Search results for: overall survival
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1111

Search results for: overall survival

781 Triple Immunotherapy to Overcome Immune Evasion by Tumors in a Melanoma Mouse Model

Authors: Mary-Ann N. Jallad, Dalal F. Jaber, Alexander M. Abdelnoor

Abstract:

Introduction: Current evidence confirms that both innate and adaptive immune systems are capable of recognizing and abolishing malignant cells. The emergence of cancerous tumors in patients is, therefore, an indication that certain cancer cells can resist elimination by the immune system through a process known as “immune evasion”. In fact, cancer cells often exploit regulatory mechanisms to escape immunity. Such mechanisms normally exist to control the immune responses and prohibit exaggerated or autoimmune reactions. Recently, immunotherapies have shown promising yet limited results. Therefore this study investigates several immunotherapeutic combinations and devises a triple immunotherapy which harnesses the innate and acquired immune responses towards the annihilation of malignant cells through overcoming their ability of immune evasion, consequently hampering malignant progression and eliminating established tumors. The aims of the study are to rule out acute/chronic toxic effects of the proposed treatment combinations, to assess the effect of these combinations on tumor growth and survival rates, and to investigate potential mechanisms underlying the phenotypic results through analyzing serum levels of anti-tumor cytokines, angiogenic factors and tumor progression indicator, and the tumor-infiltrating immune-cells populations. Methodology: For toxicity analysis, cancer-free C57BL/6 mice are randomized into 9 groups: Group 1 untreated, group 2 treated with sterile saline (solvent of used treatments), group 3 treated with Monophosphoryl-lipid-A, group 4 with anti-CTLA4-antibodies, group 5 with 1-Methyl-Tryptophan (Indolamine-Dioxygenase-1 inhibitor), group 6 with both MPLA and anti-CTLA4-antibodies, group 7 with both MPLA and 1-MT, group 8 with both anti-CTLA4-antibodies and 1-MT, and group 9 with all three: MPLA, anti-CTLA4-antibodies and 1-MT. Mice are monitored throughout the treatment period and for three following months. At that point, histological sections from their main organs are assessed. For tumor progression and survival analysis, a murine melanoma model is generated by injecting analogous mice with B16F10 melanoma cells. These mice are segregated into the listed nine groups. Their tumor size and survival are monitored. For a depiction of underlying mechanisms, melanoma-bearing mice from each group are sacrificed at several time-points. Sera are tested to assess the levels of Interleukin-12 (IL-12), Vascular-Endothelial-Growth Factor (VEGF), and S100B. Furthermore, tumors are excised for analysis of infiltrated immune cell populations including T-cells, macrophages, natural killer cells and immune-regulatory cells. Results: Toxicity analysis shows that all treated groups present no signs of neither acute nor chronic toxicity. Their appearance and weights were comparable to those of control groups throughout the treatment period and for the following 3 months. Moreover, histological sections from their hearts, kidneys, lungs, and livers were normal. Work is ongoing for completion of the remaining study aims. Conclusion: Toxicity was the major concern for the success of the proposed comprehensive combinational therapy. Data generated so far ruled out any acute or chronic toxic effects. Consequently, ongoing work is quite promising and may significantly contribute to the development of more effective immunotherapeutic strategies for the treatment of cancer patients.

Keywords: cancer immunotherapy, check-point blockade, combination therapy, melanoma

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780 The Contemporary Issues of Quality Management: Relationship between Total Quality Management and Knowledge Management

Authors: Mehrnoosh Askarizadeh

Abstract:

To meet the challenges of the new global environment, companies have started paying great attention towards quality management as an integral part of their strategic business plans. The purpose of this article is to investigate the relationship between total quality management (TQM) and knowledge management (KM). Successful total quality management implementation throughout the organizations requires major changes in the main four aspects of knowledge management, namely: Creating, storage, sharing and application. Skill, knowledge and productivity are important factors in organization’s success and have important role. Therefore, TQM management system pays special attention to it. However, knowledge as the source is essential for organization’s survival. Our study points out how the quality management and knowledge management have been incorporated into each other for the development of the quality culture within the organization.

Keywords: knowledge management (KM), total quality management (TQM), organizational performance (OP), deming cycle

Procedia PDF Downloads 481
779 Data Science Inquiry to Manage Football Referees’ Careers

Authors: Iñaki Aliende, Tom Webb, Lorenzo Escot

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There is a concern about the decrease in football referees globally. A study in Spain has analyzed the factors affecting a referee's career over the past 30 years through a survey of 758 referees. Results showed the impact of factors such as threats, education, initial vocation, and dependents on a referee's career. To improve the situation, the federation needs to provide better information, support young referees, monitor referees, and raise public awareness of violence toward referees. The study also formed a comprehensive model for federations to enhance their officiating policies by means of data-driven techniques that can serve other federations to improve referees' careers.

Keywords: data science, football referees, sport management, sport careers, survival analysis

Procedia PDF Downloads 99
778 Metformin Protects Cardiac Muscle against the Pro-Apoptotic Effects of Hyperglycaemia, Elevated Fatty Acid and Nicotine

Authors: Christopher R. Triggle, Hong Ding, Khaled Machaca, Gnanapragasam Arunachalam

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The antidiabetic drug, metformin, has been in clinical use for over 50 years and remains the first choice drug for the treatment of type two diabetes. In addition to its effectiveness as an oral anti-hyperglycaemic drug metformin also possesses vasculoprotective effects that are assumed to be secondary to its ability to reduce insulin resistance and control glycated hemoglobin levels; however, recent data from our laboratory indicate that metformin also has direct vasoprotective effects that are mediated, at least in part, via the anti-ageing gene, SIRT1. Diabetes is a major risk factor for the development of cardiovascular disease (CVD) and it is also well established that tobacco use further enhances the risk of CVD; however, it is not known whether treatment with metformin can offset the negative effects of diabetes and tobacco use on cardiac function. The current study was therefore designed to investigate 1: the effects of hyperglycaemia (HG) either alone or in the presence of elevated fatty acids (palmitate) and nicotine on the protein expression levels of the deacetylase sirtuin 1 (the protein product of SIRT1), anti-apoptotic Bcl-2, pro-apoptotic BIM and the pro-apoptotic, tumour suppressor protein, acetylated p53 in cardiomyocytes. 2: the ability of metformin to prevent the detrimental effects of HG, palmitate and nicotine on cardiomyocyte survival. Cell culture protocols were designed using a rat cardiomyocyte cell line, H9c2, either under normal glycaemic (NG) conditions of 5.5mM glucose, or hyperglycaemic conditions (HG) of 25mM glucose with, or without, added palmitate (250μM) or nicotine (1.0mM) for 24h. Immuno-blotting was used to detect the expression of sirtuin 1, Bcl-2, BIM, acetylated (Ac)-p53, p53 with β-actin used as the reference protein. Exposure to HG, palmitate, or nicotine alone significantly reduced expression of sirtuin1, Bcl-2 and raised the expression levels of acetylated p53 and BIM; however, the combination of HG, palmitate and nicotine had a synergistic effect to significantly suppress the expression levels of sirtuin 1 and Bcl-2, but further enhanced the expression of Ac-p53, and BIM. The inclusion of 1000μM, but not 50μM, metformin in the H9c2 cell culture protocol prevented the effects of HG, palmitate and nicotine on the pro-apoptotic pathways. Collectively these data indicate that metformin, in addition to its anti-hyperglycaemic and vasculoprotective properties, also has direct cardioprotective actions that offset the negative effects of hyerglycaemia, elevated free fatty acids and nicotine on cardiac cell survival. These data are of particular significance for the treatment of patients with diabetes who are also smokers as the inclusion of metformin in their therapeutic treatment plan should help reduce cardiac-related morbidity and mortality.

Keywords: apoptosis, cardiac muscle, diabetes, metformin, nicotine

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777 Zoledronic Acid with Neoadjuvant Chemotherapy in Advanced Breast Cancer Prospective Study 2011–2014

Authors: S. Sakhri

Abstract:

Background: The use of Zoledronic acid (ZA) is an established place in the treatment of malignant tumors with a predilection for the skeleton of interest (in particular metastasis). Although the main target of Zoledronic acid was osteoclasts, there are preclinical data suggest that Zoledronic acid may have an antitumor effect on cells other than osteoclasts, including tumor cells. Antitumor activity, including the inhibition of tumor cell growth and the induction of apoptosis of tumor cells, inhibition of tumor cell adhesion and invasion, and anti-angiogenic effects have been demonstrated. Methods. From (2012 to 2014), 438 patients were included respondents the inclusion criteria, respectively. This is a prospective study over a 4 year period. Of all patients (N=438), 432 received neoadjuvant chemotherapy with Zoledronic acid. The primary end point was the pathologic complete response in advancer breast cancer stage. The secondary end point is to evaluate Clinical response according to RECIST criteria; estimate the bone density before and at the end of chemotherapy in women with locally advanced breast cancer, Toxicity Evaluation and Overall survival using Kaplan-Meier and log test. Result: The Objective response rate was 97% after (C4) with 3% stabilizations and 99, 3% of which 0.7% C8 after stabilization. The clinical complete response was 28% after C4 respectively, and 46.8% after C8, the pathologic complete response rate was 40.13% according to the classification Sataloff. We observed that the pathologic complete response rate was the most raised in the group including Her2 (luminal Her2 and Her2) the lowest in the triple negative group as classified by Sataloff. We found that the pCR is significantly higher in the age group (35-50 years) with 53.17%. Those who have more than 50 years in 2nd place with 27.7% and the lower in young woman 35 years pCR was 19%, not statistically significant, -The pCR was also in favor of the menopausal group in 51, 4%, and 48, 55% for non-menopausal women. The average duration of overall survival was also significantly in the subgroup (Luminal -Her2, Her2) compared with triple negative. It is 47.18 months in the luminal group vs. 38.95 in the triple negative group. -Was observed in our study a difference in quality of life between (C1) was the admission of the patient, and after (C8), we found an increase in general signs and a deterioration in the psychological state C1, in contrast to the C8 these general signs and mental status improves, up to 12, and 24 months. Conclusion The results of this study suggest that the addition of ZA to néoadjuvant CT has potential anti-cancer benefit in patients (Luminal -Her2, Her2) compared with triple negative with or without menopause status.

Keywords: HER2+, RH+, breast cancer, tyrosine kinase

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776 Monte Carlo Pathwise Sensitivities for Barrier Options with Application to Coco-Bond Calibration

Authors: Thomas Gerstner, Bastian von Harrach, Daniel Roth

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The Monte Carlo pathwise sensitivities approach is well established for smooth payoff functions. In this work, we present a new Monte Carlo algorithm that is able to calculate the pathwise sensitivities for discontinuous payoff functions. Our main tool is the one-step survival idea of Glasserman and Staum. Although this technique yields to new terms per observation, while differentiating, the algorithm is still efficient. As an application, we use the results for a two-dimensional calibration of a Coco-Bond, which we model with different types of discretely monitored barrier options.

Keywords: Monte Carlo, discretely monitored barrier options, pathwise sensitivities, Coco-Bond

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775 Plants as Alternative Covers at Contaminated Sites

Authors: M. Grifoni, G. Petruzzelli, M. Barbafieri, I. Rosellini, B. Pezzarossa, F. Pedron

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Evapotranspiration (ET) covers are an alternative cover system that utilizes water balance approach to maximize the ET process to reduce the contaminants leaching through the soil profile. Microcosm tests allow to identify in a short time the most suitable plant species to be used as alternative covers, their survival capacity, and simultaneously the transpiration and evaporation rate of the cover in a specific contaminated soil. This work shows the soil characterization and ET results of microcosm tests carried out on two contaminated soils by using Triticum durum and Helianthus annuus species. The data indicated that transpiration was higher than evaporation, supporting the use of plants as alternative cover at this contaminated site.

Keywords: contaminated sites, evapotranspiration cover, evapotranspiration, microcosm experiments

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774 Design of 100 kW Induction Generator for Wind Power Plant at Tamanjaya Village-Sukabumi

Authors: Andri Setiyoso, Agus Purwadi, Nanda Avianto Wicaksono

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This paper present about induction generator design for 100kW power output capacity. Induction machine had been chosen because of the capability for energy conversion from electric energy to mechanical energy and vise-versa with operation on variable speed condition. Stator Controlled Induction Generator (SCIG) was applied as wind power plant in Desa Taman Jaya, Sukabumi, Indonesia. Generator was designed to generate power 100 kW with wind speed at 12 m/s and survival condition at speed 21 m/s.

Keywords: wind energy, induction generator, Stator Controlled Induction Generator (SCIG), variable speed generator

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773 A Call for Justice and a New Economic Paradigm: Analyzing Counterhegemonic Discourses for Indigenous Peoples' Rights and Environmental Protection in Philippine Alternative Media

Authors: B. F. Espiritu

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This paper examines the resistance of the Lumad people, the indigenous peoples in Mindanao, Southern Philippines, and of environmental and human rights activists to the Philippine government's neoliberal policies and their call for justice and a new economic paradigm that will uphold peoples' rights and environmental protection in two alternative media online sites. The study contributes to the body of knowledge on indigenous resistance to neoliberal globalization and the quest for a new economic paradigm that upholds social justice for the marginalized in society, empathy and compassion for those who depend on the land for their survival, and environmental sustainability. The study analyzes the discourses in selected news articles from Davao Today and Kalikasan (translated to English as 'Nature') People's Network for the Environment’s statements and advocacy articles for the Lumad and the environment from 2018 to February 2020. The study reveals that the alternative media news articles and the advocacy articles contain statements that expose the oppression and violation of human rights of the Lumad people, farmers, government environmental workers, and environmental activists as shown in their killings, illegal arrest and detention, displacement of the indigenous peoples, destruction of their schools by the military and paramilitary groups, and environmental plunder and destruction with the government's permit for the entry and operation of extractive and agribusiness industries in the Lumad ancestral lands. Anchored on Christian Fuch's theory of alternative media as critical media and Bert Cammaerts' theorization of alternative media as counterhegemonic media that are part of civil society and form a third voice between state media and commercial media, the study reveals the counterhegemonic discourses of the news and advocacy articles that oppose the dominant economic system of neoliberalism which oppresses the people who depend on the land for their survival. Furthermore, the news and advocacy articles seek to advance social struggles that transform society towards the realization of cooperative potentials or a new economic paradigm that upholds economic democracy, where the local people, including the indigenous people, are economically empowered their environment and protected towards the realization of self-sustaining communities. The study highlights the call for justice, empathy, and compassion for both the people and the environment and the need for a new economic paradigm wherein indigenous peoples and local communities are empowered towards becoming self-sustaining communities in a sustainable environment.

Keywords: alternative media, environmental sustainability, human rights, indigenous resistance

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772 The Chemistry in the Video Game No Man’s Sky

Authors: Diogo Santos, Nelson Zagalo, Carla Morais

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No Man’s Sky (NMS) is a sci-fi video game about survival and exploration where players fly spaceships, search for elements, and use them to survive. NMS isn’t a serious game, and not all the science in the game is presented with scientific evidence. To find how players felt about the scientific content in the game and how they perceive the chemistry in it, a survey was sent to NMS’s players, from which were collected answers from 124 respondents from 23 countries. Chemophobia is still a phenomenon when chemistry or chemicals are a subject of discussion, but 68,9% of our respondents showed a positive attitude towards the presence of chemistry in NMS, with 57% stating that playing the video game motivated them to know more about science. 8% of the players stated that NMS often prompted conversations about the science in the video game between them and teachers, parents, or friends. These results give us ideas on how an entertainment game can potentially help scientists, educators, and science communicators reach a growing, evolving, vibrant, diverse, and demanding audience.

Keywords: digital games, science communication, chemistry, informal learning, No Man’s Sky

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771 Development of Enhanced Data Encryption Standard

Authors: Benjamin Okike

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There is a need to hide information along the superhighway. Today, information relating to the survival of individuals, organizations, or government agencies is transmitted from one point to another. Adversaries are always on the watch along the superhighway to intercept any information that would enable them to inflict psychological ‘injuries’ to their victims. But with information encryption, this can be prevented completely or at worst reduced to the barest minimum. There is no doubt that so many encryption techniques have been proposed, and some of them are already being implemented. However, adversaries always discover loopholes on them to perpetuate their evil plans. In this work, we propose the enhanced data encryption standard (EDES) that would deploy randomly generated numbers as an encryption method. Each time encryption is to be carried out, a new set of random numbers would be generated, thereby making it almost impossible for cryptanalysts to decrypt any information encrypted with this newly proposed method.

Keywords: encryption, enhanced data encryption, encryption techniques, information security

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770 Low SPOP Expression and High MDM2 expression Are Associated with Tumor Progression and Predict Poor Prognosis in Hepatocellular Carcinoma

Authors: Chang Liang, Weizhi Gong, Yan Zhang

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Purpose: Hepatocellular carcinoma (HCC) is a malignant tumor with a high mortality rate and poor prognosis worldwide. Murine double minute 2 (MDM2) regulates the tumor suppressor p53, increasing cancer risk and accelerating tumor progression. Speckle-type POX virus and zinc finger protein (SPOP), a key of subunit of Cullin-Ring E3 ligase, inhibits tumor genesis and progression by the ubiquitination of its downstream substrates. This study aimed to clarify whether SPOP and MDM2 are mutually regulated in HCC and the correlation between SPOP and MDM2 and the prognosis of HCC patients. Methods: First, the expression of SPOP and MDM2 in HCC tissues were detected by TCGA database. Then, 53 paired samples of HCC tumor and adjacent tissues were collected to evaluate the expression of SPOP and MDM2 using immunohistochemistry. Chi-square test or Fisher’s exact test were used to analyze the relationship between clinicopathological features and the expression levels of SPOP and MDM2. In addition, Kaplan‒Meier curve analysis and log-rank test were used to investigate the effects of SPOP and MDM2 on the survival of HCC patients. Last, the Multivariate Cox proportional risk regression model analyzed whether the different expression levels of SPOP and MDM2 were independent risk factors for the prognosis of HCC patients. Results: Bioinformatics analysis revealed the low expression of SPOP and high expression of MDM2 were related to worse prognosis of HCC patients. The relationship between the expression of SPOP and MDM2 and tumor stem-like features showed an opposite trend. The immunohistochemistry showed the expression of SPOP protein was significantly downregulated while MDM2 protein significantly upregulated in HCC tissue compared to that in para-cancerous tissue. Tumors with low SPOP expression were related to worse T stage and Barcelona Clinic Liver Cancer (BCLC) stage, but tumors with high MDM2 expression were related to worse T stage, M stage, and BCLC stage. Kaplan–Meier curves showed HCC patients with high SPOP expression and low MDM2 expression had better survival than those with low SPOP expression and high MDM2 expression (P < 0.05). A multivariate Cox proportional risk regression model confirmed that a high MDM2 expression level was an independent risk factor for poor prognosis in HCC patients (P <0.05). Conclusion: The expression of SPOP protein was significantly downregulated, while the expression of MDM2 significantly upregulated in HCC. The low expression of SPOP and high expression. of MDM2 were associated with malignant progression and poor prognosis of HCC patients, indicating a potential therapeutic target for HCC patients.

Keywords: hepatocellular carcinoma, murine double minute 2, speckle-type POX virus and zinc finger protein, ubiquitination

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769 iPSC-derived MSC Mediated Immunosuppression during Mouse Airway Transplantation

Authors: Mohammad Afzal Khan, Fatimah Alanazi, Hala Abdalrahman Ahmed, Talal Shamma, Kilian Kelly, Mohammed A. Hammad, Abdullah O. Alawad, Abdullah Mohammed Assiri, Dieter Clemens Broering

Abstract:

Lung transplantation is a life-saving surgical replacement of diseased lungs in patients with end-stage respiratory malfunctions. Despite the remarkable short-term recovery, long-term lung survival continues to face several significant challenges, including chronic rejection and severe toxic side-effects due to global immunosuppression. Stem cell-based immunotherapy has been recognized as a crucial immunoregulatory regimen in various preclinical and clinical studies. Despite initial therapeutic outcomes, conventional stem cells face key limitations. The Cymerus™ manufacturing facilitates the production of a virtually limitless supply of consistent human induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells, which could play a key role in selective immunosuppression and graft repair during rejection. Here, we demonstrated the impact of iPSC-derived human MSCs on the development of immune-tolerance and long-term graft survival in mouse orthotopic airway allografts. BALB/c→C57BL/6 allografts were reconstituted with iPSC-derived MSCs (2 million/transplant/ at d0), and allografts were examined for regulatory T cells (Tregs), oxygenation, microvascular blood flow, airway epithelium and collagen deposition during rejection. We demonstrated that iPSC-derived MSC treatment leads to significant increase in tissue expression of hTSG-6 protein, followed by an upregulation of mouse Tregs and IL-5, IL-10, IL-15 cytokines, which augments graft microvascular blood flow and oxygenation, and thereby maintained a healthy airway epithelium and prevented the subepithelial deposition of collagen at d90 post-transplantation. Collectively, these data confirmed that iPSC-derived MSC-mediated immunosuppression has potential to establish immune-tolerance and rescue allograft from sustained hypoxic/ischemic phase and subsequently limits long-term airway epithelial injury and collagen progression, which therapeutically warrant a study of Cymerus iPSC-derived MSCs as a potential management option for immunosuppression in transplant recipients.

Keywords: stem cell therapy, immunotolerance, regulatory T cells, hypoxia and ischemia, microvasculature

Procedia PDF Downloads 158
768 Evaluation of Radioprotective Effect of Solanun melongena L. in the Survival of Lasioderma serricorne (Coleoptera, Anobiidae) Irradiated with Gamma Rays of Cobalt-60

Authors: Adilson C. Barros, Kayo Okazaki, Valter Arthur

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The radio-protective substances protect the organism from ionizing radiation when previously ingested. Synthetic radio-protectives produce unpleasant side effects and are expensive. This article reports the search for natural radio-protective agents in foods, whose occurrence is widespread, costs are lower and the side effects are non-existent. In this work, we studied the eggplant, a food widely used in Brazil, comparing the radiosensitivity of insects reared on diet eggplant and outside this diet. The eggplant causes change in LD50 parameter of insects population but the response curve needs to be better shaped to conclude something about radioprotection. What we can see is that it seems to contain some radiomodifier substance.

Keywords: radioprotector, radiobiology, Solanun melongena L., Lasioderma serricorne

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767 Strategic Planning in South African Higher Education

Authors: Noxolo Mafu

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This study presents an overview of strategic planning in South African higher education institutions by tracing its trends and mystique in order to identify its impact. Over the democratic decades, strategic planning has become integral to institutional survival. It has been used as a potent tool by several institutions to catch up and surpass counterparts. While planning has always been part of higher education, strategic planning should be considered different. Strategic planning is primarily about development and maintenance of a strategic fitting between an institution and its dynamic opportunities. This presupposes existence of sets of stages that institutions pursue of which, can be regarded for assessment of the impact of strategic planning in an institution. The network theory serves guides the study in demystifying apparent organisational networks in strategic planning processes.

Keywords: network theory, strategy, planning, strategic planning, assessment, impact

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766 Evaluation of Aggregate Risks in Sustainable Manufacturing Using Fuzzy Multiple Attribute Decision Making

Authors: Gopinath Rathod, Vinod Puranik

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Sustainability is regarded as a key concept for survival in the competitive scenario. Industrial risk and diversification of risk type’s increases with industrial developments. In the context of sustainable manufacturing, the evaluation of risk is difficult because of the incomplete information and multiple indicators. Fuzzy Multiple Attribute Decision Method (FMADM) has been used with a three level hierarchical decision making model to evaluate aggregate risk for sustainable manufacturing projects. A case study has been presented to reflect the risk characteristics in sustainable manufacturing projects.

Keywords: sustainable manufacturing, decision making, aggregate risk, fuzzy logic, fuzzy multiple attribute decision method

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765 Reproduction Characteristics of Saanen Goats Raised under Intensive Conditions in Konya Province

Authors: Vahdettin Sariyel, Birol Dag

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In this research, it is aimed to determine the effects of several environmental factors on adaptation and some yield parameters of Saanen goats reared under intensive conditions at a private farm in Konya province. Gestation rate, twins rate and litter size were evaluated as reproductive traits. Gestation rate was determined as 93.8% and 90.5% for 2011 and 2012 years respectively. Twins rate was determined as 59.35 % and 70.00 % for 2011 and 2012 years respectively. Litter size was 1.49 and 1.46 for 2011 and 2012 years respectively. Survival rates of kids from birth to weaning at three months of age were found as 87.74 % and 98.54 % for 2011 and 2012 years respectively.

Keywords: gestation rate, reproduction, saanen, twins rate, vitality

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764 Monoallelic and Biallelic Deletions of 13q14 in a Group of 36 CLL Patients Investigated by CGH Haematological Cancer and SNP Array (8x60K)

Authors: B. Grygalewicz, R. Woroniecka, J. Rygier, K. Borkowska, A. Labak, B. Nowakowska, B. Pienkowska-Grela

Abstract:

Introduction: Chronic lymphocytic leukemia (CLL) is the most common form of adult leukemia in the Western world. Hemizygous and or homozygous loss at 13q14 occur in more than half of cases and constitute the most frequent chromosomal abnormality in CLL. It is believed that deletions 13q14 play a role in CLL pathogenesis. Two microRNA genes miR-15a and miR- 16-1 are targets of 13q14 deletions and plays a tumor suppressor role by targeting antiapoptotic BCL2 gene. Deletion size, as a single change detected in FISH analysis, has haprognostic significance. Patients with small deletions, without RB1 gene involvement, have the best prognosis and the longest overall survival time (OS 133 months). In patients with bigger deletion region, containing RB1 gene, prognosis drops to intermediate, like in patients with normal karyotype and without changes in FISH with overall survival 111 months. Aim: Precise delineation of 13q14 deletions regions in two groups of CLL patients, with mono- and biallelic deletions and qualifications of their prognostic significance. Methods: Detection of 13q14 deletions was performed by FISH analysis with CLL probe panel (D13S319, LAMP1, TP53, ATM, CEP-12). Accurate deletion size detection was performed by CGH Haematological Cancer and SNP array (8x60K). Results: Our investigated group of CLL patients with the 13q14 deletion, detected by FISH analysis, comprised two groups: 18 patients with monoallelic deletions and 18 patients with biallelic deletions. In FISH analysis, in the monoallelic group the range of cells with deletion, was 43% to 97%, while in biallelic group deletion was detected in 11% to 94% of cells. Microarray analysis revealed precise deletion regions. In the monoallelic group, the range of size was 348,12 Kb to 34,82 Mb, with median deletion size 7,93 Mb. In biallelic group discrepancy of total deletions, size was 135,27 Kb to 33,33 Mb, with median deletion size 2,52 Mb. The median size of smaller deletion regions on one copy chromosome 13 was 1,08 Mb while the average region of bigger deletion on the second chromosome 13 was 4,04 Mb. In the monoallelic group, in 8/18 deletion region covered RB1 gene. In the biallelic group, in 4/18 cases, revealed deletion on one copy of biallelic deletion and in 2/18 showed deletion of RB1 gene on both deleted 13q14 regions. All minimal deleted regions included miR-15a and miR-16-1 genes. Genetic results will be correlated with clinical data. Conclusions: Application of CGH microarrays technique in CLL allows accurately delineate the size of 13q14 deletion regions, what have a prognostic value. All deleted regions included miR15a and miR-16-1, what confirms the essential role of these genes in CLL pathogenesis. In our investigated groups of CLL patients with mono- and biallelic 13q14 deletions, patients with biallelic deletion presented smaller deletion sizes (2,52 Mb vs 7,93 Mb), what is connected with better prognosis.

Keywords: CLL, deletion 13q14, CGH microarrays, SNP array

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763 Micropropagation of Pelargonium odoratissimum (L.) L’Her., Using Petiole and Leaf Explants

Authors: Mohammad Ali Aazami Mavaloo, Mohammad Bagher Hassanpouraghdam

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Intact leaves, leaf segments and petiole sections derived from nodal explants in vitro were employed for the optimization of Pelargonium odoratissimum micropropagation. MS and ½ MS media enriched with BAP (1, 1.5, 2 and 4.5 mg/l) and NAA (0.1, 1 and 1.5 mg/l) were the treatment combinations used for. With leaf segments, the lowest browning incidence, the greatest callogenesis and the highest number of shoots were obtained with the media containing 1.5 mg/L BAP and 1 mg/L NAA. Two mg/L BAP + 0.1 mg/L NAA hold the same results for petiole explants. Intact leaves showed the best results for the three before-mentioned traits with 1 mg/L BAP + 1 mg/L NAA. 0.2 mg/L NAA caused the highest rooting percentage and the greatest mean data for the number and length of the roots. Rooted plantlets were transferred to the pots containing 1:1 peat-moss and perlite. Acclimatization of the plantlets was followed by 90 percent of survival rate in the greenhouse.

Keywords: Pelargonium odoratissimum, micropropagation, BAP, NAA

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762 Decision Location and Resource Requirement for Relief Goods Assembly

Authors: Glenda B. Minguito, Jenith L. Banluta

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One of the critical aspects of humanitarian operations is the distribution of relief goods to the affected community. The common assumption is that relief goods are prepositioned during disasters which are not applicable in developing countries like the Philippines. During disasters, the on-the-ground government agencies and responders have to procure, sort, weigh and pack the relief goods. There is a need to review the relief goods preparation as it seriously affects the delivery of necessary aid for human survival. This study also identifies the ideal location of the assembly hub to minimize the distance to the affected community. This paper reveals that location and resources are dependent on the type of disasters encountered at the local level. The Center-of-Gravity method and Multiple Activity Chart were applied in the analysis.

Keywords: humanitarian supply chain, location decision, resource allocation, local level

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761 Nematodes, Rotifers, Tardigrades and Diatoms as Vehicles for the Panspermic Transfer of Microbes

Authors: Sulamain Alharbi, Mohammad Khiyami, Reda Amasha, Bassam Al-Johny, Hesham Khalil, Milton Wainwrigh

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Nematodes, Rotifers and Tardigrades (NRT) are extreme-tolerant invertebrates which can survive long periods of stasis brought about by extreme drying and cold. They can also resist the effects of UV radiation, and as a result could act as vehicles for the panspermic transfer of microorganisms. Here we show that NRT contain a variety of bacteria and fungi within their bodies in which environment they could be protected from the extremes of the space and released into new cosmic environments. Diatoms were also shown to contain viable alga and Escherichia coli and so could also act as panspermic vehicles for the transfer of these and perhaps other microbes through space. Although not studied here, NRT, and possibly diatoms, also carry protozoa and viruses within their bodies and could act as vehicles for the panspermic transfer of an even wider range of microbes than shown here.

Keywords: extromophiles, diatoms, panspermia, survival in space

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760 Predictors for Success in Methadone Maintenance Treatment Clinic: 24 Years of Experience

Authors: Einat E. Peles, Shaul Schreiber, Miriam Adelson

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Background: Since established more than 50 years ago, methadone maintenance treatment (MMT) is the most effective treatment for opioid addiction, a chronic relapsing brain disorder that became an epidemic in western societies. Treatment includes daily individual optimal medication methadone dose (a long acting mu opioid receptor full agonist), accompanied with psychosocial therapy. It is well established that the longer retention in treatment the better outcome and survival occur. It reduces the likelihood to infectious diseases and overdose death that associated with drug injecting, enhanced social rehabilitation and eliminate criminal activity, and lead to healthy productive life. Aim: To evaluate predictors for long term retention in treatment we analyzed our prospective follow up of a major MMT clinic affiliated to a big tertiary medical center. Population Methods: Between June 25, 1993, and June 24, 2016, all 889 patients ( ≥ 18y) who ever admitted to the clinic were prospectively followed-up until May 2017. Duration in treatment from the first admission until the patient quit treatment or until the end of follow-up (24 years) was taken for calculating cumulative retention in treatment using survival analyses (Kaplan Meier) with log-rank and Cox regression for multivariate analyses. Results: Of the 889 patients, 25.2% were females who admitted to treatment at younger age (35.0 ± 7.9 vs. 40.6 ± 9.8, p < .0005), but started opioid usage at same age (22.3 ± 6.9). In addition to opioid use, on admission to MMT 58.5% had positive urine for benzodiazepines, 25% to cocaine, 12.4% to cannabis and 6.9% to amphetamines. Hepatitis C antibody tested positive in 55%, and HIV in 7.8% of the patients and 40%. Of all patients, 75.7% stayed at least one year in treatment, and of them, 67.7% stopped opioid usage (based on urine tests), and a net reduction observed in all other substance abuse (proportion of those who stopped minus proportion of those who have started). Long term retention up to 24 years was 8.0 years (95% Confidence Interval (CI) 7.4-8.6). Predictors for longer retention in treatment (Cox regression) were being older on admission ( ≥ 30y) Odds Ratio (OR) =1.4 (CI 1.1-1.8), not abusing opioids after one year OR=1.8 (CI 1.5-2.1), not abusing benzodiazepine after one year OR=1.7 (CI 1.4-2.1) and treating with methadone dose ≥ 100mg/day OR =1.8 (CI 1.5-2.3). Conclusions: Treating and following patients over 24 years indicate success of two main outcomes, high rate of retention after one year (75.7%) and high proportion of opiate abuse cessation (67.7%). As expected, longer cumulative retention was associated with patients treated with high adequate methadone dose that successfully result in opioid cessation. Based on these findings, in order to reduce morbidity and mortality, we find the establishment of more MMT clinics within a general hospital, a most urgent necessity.

Keywords: methadone maintenance treatment, epidemic, opioids, retention

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759 Curcumin Nanomedicine: A Breakthrough Approach for Enhanced Lung Cancer Therapy

Authors: Shiva Shakori Poshteh

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Lung cancer is a highly prevalent and devastating disease, representing a significant global health concern with profound implications for healthcare systems and society. Its high incidence, mortality rates, and late-stage diagnosis contribute to its formidable nature. To address these challenges, nanoparticle-based drug delivery has emerged as a promising therapeutic strategy. Curcumin (CUR), a natural compound derived from turmeric, has garnered attention as a potential nanomedicine for lung cancer treatment. Nanoparticle formulations of CUR offer several advantages, including improved drug delivery efficiency, enhanced stability, controlled release kinetics, and targeted delivery to lung cancer cells. CUR exhibits a diverse array of effects on cancer cells. It induces apoptosis by upregulating pro-apoptotic proteins, such as Bax and Bak, and downregulating anti-apoptotic proteins, such as Bcl-2. Additionally, CUR inhibits cell proliferation by modulating key signaling pathways involved in cancer progression. It suppresses the PI3K/Akt pathway, crucial for cell survival and growth, and attenuates the mTOR pathway, which regulates protein synthesis and cell proliferation. CUR also interferes with the MAPK pathway, which controls cell proliferation and survival, and modulates the Wnt/β-catenin pathway, which plays a role in cell proliferation and tumor development. Moreover, CUR exhibits potent antioxidant activity, reducing oxidative stress and protecting cells from DNA damage. Utilizing CUR as a standalone treatment is limited by poor bioavailability, lack of targeting, and degradation susceptibility. Nanoparticle-based delivery systems can overcome these challenges. They enhance CUR’s bioavailability, protect it from degradation, and improve absorption. Further, Nanoparticles enable targeted delivery to lung cancer cells through surface modifications or ligand-based targeting, ensuring sustained release of CUR to prolong therapeutic effects, reduce administration frequency, and facilitate penetration through the tumor microenvironment, thereby enhancing CUR’s access to cancer cells. Thus, nanoparticle-based CUR delivery systems promise to improve lung cancer treatment outcomes. This article provides an overview of lung cancer, explores CUR nanoparticles as a treatment approach, discusses the benefits and challenges of nanoparticle-based drug delivery, and highlights prospects for CUR nanoparticles in lung cancer treatment. Future research aims to optimize these delivery systems for improved efficacy and patient prognosis in lung cancer.

Keywords: lung cancer, curcumin, nanomedicine, nanoparticle-based drug delivery

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758 Corporate Law and Its View Point of Locking in Capital

Authors: Saad Saeed Althiabi

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This paper discusses the corporate positioning and how it became popular as a way to systematize production because of the unique manner in which incorporation legalized organizers to secure financial capital through locking it in. The power to lock in capital comes from the fact that a corporate exists as a separate legal entity, whose survival and governance are separated from any of its participants. The law essentially creates a different legal person when a corporation is created. Although this idea has been played down in the legal learning of the last decades in favor of the view that a corporation is purely something through which natural persons interrelate, recent legal research has begun to reassess the importance of entity status. Entity status, under the law and the related separation of governance from input of financial capital through the configuration of a corporation, sanctioned corporate participants to do somewhat more than connect in a series of business transactions.

Keywords: corporate law, entity status, locking in capital, financial capital

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757 A Comparative Study of Maternal Health among Urban Slums and Non-Slums Women (Special Reference to Indore City, Madhya Pradesh, India)

Authors: Shiksha Thakur, Rashmi Jain

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Maternal health is the most crucial element in the primary health care delivery system of any healthy society. We aware that the maternal health situation in India has been a cause of concern for us, in spite of the rapidly progressing socio-economic environment overall. India has realized impressive gains in Mother & Child survival over the last two decades. MMR as per 2012-2013 in India is 167 as per MMR bulletin, though there are variations between states in the Country. In 2013, an estimated 2,89,000 women worldwide died from complications arising from pregnancy & childbirth. In view of the above facts, a study was conducted in Indore to analyse the maternal health status among urban slums and non-slums women.

Keywords: antenatal care, postnatal care, JSY, maternal health, child health, reproductive health

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756 Different Response of Pure Arctic Char Salvelinus alpinus and Hybrid (Salvelinus alpinus vs. Salvelinus fontinalis Mitchill) to Various Hyperoxic Regimes

Authors: V. Stejskal, K. Lundova, R. Sebesta, T. Vanina, S. Roje

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Pure strain of Arctic char (AC) Salvelinus alpinus and hybrid (HB) Salvelinus alpinus vs. Salvelinus fontinalis Mitchill belong to fish, which with great potential for culture in recirculating aquaculture systems (RAS). Aquaculture of these fish currently use flow-through systems (FTS), especially in Nordic countries such as Iceland (biggest producer), Norway, Sweden, and Canada. Four different water saturation regimes included normoxia (NOR), permanent hyperoxia (HYP), intermittent hyperoxia (HYP ± ) and regimes where one day of normoxia was followed by one day of hyperoxia (HYP1/1) were tested during 63 days of experiment in both species in two parallel experiments. Fish were reared in two identical RAS system consisted of 24 plastic round tanks (300 L each), drum filter, biological filter with moving beads and submerged biofilter. The temperature was maintained using flow-through cooler during at level of 13.6 ± 0.8 °C. Different water saturation regimes were achieved by mixing of pure oxygen (O₂) with water in three (one for each hyperoxic regime) mixing tower equipped with flowmeter for regulation of gas inflow. The water in groups HYP, HYP1/1 and HYP± was enriched with oxygen up to saturation of 120-130%. In HYP group was this level kept during whole day. In HYP ± group was hyperoxia kept for daylight phase (08:00-20:00) only and during night time was applied normoxia in this group. The oxygen saturation of 80-90% in NOR group was created using intensive aeration in header tank. The fish were fed with commercial feed to slight excess at 2 h intervals within the light phase of the day. Water quality parameters like pH, temperature and level of oxygen was monitoring three times (7 am, 10 am and 6 pm) per day using handy multimeter. Ammonium, nitrite and nitrate were measured in two day interval using spectrophotometry. Initial body weight (BW) was 40.9 ± 8.7 g and 70.6 ± 14.8 in AC and HB group, respectively. Final survival of AC ranged from 96.3 ± 4.6 (HYP) to 100 ± 0.0% in all other groups without significant differences among these groups. Similarly very high survival was reached in trial with HB with levels from 99.2 ± 1.3 (HYP, HYP1/1 and NOR) to 100 ± 0.0% (HYP ± ). HB fish showed best growth performance in NOR group reached final body weight (BW) 180.4 ± 2.3 g. Fish growth under different hyperoxic regimes was significantly reduced and final BW was 164.4 ± 7.6, 162.1 ± 12.2 and 151.7 ± 6.8 g in groups HY1/1, HYP ± and HYP, respectively. AC showed different preference for hyperoxic regimes as there were no significant difference in BW among NOR, HY1/1 and HYP± group with final values of 72.3 ± 11.3, 68.3 ± 8.4 and 77.1 ± 6.1g. Significantly reduced growth (BW 61.8 ± 6.8 g) was observed in HYP group. It is evident from present study that there are differences between pure bred Arctic char and hybrid in relation to hyperoxic regimes. The study was supported by projects 'CENAKVA' (No. CZ.1.05/2.1.00/01.0024), 'CENAKVA II' (No. LO1205 under the NPU I program), NAZV (QJ1510077) and GAJU (No. 060/2016/Z).

Keywords: recirculating aquaculture systems, Salmonidae, hyperoxia, abiotic factors

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755 New Media Impact on Newspaper Readership

Authors: Umar Lawal Maradun

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Newspapers are very important sources of information and are trusted by majority of populations in America, Latin America, Europe and many parts of the world. In the mid-1950s newspapers were at the forefront of providing people with information. However, in the 1970s television took over, while in the 1980s cable satellites became popular and in the 1990s the Internet and World Wide Web became major sources of media content and also major threats to the print media form. This paper looks at how newspaper readership has been affected by new media technology, especially the Internet. It uses empirical data by reviewing available literature within the context of change that is likely to threaten conventional media. It discovers that there is a growing decline in newspaper readership as a result of widespread use of the Internet. The decline in readership has been discovered to be a global phenomenon. The paper suggests strategies for the survival and revenue generation for print-based newspapers.

Keywords: Internet, media, newspaper, press

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754 Working Capital Management Practices in Small Businesses in Victoria

Authors: Ranjith Ihalanayake, Lalith Seelanatha, John Breen

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In this study, we explored the current working capital management practices as applied in small businesses in Victoria, filling an existing theoretical and empirical gap in literature in general and in Australia in particular. Amidst the current global competitive and dynamic environment, the short term insolvency of small businesses is very critical for the long run survival. A firm’s short-term insolvency is dependent on the availability of sufficient working capital for feeding day to day operational activities. Therefore, given the reliance for short-term funding by small businesses, it has been recognized that the efficient management of working capital is crucial in respect of the prosperity and survival of such firms. Against this background, this research was an attempt to understand the current working capital management strategies and practices used by the small scale businesses. To this end, we conducted an internet survey among 220 small businesses operating in Victoria, Australia. The survey results suggest that the majority of respondents are owner-manager (73%) and male (68%). Respondents participated in this survey mostly have a degree (46%). About a half of respondents are more than 50 years old. Most of respondents (64%) have business management experience more than ten years. Similarly, majority of them (63%) had experience in the area of their current business. Types of business of the respondents are: Private limited company (41%), sole proprietorship (37%), and partnership (15%). In addition, majority of the firms are service companies (63%), followed by retailed companies (25%), and manufacturing (17%). Size of companies of this survey varies, 32% of them have annual sales $100,000 or under, while 22% of them have revenue more than $1,000,000 every year. In regards to the total assets, majority of respondents (43%) have total assets $100,000 or less while 20% of respondents have total assets more than $1,000,000. In regards to WCMPs, results indicate that almost 70% of respondents mentioned that they are responsible for managing their business working capital. The survey shows that majority of respondents (65.5%) use their business experience to identify the level of investment in working capital, compared to 22% of respondents who seek advice from professionals. The other 10% of respondents, however, follow industry practice to identify the level of working capital. The survey also shows that more than a half of respondents maintain good liquidity financial position for their business by having accounts payable less than accounts receivable. This study finds that majority of small business companies in western area of Victoria have a WCM policy but only about 8 % of them have a formal policy. Majority of the businesses (52.7%) have an informal policy while 39.5% have no policy. Of those who have a policy, 44% described their working capital management policies as a compromise policy while 35% described their policy as a conservative policy. Only 6% of respondents apply aggressive policy. Overall the results indicate that the small businesses pay less attention into the management of working capital of their business despite its significance in the successful operation of the business. This approach may be adopted during favourable economic times. However, during relatively turbulent economic conditions, such an approach could lead to greater financial difficulties i.e. short-term financial insolvency.

Keywords: small business, working capital management, Australia, sufficient, financial insolvency

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753 Investigating the Use of Advanced Manufacturing Technologies in the Assembly Type Manufacturing Companies in Trinidad and Tobago

Authors: Nadine Sangster, Akil James, Rondell Duke, Aaron Ameerali, Terrence Lalla

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The market place of the 21st century is evolving into one of merging national markets, fragmented consumer markets, and rapidly changing product technologies. The use of new technologies has become vital to the manufacturing industry for their survival and sustainability. This work focused on the assembly type industry in a small developing country and aimed at identifying the use of advanced manufacturing technologies and their impact on this sector of the manufacturing industry. It was found that some technologies were being used and that they had improved the effectiveness of those companies but there was still quite a bit of room for improvements. Some of the recommendations included benchmarking against international standards, the adoption of a “made in TT” campaign and the effective utilisation of the technologies to improve manufacturing effectiveness and thus improve competitive advantages and strategies.

Keywords: advanced manufacturing technology, Trinidad and Tobago, manufacturing, industrial engineering

Procedia PDF Downloads 493
752 Evolutionary Advantages of Loneliness with an Agent-Based Model

Authors: David Gottlieb, Jason Yoder

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The feeling of loneliness is not uncommon in modern society, and yet, there is a fundamental lack of understanding in its origins and purpose in nature. One interpretation of loneliness is that it is a subjective experience that punishes a lack of social behavior, and thus its emergence in human evolution is seemingly tied to the survival of early human tribes. Still, a common counterintuitive response to loneliness is a state of hypervigilance, resulting in social withdrawal, which may appear maladaptive to modern society. So far, no computational model of loneliness’ effect during evolution yet exists; however, agent-based models (ABM) can be used to investigate social behavior, and applying evolution to agents’ behaviors can demonstrate selective advantages for particular behaviors. We propose an ABM where each agent contains four social behaviors, and one goal-seeking behavior, letting evolution select the best behavioral patterns for resource allocation. In our paper, we use an algorithm similar to the boid model to guide the behavior of agents, but expand the set of rules that govern their behavior. While we use cohesion, separation, and alignment for simple social movement, our expanded model adds goal-oriented behavior, which is inspired by particle swarm optimization, such that agents move relative to their personal best position. Since agents are given the ability to form connections by interacting with each other, our final behavior guides agent movement toward its social connections. Finally, we introduce a mechanism to represent a state of loneliness, which engages when an agent's perceived social involvement does not meet its expected social involvement. This enables us to investigate a minimal model of loneliness, and using evolution we attempt to elucidate its value in human survival. Agents are placed in an environment in which they must acquire resources, as their fitness is based on the total resource collected. With these rules in place, we are able to run evolution under various conditions, including resource-rich environments, and when disease is present. Our simulations indicate that there is strong selection pressure for social behavior under circumstances where there is a clear discrepancy between initial resource locations, and against social behavior when disease is present, mirroring hypervigilance. This not only provides an explanation for the emergence of loneliness, but also reflects the diversity of response to loneliness in the real world. In addition, there is evidence of a richness of social behavior when loneliness was present. By introducing just two resource locations, we observed a divergence in social motivation after agents became lonely, where one agent learned to move to the other, who was in a better resource position. The results and ongoing work from this project show that it is possible to glean insight into the evolutionary advantages of even simple mechanisms of loneliness. The model we developed has produced unexpected results and has led to more questions, such as the impact loneliness would have at a larger scale, or the effect of creating a set of rules governing interaction beyond adjacency.

Keywords: agent-based, behavior, evolution, loneliness, social

Procedia PDF Downloads 97