analysis was performed to obtain the reliability of the examination questions, difficulty index and discriminant index. The examination results also provided information on the weak areas of the students and highlighted the learning outcomes that were not achieved. Findings revealed that students were more likely to participate in lectures than tutorials and that attendance was high for both lectures and tutorials. There was a significant relationship between participation in lectures and performance on examination. However, a high proportion of students has been absent from three or more tutorials as well as lectures. A higher proportion of students indicated that they completed the assignments obtained from the lectures sometimes while they rarely completed tutorial worksheets. Students who were more likely to complete their assignments were significantly more likely to perform well on their examination. Additionally, students faced a number of challenges in understanding the course content and the topics of probability, binomial distribution and normal distribution were the most challenging. The item analysis also highlighted these topics as problem areas. Problems doing mathematics and application and analyses were their major challenges faced by students and most students indicated that some of the challenges could be alleviated if additional examples were worked in lectures and they were given more time to solve questions. Analysis of the examination results showed that a number of learning outcomes were not achieved for a number of topics. Based on the findings recommendations were made that suggested adjustments to grade allocations, delivery of lectures and methods of assessment.

Keywords: evaluation, item analysis, Tyler’s objective based model, university statistics

Procedia PDF Downloads 173
92 An in silico Approach for Exploring the Intercellular Communication in Cancer Cells

Authors: M. Cardenas-Garcia, P. P. Gonzalez-Perez

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Intercellular communication is a necessary condition for cellular functions and it allows a group of cells to survive as a population. Throughout this interaction, the cells work in a coordinated and collaborative way which facilitates their survival. In the case of cancerous cells, these take advantage of intercellular communication to preserve their malignancy, since through these physical unions they can send signs of malignancy. The Wnt/β-catenin signaling pathway plays an important role in the formation of intercellular communications, being also involved in a large number of cellular processes such as proliferation, differentiation, adhesion, cell survival, and cell death. The modeling and simulation of cellular signaling systems have found valuable support in a wide range of modeling approaches, which cover a wide spectrum ranging from mathematical models; e.g., ordinary differential equations, statistical methods, and numerical methods– to computational models; e.g., process algebra for modeling behavior and variation in molecular systems. Based on these models, different simulation tools have been developed from mathematical ones to computational ones. Regarding cellular and molecular processes in cancer, its study has also found a valuable support in different simulation tools that, covering a spectrum as mentioned above, have allowed the in silico experimentation of this phenomenon at the cellular and molecular level. In this work, we simulate and explore the complex interaction patterns of intercellular communication in cancer cells using the Cellulat bioinformatics tool, a computational simulation tool developed by us and motivated by two key elements: 1) a biochemically inspired model of self-organizing coordination in tuple spaces, and 2) the Gillespie’s algorithm, a stochastic simulation algorithm typically used to mimic systems of chemical/biochemical reactions in an efficient and accurate way. The main idea behind the Cellulat simulation tool is to provide an in silico experimentation environment that complements and guides in vitro experimentation in intra and intercellular signaling networks. Unlike most of the cell signaling simulation tools, such as E-Cell, BetaWB and Cell Illustrator which provides abstractions to model only intracellular behavior, Cellulat is appropriate for modeling both intracellular signaling and intercellular communication, providing the abstractions required to model –and as a result, simulate– the interaction mechanisms that involve two or more cells, that is essential in the scenario discussed in this work. During the development of this work we made evident the application of our computational simulation tool (Cellulat) for the modeling and simulation of intercellular communication between normal and cancerous cells, and in this way, propose key molecules that may prevent the arrival of malignant signals to the cells that surround the tumor cells. In this manner, we could identify the significant role that has the Wnt/β-catenin signaling pathway in cellular communication, and therefore, in the dissemination of cancer cells. We verified, using in silico experiments, how the inhibition of this signaling pathway prevents that the cells that surround a cancerous cell are transformed.

Keywords: cancer cells, in silico approach, intercellular communication, key molecules, modeling and simulation

Procedia PDF Downloads 232
91 Effect of Degree of Phosphorylation on Electrospinning and In vitro Cell Behavior of Phosphorylated Polymers as Biomimetic Materials for Tissue Engineering Applications

Authors: Pallab Datta, Jyotirmoy Chatterjee, Santanu Dhara

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Over the past few years, phosphorous containing polymers have received widespread attention for applications such as high performance optical fibers, flame retardant materials, drug delivery and tissue engineering. Being pentavalent, phosphorous can exist in different chemical environments in these polymers which increase their versatility. In human biochemistry, phosphorous based compounds exert their functions both in soluble and insoluble form occurring as inorganic or as organophosphorous compounds. Specifically in case of biomacromolecules, phosphates are critical for functions of DNA, ATP, phosphoproteins, phospholipids, phosphoglycans and several coenzymes. Inspired by the role of phosphorous in functional biomacromolecules, design and synthesis of biomimetic materials are thus carried out by several authors to study macromolecular function or as substitutes in clinical tissue regeneration conditions. In addition, many regulatory signals of the body are controlled by phoshphorylation of key proteins present either in form of growth factors or matrix-bound scaffold proteins. This inspires works on synthesis of phospho-peptidomimetic amino acids for understanding key signaling pathways and this is extended to obtain molecules with potentially useful biological properties. Apart from above applications, phosphate groups bound to polymer backbones have also been demonstrated to improve function of osteoblast cells and augment performance of bone grafts. Despite the advantages of phosphate grafting, however, there is limited understanding on effect of degree of phosphorylation on macromolecular physicochemical and/or biological properties. Such investigations are necessary to effectively translate knowledge of macromolecular biochemistry into relevant clinical products since they directly influence processability of these polymers into suitable scaffold structures and control subsequent biological response. Amongst various techniques for fabrication of biomimetic scaffolds, nanofibrous scaffolds fabricated by electrospinning technique offer some special advantages in resembling the attributes of natural extracellular matrix. Understanding changes in physico-chemical properties of polymers as function of phosphorylation is therefore going to be crucial in development of nanofiber scaffolds based on phosphorylated polymers. The aim of the present work is to investigate the effect of phosphorous grafting on the electrospinning behavior of polymers with aim to obtain biomaterials for bone regeneration applications. For this purpose, phosphorylated derivatives of two polymers of widely different electrospinning behaviors were selected as starting materials. Poly(vinyl alcohol) is a conveniently electrospinnable polymer at different conditions and concentrations. On the other hand, electrospinning of chitosan backbone based polymers have been viewed as a critical challenge. The phosphorylated derivatives of these polymers were synthesized, characterized and electrospinning behavior of various solutions containing these derivatives was compared with electrospinning of pure poly (vinyl alcohol). In PVA, phosphorylation adversely impacted electrospinnability while in NMPC, higher phosphate content widened concentration range for nanofiber formation. Culture of MG-63 cells on electrospun nanofibers, revealed that degree of phosphate modification of a polymer significantly improves cell adhesion or osteoblast function of cultured cells. It is concluded that improvement of cell response parameters of nanofiber scaffolds can be attained as a function of controlled degree of phosphate grafting in polymeric biomaterials with implications for bone tissue engineering applications.

Keywords: bone regeneration, chitosan, electrospinning, phosphorylation

Procedia PDF Downloads 199
90 Dynamic Changes in NT-proBNP Levels in Unrelated Donors during Hematopoietic Stem Cells Mobilization

Authors: Natalia V. Minaeva, Natalia A. Zorina, Marina N. Khorobrikh, Philipp S. Sherstnev, Tatiana V. Krivokorytova, Alexander S. Luchinin, Maksim S. Minaev, Igor V. Paramonov

Abstract:

Background. Over the last few decades, the Center for International Blood and Marrow Transplant Research (CIBMTR) and the World Marrow Donor Association (WMDA) have been actively working to ensure the safety of the hematopoietic stem cell (HSC) donation process. Registration of adverse events that may occur during the donation period and establishing a relationship between donation and side effects are included in the WMDA international standards. The level of blood serum N-terminal pro-brain natriuretic peptide (NT-proBNP) is an early marker of myocardial stress. Due to the high analytical sensitivity and specificity, laboratory assessment of NT-proBNP makes it possible to objectively diagnose myocardial dysfunction. It is well known that the main stimulus for proBNP synthesis and secretion from atrial and ventricular cardiac myocytes is myocyte stretch and increasement of myocardial extensibility and pressure in the heart chambers. Аim. The aim of the study was to assess the dynamic changes in the levels of blood serum N-terminal pro-brain natriuretic peptide of unrelated donors at various stages of hematopoietic stem cell mobilization. Materials. We have examined 133 unrelated donors, including 92 men and 41 women, that have been included into the study. The NT-proBNP levels were measured before the start of mobilization, then on the day of apheresis, and after the donation of allogeneic HSC. The relationship between NT-proBNP levels and body mass index (BMI), ferritin, hemoglobin, and white blood cells (WBC) levels was assessed on the day of apheresis. The median age of donors was 34 years. Mobilization of HSCs was managed with filgrastim administration at a dose of 10 μg/kg daily for 4-5 days. The first leukocytapheresis was performed on day 4 from the start of filgrastim administration. Quantitative values of the blood serum NT-proBNP level are presented as a median (Me), first and third quartiles (Q1-Q3). Comparative analysis was carried out using the t-test and correlation analysis as well by Spearman method. Results. The baseline blood serum NT-proBNP levels in all 133 donors were within the reference values (<125 pg/ml) and equaled 21,6 (10,0; 43,3) pg/ml. At the same time, the level of NT-proBNP in women was significantly higher than that of men. On the day of the HSC apheresis, a significant increase of blood serum NT-proBNP levels was detected and equald 131,2 (72,6; 165,3) pg/ml (p<0,001), with higher rates in female donors. A statistically significant weak inverse correleation was established between the level of NT-proBNP and the BMI of donors (-0.18, p = 0,03), as well as the level of hemoglobin (-0.33, p <0,001), and ferritin levels (-0.19, p = 0,03). No relationship has been established between the magnitude of WBC levels achieved as a result of the mobilization of HSC on the day of leukocytapheresis. A day after the apheresis, the blood serum NT-proBNP levels still exceeded the reference values, but there was a decreasing tendency. Conclusion. An increase of the blood serum NT-proBNP level in unrelated donors during the mobilization of HSC was established. Future studies should clarify the reason for this phenomenon, as well as its effects on donors' long-term health.

Keywords: unrelated donors, mobilization, hematopoietic stem cells, N-terminal pro-brain natriuretic peptide

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89 Molecular Characterization, Host Plant Resistance and Epidemiology of Bean Common Mosaic Virus Infecting Cowpea (Vigna unguiculata L. Walp)

Authors: N. Manjunatha, K. T. Rangswamy, N. Nagaraju, H. A. Prameela, P. Rudraswamy, M. Krishnareddy

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The identification of virus in cowpea especially potyviruses is confusing. Even though there are several studies on viruses causing diseases in cowpea, difficult to distinguish based on symptoms and serological detection. The differentiation of potyviruses considering as a constraint, the present study is initiated for molecular characterization, host plant resistance and epidemiology of the BCMV infecting cowpea. The etiological agent causing cowpea mosaic was identified as Bean Common Mosaic Virus (BCMV) on the basis of RT-PCR and electron microscopy. An approximately 750bp PCR product corresponding to coat protein (CP) region of the virus and the presence of long flexuous filamentous particles measuring about 952 nm in size typical to genus potyvirus were observed under electron microscope. The characterized virus isolate genome had 10054 nucleotides, excluding the 3’ terminal poly (A) tail. Comparison of polyprotein of the virus with other potyviruses showed similar genome organization with 9 cleavage sites resulted in 10 functional proteins. The pairwise sequence comparison of individual genes, P1 showed most divergent, but CP gene was less divergent at nucleotide and amino acid level. A phylogenetic tree constructed based on multiple sequence alignments of the polyprotein nucleotide and amino acid sequences of cowpea BCMV and potyviruses showed virus is closely related to BCMV-HB. Whereas, Soybean variant of china (KJ807806) and NL1 isolate (AY112735) showed 93.8 % (5’UTR) and 94.9 % (3’UTR) homology respectively with other BCMV isolates. This virus transmitted to different leguminous plant species and produced systemic symptoms under greenhouse conditions. Out of 100 cowpea genotypes screened, three genotypes viz., IC 8966, V 5 and IC 202806 showed immune reaction in both field and greenhouse conditions. Single marker analysis (SMA) was revealed out of 4 SSR markers linked to BCMV resistance, M135 marker explains 28.2 % of phenotypic variation (R2) and Polymorphic information content (PIC) value of these markers was ranged from 0.23 to 0.37. The correlation and regression analysis showed rainfall, and minimum temperature had significant negative impact and strong relationship with aphid population, whereas weak correlation was observed with disease incidence. Path coefficient analysis revealed most of the weather parameters exerted their indirect contributions to the aphid population and disease incidence except minimum temperature. This study helps to identify specific gaps in knowledge for researchers who may wish to further analyse the science behind complex interactions between vector-virus and host in relation to the environment. The resistant genotypes identified are could be effectively used in resistance breeding programme.

Keywords: cowpea, epidemiology, genotypes, virus

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88 Intriguing Modulations in the Excited State Intramolecular Proton Transfer Process of Chrysazine Governed by Host-Guest Interactions with Macrocyclic Molecules

Authors: Poojan Gharat, Haridas Pal, Sharmistha Dutta Choudhury

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Tuning photophysical properties of guest dyes through host-guest interactions involving macrocyclic hosts are the attractive research areas since past few decades, as these changes can directly be implemented in chemical sensing, molecular recognition, fluorescence imaging and dye laser applications. Excited state intramolecular proton transfer (ESIPT) is an intramolecular prototautomerization process display by some specific dyes. The process is quite amenable to tunability by the presence of different macrocyclic hosts. The present study explores the interesting effect of p-sulfonatocalix[n]arene (SCXn) and cyclodextrin (CD) hosts on the excited-state prototautomeric equilibrium of Chrysazine (CZ), a model antitumour drug. CZ exists exclusively in its normal form (N) in the ground state. However, in the excited state, the excited N* form undergoes ESIPT along with its pre-existing intramolecular hydrogen bonds, giving the excited state prototautomer (T*). Accordingly, CZ shows a single absorption band due to N form, but two emission bands due to N* and T* forms. Facile prototautomerization of CZ is considerably inhibited when the dye gets bound to SCXn hosts. However, in spite of lower binding affinity, the inhibition is more profound with SCX6 host as compared to SCX4 host. For CD-CZ system, while prototautomerization process is hindered by the presence of β-CD, it remains unaffected in the presence of γCD. Reduction in the prototautomerization process of CZ by SCXn and βCD hosts is unusual, because T* form is less dipolar in nature than the N*, hence binding of CZ within relatively hydrophobic hosts cavities should have enhanced the prototautomerization process. At the same time, considering the similar chemical nature of two CD hosts, their effect on prototautomerization process of CZ would have also been similar. The atypical effects on the prototautomerization process of CZ by the studied hosts are suggested to arise due to the partial inclusion or external binding of CZ with the hosts. As a result, there is a strong possibility of intermolecular H-bonding interaction between CZ dye and the functional groups present at the portals of SCXn and βCD hosts. Formation of these intermolecular H-bonds effectively causes the pre-existing intramolecular H-bonding network within CZ molecule to become weak, and this consequently reduces the prototautomerization process for the dye. Our results suggest that rather than the binding affinity between the dye and host, it is the orientation of CZ in the case of SCXn-CZ complexes and the binding stoichiometry in the case of CD-CZ complexes that play the predominant role in influencing the prototautomeric equilibrium of the dye CZ. In the case of SCXn-CZ complexes, the results obtained through experimental findings are well supported by quantum chemical calculations. Similarly for CD-CZ systems, binding stoichiometries obtained through geometry optimization studies on the complexes between CZ and CD hosts correlate nicely with the experimental results. Formation of βCD-CZ complexes with 1:1 stoichiometry while formation of γCD-CZ complexes with 1:1, 1:2 and 2:2 stoichiometries are revealed from geometry optimization studies and these results are in good accordance with the observed effects by the βCD and γCD hosts on the ESIPT process of CZ dye.

Keywords: intermolecular proton transfer, macrocyclic hosts, quantum chemical studies, photophysical studies

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87 Effects of Tramadol Administration on the Ovary of Adult Rats and the Possible Recovery after Tramadol Withdrawal: A Light and Electron Microscopic Study

Authors: Heba Kamal Mohamed

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Introduction: Tramadol is a weak -opioid receptor agonist with an analgesic effect because of the inhibition of uptake of norepinephrine and serotonin. Nowadays, tramadol hydrochloride is frequently used as a pain reliever. Tramadol is recommended for the management of acute and chronic pain of moderate to severe intensity associated with a variety of diseases or problems, including osteoarthritis, diabetic neuropathy, neuropathic pain, and even perioperative pain in human patients. In obstetrics and gynecology, tramadol is used extensively to treat postoperative pain. Aim of the study: This study was undertaken to investigate the histological (light and electron microscopic) and immunohistochemical effects of long term tramadol treatment on the ovary of adult rats and the possible recovery after tramadol withdrawal. Design: Experimental study. Materials and methods: Thirty adult female albino rats were used in this study. They were classified into three main groups (10 rats each). Group I served as the control group. Group II, rats were subcutaneously injected with tramadol 40 mg/kg three times per week for 8 weeks. Group III, rats were subcutaneously injected with tramadol 40 mg/kg three times per week for 8 weeks then were kept for another 8 weeks without treatment for recovery. At the end of the experiment rats were sacrificed and bilateral oophorectomy was carried out; the ovaries were processed for histological study (light and electron microscopic) and immunohistochemical reaction for caspase-3 (apoptotic protein). Results: Examination of the ovary of tramadol-treated rats (group II) revealed many atretic ovarian follicles, some follicles showed detachment of the oocyte from surrounding granulosa cells and others showed loss of the oocyte. Many follicles revealed degenerated vacuolated oocytes and vacuolated theca folliculi cells. Granulosa cells appeared shrunken, disrupted and loosely attached with vacuolated cytoplasm and pyknotic nuclei. Some follicles showed separation of granulosa cells from the theca folliculi layer. The ultrastructural study revealed the presence of granulosa cells with electron dense indented nuclei, damaged mitochondria and granular vacuolated cytoplasm. Other cells showed accumulation of large amount of lipid droplets in their cytoplasm. Some follicles revealed rarifaction of the cytoplasm of oocytes and absent zona pellucida. Moreover, apoptotic changes were detected by immunohistochemical staining in the form of increased staining intensity to caspase-3 (apoptotic protein). With Masson's Trichrome stain, there was an increased collagen fibre deposition in the ovarian cortical stroma. The wall of blood vessels appeared thickened. In the withdrawal group (group III), there was a little improvement in the histological and immunohistochemical changes. Conclusion: Tramadol had serious deleterious effects on ovarian structure. Thus, it should be used with caution, especially when a long term treatment is indicated. Withdrawal of tramadol led to a little improvement in the structural impairment of the ovary.

Keywords: tramadol, ovary, withdrawal, rats

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86 An Investigation into Why Very Few Small Start-Ups Business Survive for Longer Than Three Years: An Explanatory Study in the Context of Saudi Arabia

Authors: Motaz Alsolaim

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Nowadays, the challenges of running a start-up can be very complex and are perhaps more difficult than at any other time in the past. Changes in technology, manufacturing innovation, and product development, combined with intense competition and market regulations are factors that have put pressure on classic ways of managing firms, thereby forcing change. As a result, the rate of closure, exit or discontinuation of start-ups and young businesses is very high. Despite the essential role of small firms in an economy, they still tend to face obstacles that exert a negative influence on their performance and rate of survival. In fact, it is not easy to determine with any certainty the reasons why small firms fail. For this reason, failure itself is not clearly defined, and its exact causes are hard to diagnose. In this current study, therefore, the barriers to survival will be covered more broadly, especially personal/entrepreneurial, enterprise and environmental factors with regard to various possible reasons for this failure, in order to determine the best solutions and make appropriate recommendations. Methodology: It could be argued that mixed methods might help to improve entrepreneurship research addressing challenges emphasis in previous studies and to achieve the triangulation. Calls for the combined use of quantitative and qualitative research were also made in the entrepreneurship field since entrepreneurship is a multi-faceted area of research. Therefore, explanatory sequential mixed method was used, using questionnaire online survey for entrepreneurs, followed by semi-structure interview. Collecting over 750 surveys and accepting 296 valid surveys, after that 13 interviews from government official seniors, businessmen successful entrepreneurs, and non-successful entrepreneurs. Findings: The first phase findings ( quantitative) shows the obstacles to survive; starting from the personal/ entrepreneurial factors such as; past work experience, lack of skills and interest, are positive factors, while; gender, age and education level of the owner are negative factors. Internal factors such as lack of marketing research and weak business planning are positive. The environmental factors; in economic perspectives; difficulty to find labors, in socio-cultural perspectives; Social restriction and traditions found to be a negative factors. In other hand, from the political perspective; cost of compliance and insufficient government plans found to be a positive factors for small business failure. From infrastructure perspective; lack of skills labor, high level of bureaucracy and lack of information are positive factors. Conclusion: This paper serves to enrich the understanding of failure factors in MENA region more precisely in SA, by minimizing the probability of failure in small-micro entrepreneurial start-up in SA, in the light of the Saudi government’s Vision 2030 plan.

Keywords: small business barriers, start-up business, entrepreneurship, Saudi Arabia

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85 Crafting Robust Business Model Innovation Path with Generative Artificial Intelligence in Start-up SMEs

Authors: Ignitia Motjolopane

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Small and medium enterprises (SMEs) play an important role in economies by contributing to economic growth and employment. In the fourth industrial revolution, the convergence of technologies and the changing nature of work created pressures on economies globally. Generative artificial intelligence (AI) may support SMEs in exploring, exploiting, and transforming business models to align with their growth aspirations. SMEs' growth aspirations fall into four categories: subsistence, income, growth, and speculative. Subsistence-oriented firms focus on meeting basic financial obligations and show less motivation for business model innovation. SMEs focused on income, growth, and speculation are more likely to pursue business model innovation to support growth strategies. SMEs' strategic goals link to distinct business model innovation paths depending on whether SMEs are starting a new business, pursuing growth, or seeking profitability. Integrating generative artificial intelligence in start-up SME business model innovation enhances value creation, user-oriented innovation, and SMEs' ability to adapt to dynamic changes in the business environment. The existing literature may lack comprehensive frameworks and guidelines for effectively integrating generative AI in start-up reiterative business model innovation paths. This paper examines start-up business model innovation path with generative artificial intelligence. A theoretical approach is used to examine start-up-focused SME reiterative business model innovation path with generative AI. Articulating how generative AI may be used to support SMEs to systematically and cyclically build the business model covering most or all business model components and analyse and test the BM's viability throughout the process. As such, the paper explores generative AI usage in market exploration. Moreover, market exploration poses unique challenges for start-ups compared to established companies due to a lack of extensive customer data, sales history, and market knowledge. Furthermore, the paper examines the use of generative AI in developing and testing viable value propositions and business models. In addition, the paper looks into identifying and selecting partners with generative AI support. Selecting the right partners is crucial for start-ups and may significantly impact success. The paper will examine generative AI usage in choosing the right information technology, funding process, revenue model determination, and stress testing business models. Stress testing business models validate strong and weak points by applying scenarios and evaluating the robustness of individual business model components and the interrelation between components. Thus, the stress testing business model may address these uncertainties, as misalignment between an organisation and its environment has been recognised as the leading cause of company failure. Generative AI may be used to generate business model stress-testing scenarios. The paper is expected to make a theoretical and practical contribution to theory and approaches in crafting a robust business model innovation path with generative artificial intelligence in start-up SMEs.

Keywords: business models, innovation, generative AI, small medium enterprises

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84 Innovative Strategies for Chest Wall Reconstruction Following Resection of Recurrent Breast Carcinoma

Authors: Sean Yao Zu Kong, Khong Yik Chew

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Introduction: We described a case report of the successful use of advanced surgical techniques in a patient with recurrent breast cancer who underwent a wide resection including the hemi-sternum, clavicle, multiple ribs, and a lobe of the lung due to tumor involvement. This extensive resection exposed critical structures, requiring a creative approach to reconstruction. To address this complex chest wall reconstruction, a free fibula flap and a 4-zone rectus abdominis musculocutaneous flap were successfully utilized. The use of a free vascularized bone flap allowed for rapid osteointegration and resistance against osteoradionecrosis after adjuvant radiation, while a four-zone tram flap allowed for reconstruction of both the chest wall and breast mound. Although limited recipient vessels made free flaps challenging, the free fibula flap served as both a bony reconstruction and vascular conduit, supercharged with the distal peroneal artery and veins of the peroneal artery from the fibula graft. Our approach highlights the potential of advanced surgical techniques to improve outcomes in complex cases of chest wall reconstruction in patients with recurrent breast cancer, which is becoming increasingly relevant as breast cancer incidence rates increases. Case presentation: This report describes a successful reconstruction of a patient with recurrent breast cancer who required extensive resection, including the anterior chest wall, clavicle, and sternoclavicular joint. Challenges arose due to the loss of accessory muscles and the non-rigid rib cage, which could lead to compromised ventilation and instability. A free fibula osteocutaneous flap and a four-zone TRAM flap with vascular supercharging were utilized to achieve long-term stability and function. The patient has since fully recovered, and during the review, both flaps remained viable, and chest mound reconstruction was satisfactory. A planned nipple/areolar reconstruction was offered pending the patient’s decision after adjuvant radiotherapy. Conclusion: In conclusion, this case report highlights the successful use of innovative surgical techniques in addressing a complex case of recurrent breast cancer requiring extensive resection and radical reconstruction. Our approach, utilized a combination of a free fibula flap and a 4-zone rectus abdominis musculocutaneous flap, demonstrates the potential for advanced techniques in chest wall reconstruction to minimize complications and ensure long-term stability and function. As the incidence of breast cancer continues to rise, it is crucial that healthcare professionals explore and utilize innovative techniques to improve patient outcomes and quality of life.

Keywords: free fibula flap, rectus abdominis musculocutaneous flap, post-adjuvant radiotherapy, reconstructive surgery, malignancy

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83 Working Memory and Audio-Motor Synchronization in Children with Different Degrees of Central Nervous System's Lesions

Authors: Anastasia V. Kovaleva, Alena A. Ryabova, Vladimir N. Kasatkin

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Background: The most simple form of entrainment to a sensory (typically auditory) rhythmic stimulus involves perceiving and synchronizing movements with an isochronous beat with one level of periodicity, such as that produced by a metronome. Children with pediatric cancer usually treated with chemo- and radiotherapy. Because of such treatment, psychologists and health professionals declare cognitive and motor abilities decline in cancer patients. The purpose of our study was to measure working memory characteristics with association with audio-motor synchronization tasks, also involved some memory resources, in children with different degrees of central nervous system lesions: posterior fossa tumors, acute lymphoblastic leukemia, and healthy controls. Methods: Our sample consisted of three groups of children: children treated for posterior fossa tumors (PFT-group, n=42, mean age 12.23), children treated for acute lymphoblastic leukemia (ALL-group, n=11, mean age 11.57) and neurologically healthy children (control group, n=36, mean age 11.67). Participants were tested for working memory characteristics with Cambridge Neuropsychological Test Automated Battery (CANTAB). Pattern recognition memory (PRM) and spatial working memory (SWM) tests were applied. Outcome measures of PRM test include the number and percentage of correct trials and latency (speed of participant’s response), and measures of SWM include errors, strategy, and latency. In the synchronization tests, the instruction was to tap out a regular beat (40, 60, 90 and 120 beats per minute) in synchrony with the rhythmic sequences that were played. This meant that for the sequences with an isochronous beat, participants were required to tap into every auditory event. Variations of inter-tap-intervals and deviations of children’s taps from the metronome were assessed. Results: Analysis of variance revealed the significant effect of group (ALL, PFT and control) on such parameters as short-term PRM, SWM strategy and errors. Healthy controls demonstrated more correctly retained elements, better working memory strategy, compared to cancer patients. Interestingly that ALL patients chose the bad strategy, but committed significantly less errors in SWM test then PFT and controls did. As to rhythmic ability, significant associations of working memory were found out only with 40 bpm rhythm: the less variable were inter-tap-intervals of the child, the more elements in memory he/she could retain. The ability to audio-motor synchronization may be related to working memory processes mediated by the prefrontal cortex whereby each sensory event is actively retrieved and monitored during rhythmic sequencing. Conclusion: Our results suggest that working memory, tested with appropriate cognitive methods, is associated with the ability to synchronize movements with rhythmic sounds, especially in sub-second intervals (40 per minute).

Keywords: acute lymphoblastic leukemia (ALL), audio-motor synchronization, posterior fossa tumor, working memory

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