Search results for: drug policy

Authors: Shan-Ying Wu, Sheng-Hui Lan, Xi-Zhang Lin, Ih-Jen Su, Ting-Fen Tsai, Chia-Jui Yen, Tsung-Hsueh Lu, Fu-Wen Liang, Huey-Jen Su, Chun-Li Su, Hsiao-Sheng Liu

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In hepatocelluar carcinoma (HCC), dysregulated expression of cyclin D1 and impaired autophagy has been reported separately. However, the relationship between them has not been explored. In this study, we demonstrated that autophagy was inversely correlated with cyclin D1 expression in 147 paired HCC patient specimens. HCC specimen with highly expression of cyclin D1 shows correlation with poor overall survival rate. Furthermore, induction of autophagy by amiodarone (antiarrhythmic drug) in Hep 3B cells, cyclin D1 was recruited into autophagosomes demonstrated by immune-gold labeling of cyclin D1 after extraction of autophagosomes. We further demonstrated that autophagy suppresses Hep 3B cell proliferation, and further analysis revealed that cell cycle was arrested at G1 phase. The interaction between LC3 (maker of autophagy) and cyclin D1 was increased after autophagy induction. In addition, ubiquitinated-cyclin D1 was also increased after autophagy induction, which is selectively degraded by autophagosome through binding with SQSTM1/p62 (an adaptor protein). In vivo study showed that amiodarone induced autophagy suppresses liver tumor formation in xenograft mouse and orthotopic rat model through decreasing cyclin D1 expression and inhibition of cell proliferation. Altogether, we reveal a novel mechanism that ubiquitinated cyclin D1 degraded by autophagic pathway by p62 and amiodarone is a promising drug for targeting cyclin D1 in liver cancer therapy.

Keywords: autophagy, cyclin D1, hepatocellular carcinoma, amiodarone

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Authors: Zheni S. Stefanova, Kandethody M. Ramachandran

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With the increasing dependency on our computer devices, we face the necessity of adequate, efficient and effective mechanisms, for protecting our network. There are two main problems that Intrusion Detection Systems (IDS) attempt to solve. 1) To detect the attack, by analyzing the incoming traffic and inspect the network (intrusion detection). 2) To produce a prompt response when the attack occurs (intrusion prevention). It is critical creating an Intrusion detection model that will detect a breach in the system on time and also challenging making it provide an automatic and with an acceptable delay response at every single stage of the monitoring process. We cannot afford to adopt security measures with a high exploiting computational power, and we are not able to accept a mechanism that will react with a delay. In this paper, we will propose an intrusion response mechanism that is based on artificial intelligence, and more precisely, reinforcement learning techniques (RLT). The RLT will help us to create a decision agent, who will control the process of interacting with the undetermined environment. The goal is to find an optimal policy, which will represent the intrusion response, therefore, to solve the Reinforcement learning problem, using a Q-learning approach. Our agent will produce an optimal immediate response, in the process of evaluating the network traffic.This Q-learning approach will establish the balance between exploration and exploitation and provide a unique, self-learning and strategic artificial intelligence response mechanism for IDS.

Keywords: cyber security, intrusion prevention, optimal policy, Q-learning

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Authors: A. Alyami, S. Christmas, K. Neeltje, G. Pollakis, B. Paxton, Z. Al-Bayati

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The Human leukocyte antigen-G (HLA-G) molecule plays an important role in immunomodulation. To date, 16 untranslated regions (UTR) HLA-G haplotypes have been previously defined by sequenced SNPs in the coding region. From these, UTR-1, UTR-2, UTR-3, UTR-4, UTR-5, UTR-6 and UTR-7 are the most frequent 3’UTR haplotypes at the global level. UTR-1 is associated with higher levels of soluble HLA-G and HLA-G expression, whereas UTR-5 and UTR-7 are linked with low levels of soluble HLA-G and HLA-G expression. Human immunodeficiency virus type 1 (HIV-1) infection results in the progressive loss of immune function in infected individuals. The virus escape mechanism typically includes T lymphocytes and NK cell recognition and lyses by classical HLA-A and B down-regulation, which has been associated with non-classical HLA-G molecule up-regulation, respectively. We evaluated the haplotypes of the HLA-G 3′ untranslated region frequencies observed in three HIV-1 groups from the Netherlands and their susceptibility to develop infection. The three groups are made up of mainly men who have sex with men (MSM), injection drug users (IDU) and a high-risk-seronegative (HRSN) group. DNA samples were amplified with published primers prior sequencing. According to our results, the low expresser frequencies show higher in HRSN compared to other groups. This is indicating that 3’UTR polymorphisms may be identified as potential prognostic biomarkers to determine susceptibility to HIV.

Keywords: Human leukocyte antigen-G (HLA-G) , men who have sex with men (MSM), injection drug users (IDU), high-risk-seronegative (HRSN) group, high-untranslated region (UTR)

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Authors: Anucha Wittayakorn-Puripunpinyoo

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The research objectives were 1) to study the situation and its trend of agricultural product export of Thailand 2) to study the impact of agricultural product export on income of Thai economy 3) the impact of agricultural product export on employment of Thai economy and 4) to find out the recommendations of agricultural product export policy of Thailand. In this research, secondary data were collected as yearly time series data from 1990 to 2016 accounted for 27 years. Data were collected from the Bank of Thailand database. Primary data were collected from the steakholders of agricultural product export policy of Thailand. Data analysis was applied descriptive statistics such as arithmetic mean, standard deviation. The forecasting of agricultural product was applied Mote Carlo Simulation technique as well as time trend analysis. In addition, the impact of agricultural product export on income and employment by applying econometric model while the estimated parameters were utilized the ordinary least square technique. The research results revealed that 1) agricultural product export value of Thailand from 1990 to 2016 was 338,959.5 Million Thai baht with its growth rate of 4.984 percent yearly, in addition, the forecasting of agricultural product export value of Thailand has increased but its growth rate has been declined 2) the impact of agricultural product export has positive impact on income in Thai economy, increasing in agricultural product export of Thailand by 1 percent would lead income increased by 0.0051 percent 3) the impact of agricultural product export has positive impact on employment in Thai economy, increasing in agricultural product export of Thailand by 1 percent would lead income increased by 0.079 percent and 4) in the future, agricultural product export policy would focused on finished or semi-finished agricultural product instead of raw material by applying technology and innovation in to make value added of agricultural product export. The public agricultural product export policy would support exporters in private sector in order to encourage them as agricultural exporters in Thailand.

Keywords: agricultural product export, income, employment, Thai economy

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Authors: Ana Asratashvili

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One of the main issues of state’s economic policy is the environmental problems. The development of society is implementing by the connection with nature. A human being needs different material resources which must be got by the influence on the nature. This relationship between nature and society is complicated and controversial and it was changing from time to time according to human’s evolution. The imprudent and unreasonable usage of natural resources, scientific-technological revolution and the hard pollution of nature related to it caused the disruption of environmental balance between nature and society which has been made for ages and destructively acted on society and environment. Environmental protection is one of the major issues of the European Union all over the world. The aim of EU environmental policy is to improve ecological conditions. Besides, it aims encouraging of careful and rational usage of natural resources. At the same time, the union tries to raise problems related to environmental protection at the international level. After that when scientists concluded anthropogenic impact of human on the nature causes climate changes, the special attention was paid to the environmental protection by developed countries. Global warming will cause floods, storms, draughts and desertification and to solve these results presumably will cost 20% of World GDP by 2050 for developed countries, if, of course, it does not make strict environmental policy. EU member countries have pretty strict environmental standards. Their defense is observed by different state institutions. According to impacts on nature throughout the world the most polluted fumes are made by electricity facilities (44%), transport (20%), industry (18%), domestic and service sector (17%). The special concern to the issues related to the importance of environment by environmentalists is caused by low self-esteem of population about the problems of environment. According to their mind, population is engaged with daily difficulties so that they don’t react much on environmental problems. Correspondingly, the main task for environmental organizations is to inform population and raise self-esteem about environmental issues.

Keywords: economic policy, environment, technological revolution, pollution, environmental, standards, self-esteem

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Authors: E. Batista, R. Mendes, A. Furtado, M. C. Ferreira, I. Godinho, J. A. Sousa, M. Alvares, R. Martins

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Syringe pumps are commonly used for drug delivery in hospitals and clinical environments. These instruments are critical in neonatology and oncology, where any variation in the flow rate and drug dosing quantity can lead to severe incidents and even death of the patient. Therefore it is very important to determine the accuracy and precision of these devices using the suitable calibration methods. The Volume Laboratory of the Portuguese Institute for Quality (LVC/IPQ) uses two different methods to calibrate syringe pumps from 16 nL/min up to 20 mL/min. The Interferometric method uses an interferometer to monitor the distance travelled by a pusher block of the syringe pump in order to determine the flow rate. Therefore, knowing the internal diameter of the syringe with very high precision, the travelled distance, and the time needed for that travelled distance, it was possible to calculate the flow rate of the fluid inside the syringe and its uncertainty. As an alternative to the gravimetric and the interferometric method, a methodology based on the application of optical technology was also developed to measure flow rates. Mainly this method relies on measuring the increase of volume of a drop over time. The objective of this work is to compare the results of the calibration of two syringe pumps using the different methodologies described above. The obtained results were consistent for the three methods used. The uncertainties values were very similar for all the three methods, being higher for the optical drop method due to setup limitations.

Keywords: calibration, flow, interferometry, syringe pump, uncertainty

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Authors: Richard Fairchild, Abdullah Al-Ghazali, Yilmaz Guney

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This study analyses the relationship between managerial overconfidence, dividends, and firm value by developing theoretical models that examine the condition under which managerial overconfident, dividends, and firm value may be positive or negative. Furthermore, the models incorporate moral hazard, in terms of managerial effort shirking, and the potential for the manager to choose negative NPV projects, due to private benefits. Our models demonstrate that overconfidence can lead to higher dividends (when the manager is overconfident about his current ability) or lower dividends (when the manager is overconfident about his future ability). The models also demonstrate that higher overconfidence may result in an increase or a decrease in firm value. Numerical examples are illustrated for both models which interestingly support the models’ propositions.

Keywords: behavioural corporate finance, dividend policy, overconfidence, moral hazard

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Authors: Divya Dawadi, Kerry Bissaker

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Inclusion of children with a disability (CwD) in Early Childhood Education and Development (ECED) programs in Nepal while viewed as desirable is not widespread. Even though the ECED program is currently providing access to ECED services for one million young children, with the aim to improve children's school readiness by equipping them with the necessary knowledge and skills to succeed more effectively in their primary schooling, access to early year's education in inclusive settings for CwD is challenging. Using a heuristic qualitative design, this research aims to construct a framework by analyzing the perspectives of parents and professionals through interviews and focus group discussions, with a view to recommending a new policy to address the rights of CwD and their families. Several school-based and/or organizational and contextual factors interact to contribute to CwD becoming victims of multiple layers of exclusion. The school-based factors include policy, attitudes, teacher efficacy, resources, coordination and parental engagement. The contextual factors are spirituality, caste ethnicity, language, economic status, and geographic location. However, there is a varied effect of the interaction between school-based and contextual factors on different groups of CwD. A policy needs to recognize the multiplicity of the interactions between these factors that inhibit the inclusion of varied groups of CwD in ECED programs and address them separately.

Keywords: children with a disability, early childhood education and development, framework, inclusion

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Authors: R. H. Bustos, L. Martinez, J. García, F. Suárez

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MRP1 (Multi-drug resistance associated protein 1) and MRP2 (Multi-drug resistance associated protein 2) are two proteins belonging to the transporters of ABC (ATP-Binding Cassette). These transporter proteins are involved in the efflux of several biological drugs and xenobiotic and also in multiple physiological, pathological and pharmacological processes. Evidence has been found that there is a correlation among different polymorphisms found and their clinical implication in the resistance to antiepileptic, chemotherapy and anti-infectious drugs. In our study, exonic regions of MRP1/ABCC1 y MRP2/ABCC2 were studied in the Colombian population, specifically in the region of the central Savannah (Cundinamarca) to determinate SNP (Single Nucleotide Polymorphisms) and determinate its allele frequency and its genomics frequency. Results showed that for our population, SNP are found that have been previously reported for MRP1/ABCC1 (rs200647436, rs200624910, rs150214567) as well as for MRP2/ABCC2 (rs2273697, rs3740066, rs142573385, rs17216212). In addition, 13 new SNP were identified. Evidences show an important clinic correlation for polymorphisms rs3740066 and rs2273697. The study object population displays genetic variability as compared to the one reported in other populations.

Keywords: ATP-binding cassette (ABCC), Colombian population, multidrug-resistance protein (MRP), pharmacogenetic, single nucleotide polymorphism (SNP)

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Authors: Wildan Syafitri

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The main purpose of the development is to embody public welfare. Its indication is shown by the increasing of the public prosperity in which it will be related to the consumption level as a consequence of the increasing of public income. One of the government’s efforts to increase public welfare is to create development equity in order to alleviate poor people. Poverty’s problem is not merely about the number and percentage of the poor people, but also it includes the gap and severity of poverty.the analysis method used is Benefit Incidence Analysis (BIA) that is an analysis method used to disclose the impact of government policy or individual access based on the income distribution in society. Further, the finding of the study revealed is that the highest number of the poor people in the village is those who are unemployed and have family members who are still in the Junior High School. The income distribution calculation shows a fairly good budget allocation applied with good mass ratio that is 0.31. In addition, the finding of this study also discloses that Indonesian Government policy to subsidize education cost for Elementary and Junior High School students has reached the right target. It is indicated by more benefits received by Elementary and Junior High School students who are poor and very poor than other income group.

Keywords: benefit incidence analysis, budget allocation, poverty, education

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Authors: Sifen Abreham

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Employees are resources in organizations; as such, they need to be trained and developed properly to achieve an organization's goals and expectations. The initial development of the human resource management concept is based on the effective utilization of people to treat them as resources, leading to the realization of business strategies and organizational objectives. The study aimed to assess the effect of training and development practices on employee performance. The researcher used an explanatory research design, which helps to explain, understand, and predict the relationship between variables. To collect the data from the respondents, the study used probability sampling. From the probability, the researcher used stratified random sampling, which can branch off the entire population into homogenous groups. The result was analyzed and presented by using the statistical package for the social science (SPSS) version 26. The major finding of the study was that the training has an impact on employees' job performance to achieve organizational objectives. The district has a policy and procedure for training and development, but it doesn’t apply actively, and it’s not suitable for district-advised reform this policy and procedure and applied actively; the district gives training for the majority of its employees, but most of the time, the training is theoretical the district advised to use practical training method to see positive change, the district gives evaluation after the employees take training and development, but the result is not encouraging the district advised to assess employees skill gap and feel that gap, the district has a budget, but it’s not adequate the district advised to strengthen its financial ground.

Keywords: training, development, employees, performance, policy

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Authors: Veronika Sharok

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Research relevance on psychological determinants of risky behaviors is caused by high prevalence of such behaviors, particularly among youth. Risky sexual behavior, including unprotected and casual sex, frequent change of sexual partners, drug and alcohol use lead to negative social consequences and contribute to the spread of HIV infection and other sexually transmitted diseases. Data were obtained from 302 respondents aged 15-35 which were divided into 3 empirical groups: persons prone to risky sexual behavior, drug users and alcohol users; and 3 control groups: the individuals who are not prone to risky sexual behavior, persons who do not use drugs and the respondents who do not use alcohol. For processing, we used the following methods: Qualitative method for nominative data (Chi-squared test) and quantitative methods for metric data (student's t-test, Fisher's F-test, Pearson's r correlation test). Statistical processing was performed using Statistica 6.0 software. The study identifies two groups of factors that prevent risky behaviors. Internal factors, which include the moral and value attitudes; significance of existential values: love, life, self-actualization and search for the meaning of life; understanding independence as a responsibility for the freedom and ability to get attached to someone or something up to a point when this relationship starts restricting the freedom and becomes vital; awareness of risky behaviors as dangerous for the person and for others; self-acknowledgement. External factors (prevent risky behaviors in case of absence of the internal ones): absence of risky behaviors among friends and relatives; socio-demographic characteristics (middle class, marital status); awareness about the negative consequences of risky behaviors; inaccessibility to psychoactive substances. These factors are common for proneness to each type of risky behavior, because it usually caused by the same reasons. It should be noted that if prevention of risky behavior is based only on elimination of external factors, it is not as effective as it may be if we pay more attention to internal factors. The results obtained in the study can be used to develop training programs and activities for prevention of risky behaviors, for using values preventing such behaviors and promoting healthy lifestyle.

Keywords: existential values, prevention, psychological features, risky behavior

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Authors: Khaleed Alsufyyan

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This doctoral research has been successfully approved by a specialist upgrade panel, and it presents the proposition that the KSA policy for combating maritime terrorism is inadequate and current governance frameworks, including laws, are insufficiently developed to respond effectively and fairly to maritime terrorism. It will examine the legal system in the KSA in terms of effectiveness fairness, as well as investigate this proposition to determine what factors have contributed to such a deficiency. The main focus of this research will draw upon the policies, laws, and practices of the KSA, as well as UK and international laws and policies, to assess whether it is feasible to apply them in the context of the KSA. This thesis will recommend strategies regarding maritime terrorism to enrich the legal and policy frameworks and address the current and future dynamics of maritime terrorism adequately. To derive suitable improvements, UK policies, laws, and practices will be considered for policy transfer purposes. As for studies focused on the KSA, since the KSA is a Muslim state, it will be important to assess the impact of Islamic Law or Sharia Law subject to the doctrines of fairness and effectiveness to comprehend how the KSA’s legal system operates and determine the boundaries it sets for the response to maritime terrorism. This thesis will propose that more reforms are needed to effectively and fairly deal with maritime terrorism based on the prevailing understanding of Sharia law. The research will address the international perspectives on the problem of maritime terrorism and international cooperation of the KSA regarding maritime terrorism and consider the need for further developments.

Keywords: maritime terrorism, maritime security, combat maritime terrorism in the KSA, protecting maritime transport against terrorism

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Authors: Shivani Yadav

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The paper will first elaborate on the concept of soft power as formulated by Joseph Nye, who argues that soft power is as important as hard power in international politics as it replaces coercion with non-coercive forms of co-optation and attraction. The central tenet of the paper is to extrapolate the continued relevance of soft power in international relations in the 21st century. It is argued that the relevance of soft power, in concurrence with hard power, is on the rise in the international system. This is found to be emanating out of two factors. First, the state-centric practice of international relations has expanded to allow other actors to participate in policymaking. This has led to the resources for power generation to become varied, largely move away from the control of governments, and to produce both hard and soft power attributes. Second, as the currency of coercive power seems to be devaluing in global politics, the role of intangible factors like soft power is getting more important in policymaking. The paper will then go on to elaborate on the critiques of the formulation of soft power from various perspectives, as well as the defenses to these critiques presented by soft power proponents. The paper will reflect on the continued relevance of soft power in international politics by giving the example of India, and how soft power has continued to serve its policy objectives over the years. It is observed that even as India is recognized as a rising superpower today, yet it has made a continuous effort in cultivating its soft power resources, which have proven to be its assets in furthering its foreign policy interests. In conclusion, the paper makes the point that soft power, in conjunction with hard power, will shape international politics in the coming times.

Keywords: foreign policy, India’s soft power, international politics, smart power, soft power

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Authors: Vineeta Sirohi

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The development of critical skills and competencies becomes imperative for young people to cope with the unpredicted challenges of the time and prepare for work and life. Recognizing that education has a critical role in reaching sustainability goals as emphasized by 2030 agenda for sustainability development, educating youth in global competence, meta-cognitive competencies, and skills from the initial stages of formal education are vital. Further, educating for global competence would help in developing work readiness and boost employability. Vocational education and training in India as envisaged in various policy documents remain marginalized in practice as compared to general education. The country is still far away from the national policy goal of tracking 25% of the secondary students at grade eleven and twelve under the vocational stream. In recent years, the importance of skill development has been recognized in the present context of globalization and change in the demographic structure of the Indian population. As a result, it has become a national policy priority and taken up with renewed focus by the government, which has set the target of skilling 500 million people by 2022. This paper provides an overview of the policies, practices, and current status of vocational education and training in India supported by statistics from the National Sample Survey, the official statistics of India. The national policy documents and annual reports of the organizations actively involved in vocational education and training have also been examined to capture relevant data and information. It has also highlighted major initiatives taken by the government to promote skill development. The data indicates that in the age group 15-59 years, only 2.2 percent reported having received formal vocational training, and 8.6 percent have received non-formal vocational training, whereas 88.3 percent did not receive any vocational training. At present, the coverage of vocational education is abysmal as less than 5 percent of the students are covered by the vocational education programme. Besides, launching various schemes to address the mismatch of skills supply and demand, the government through its National Policy on Skill Development and Entrepreneurship 2015 proposes to bring about inclusivity by bridging the gender, social and sectoral divide, ensuring that the skilling needs of socially disadvantaged and marginalized groups are appropriately addressed. It is fundamental that the curriculum is aligned with the demands of the labor market, incorporating more of the entrepreneur skills. Creating nonfarm employment opportunities for educated youth will be a challenge for the country in the near future. Hence, there is a need to formulate specific skill development programs for this sector and also programs for upgrading their skills to enhance their employability. There is a need to promote female participation in work and in non-traditional courses. Moreover, rigorous research and development of a robust information base for skills are required to inform policy decisions on vocational education and training.

Keywords: policy, skill, training, vocational education

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Authors: Enkelejda Koka, Denard Veshi

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Since 2011, in the name of ‘humanitarianism’ and deaths in the Mediterranean Sea, the legal and political justification delivered by Greece to manage the refugee crisis is pre-emptive interception. Although part of the EU, Greece adopted its own strategy. These practices have also created high risks for migrants generally resulting in non-rescue episodes and push-back practices having lethal consequences to the life of the irregular migrant. Thus, this article provides an analysis of the Greek ‘compassionate border work’ policy, a practice known as push-back. It is argued that these push-back practices violate international obligations, notably the ‘right to life’, the ‘duty to search and rescue’, the prohibition of inhuman or degrading treatment or punishment and the principle of non-refoulement.

Keywords: Greece, migrants, push-back policy, violation of international law

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Authors: Emad Heydarnia, Aref Sepasi, Nika Asefi, Sara Khakshournia, Javad Mohammadnejad

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Background: Despite breakthrough therapeutics in breast cancer, it is one of the main causes of mortality among women worldwide. Thus, drug therapies for treating breast cancer have recently been developed by scientists. Metformin and Sorafenib are well-known therapeutic in breast cancer. In the present study, we combined Sorafenib and PCL-sorafenib with metformin to improve drug absorption and promote therapeutic efficiency. Methods: The MCF-7 cells were treated with Metformin, Sorafenib, or PCL-sorafenib. The growth inhibitory effect of these drugs and cell viability were assessed using MTT and flow cytometry assays, respectively. The expression of targeted genes involved in cell proliferation, signaling, and the cell cycle was measured by Real-time PCR. Results: The results showed that MCF-7 cells treated with Metformin/Sorafenib and PCL-sorafenib/Metformin co-treatment contributed to 50% viability compared to untreated group. Moreover, PI and Annexin V staining tests showed that the cells viability for Metformin/Sorafenib and PCL-sorafenib/Metformin was 38% and 17%, respectively. Furthermore, Sorafenib/Metformin and PCL-sorafenib/Metformin leads to p53 gene expression increase by which they can increase ROS, thereby decreasing GPX4 gene expression. In addition, they affected the expression of BCL2, and BAX genes and altered the cell cycle. Conclusion: Together, the combination of PCL-sorafenib/Metformin and Sorafenib/Metformin increased Sorafenib absorption at lower doses and also leads to apoptosis and oxidative stress increases in MCF-7 cells.

Keywords: breast cancer, metformin, nanotechnology, sorafenib

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Authors: Kai-Cheng Hsu, Tzu-Ying Sung, Jinn-Moon Yang

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Colorectal cancer (CRC) is one of the main causes of cancer death in the world. Although several drugs have been developed to treat colorectal cancer, such as Regorafenib and 5-FU, their efficacy is often limited by the development of drug resistance. Therefore, development of new drugs with new scaffolds is necessary to treat CRC. Here, we used site-moiety maps to identify inhibitors against PIM1, LIMK1, SRC, and mTOR, which are often overexpressed in CRC. A site-moiety map represents physicochemical properties and moiety preferences of a binding site through anchors. An anchor contains three elements: (1) conserved interacting residues of a binding pocket; (2) moiety preference of the binding pocket; and (3) the type (e.g., hydrogen-bonding or van der Waals interactions) of interaction between the moieties and the binding pocket. Then, we performed a structure-based virtual screening of ~260,000 compounds and selected compound candidates with high site-moiety map scores for bioassays. Among these candidates, compound 1 and compound 2 inhibited the growth of CRC cells with IC50 values of <10 μM. The experimental result of enzyme-based assays indicated that compound 1 is a dual inhibitor against PIM1 (IC50 6 μM) and LIMK1(IC50 11 μM). Compound 2 was predicted as a SRC inhibitor and will be further validated. The compounds inhibited different protein targets compared to the current drugs. We believe that the compounds provide a starting point to design new drugs for CRC treatment.

Keywords: colorectal cancer, drug discovery, site-moiety map, virtual screening, PIM1, LIMK1

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Authors: Xue Wu

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Since the 1980s, a series of policies and practices have been implemented in China in response to the unprecedented rate of ageing population. The paper provides a detailed narrative of what later-life learning policy discourses have been advocated and gives a description on relevant practical issues during the past three decades. The research process based on the discourse approach with a systematic review of the government-issued documents. It finds that the main practices taken by central government at various levels were making University of the Aged (UA) available in all urban and rural regions to consolidate the newly student enrollments; focusing social-recreational, leisure and cultural activities on 55-75 age group; and utilizing various methods including voluntary works and tourism to improve older adults’ physical and mental wellness. Although there were greater achievements with 30 years of development, many problems still exist. Finding reveals that the curriculum should be modified to meet the needs of the local development, to promote older adults’ contact and contribution to the community, and to enhance technical competences of those in rural areas involving in agricultural production. Central government should also integrate resources from all sectors of the society for further developing later-life learning in China. The result of this paper highlights the value to promote community-based later-life learning for building a society for active ageing and ageing in place.

Keywords: ageing population, China, later-life learning, policy, University of the Aged

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Authors: Mehtab Alam, Mudiarasan Kuppusamy, Puvaneswaran Kunaserkaran

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The purpose of this paper is to bridge the gap and complete the relationship between tourism destinations and image branding as a choice of edifice foreign policy. Such options became a crucial component for individuals interested in leisure and travel activities. The destination management factors have been evaluated and analyzed using the primary and secondary data in a mixed-methods approach (quantitative sample of 384 and qualitative 8 semi-structured interviews at saturated point). The study chose the Environmental Management Accounting (EMA) and Image Restoration (IR) theories, along with a schematic diagram and an analytical framework supported by NVivo software 12, for two locations in Abbottabad, KPK, Pakistan: Shimla Hill and Thandiani. This incorporates the use of PLS-SEM model for assessing validity of data while SPSS for data screening of descriptive statistics. The results show that destination management's promotion of tourism has significantly improved Pakistan's state image. The use of institutional setup, environmental drivers, immigration, security, and hospitality as well as recreational initiatives on destination management is encouraged. The practical ramifications direct the heads of tourism projects, diplomats, directors, and policymakers to complete destination projects before inviting people to Pakistan. The paper provides the extent of knowledge for academic tourism circles to use tourism destinations as brand ambassadors.

Keywords: tourism, management, state image, foreign policy, image branding

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Authors: Siphat Lim

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This study used Autoregressive Distributed Lag (ARDL) approach to cointegration. In the long-run the general price level and exchange rate have a positively significant effect on domestic output. The estimated result further revealed that fiscal stimulus help stimulate domestic output in the long-run, but not in the short-run, while monetary expansion help to stimulate output in both short-run and long-run. The result is complied with the theory which is the macroeconomic policies, fiscal and monetary policy; help to stimulate domestic output in the long-run. The estimated result of the Vector Error Correction Model (VECM) has indicated more clearly that the consumer price index has a positive effect on output with highly statistically significant. Increasing in the general price level would increase the competitiveness among producers than increase in the output. However, the exchange rate also has a positive effect and highly significant on the gross domestic product. The exchange rate depreciation might increase export since the purchasing power of foreigners has increased. More importantly, fiscal stimulus would help stimulate the domestic output in the long-run since the coefficient of government expenditure is positive. In addition, monetary expansion would also help stimulate the output and the result is highly significant. Thus, fiscal stimulus and monetary expansionary would help stimulate the domestic output in the long-run in Cambodia.

Keywords: fiscal policy, monetary policy, ARDL, VECM

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Authors: Sana Ahrar

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Cities are undergoing rapid transformation with the change in lifestyle and technological advancements. These transformations may be experienced or physically visible in the built form. This paper focuses on the relationship between the social, physical environment, change in lifestyle and the interrelated factors influencing the transformation of any historic city. Shahjahanabad as a city has undergone transformation under the various political powers as well as the various policy implementations after independence. These visible traces of transformation diffused throughout the city may be due to socio-economic, historic, political factors and due to the globalization process. This study shall enable evolving a theory for the study of transformation of Historic cities such as Shahjahanabad: which has been plundered, rebuilt, and which still thrives as a ‘living heritage city’. The theory developed will be the process of studying the transformation and can be used by planners, policy makers and researchers in different urban contexts.

Keywords: heritage, historic cities, Shahjahanabad, transformation

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Authors: Ishmael Tingbani

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This paper adopts a contingency theory approach to investigate the relationship between working capital management and profitability using data of 225 listed British firms on the London Stock Exchange for the period 2001-2011. The paper employs a panel data analysis on a series of interactive models to estimate this relationship. The findings of the study confirm the relevance of the contingency theory. Evidence from the study suggests that the impact of working capital management on profitability varies and is constrained by organizational contingencies (environment, resources, and management factors) of the firm. These findings have implications for a more balanced and nuanced view of working capital management policy for policy-makers.

Keywords: working capital management, profitability, contingency theory approach, interactive models

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Authors: Jonathan R. Olsen, Natalie Nicholls, Jenna Panter, Hannah Burnett, Michael Tornow, Richard Mitchell

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The 20-minute neighborhood is a policy priority for governments worldwide and a key feature of this policy is providing access to natural space within 800 meters of home. The study aims were to (1) examine the association between distance to nearest natural space and frequent use over time and (2) examine whether frequent use and changes in use were patterned by income and housing tenure over time. Bi-annual Scottish Household Survey data were obtained for 2013 to 2019 (n:42128 aged 16+). Adults were asked the walking distance to their nearest natural space, the frequency of visits to this space and their housing tenure, as well as age, sex and income. We examined the association between distance from home of nearest natural space, housing tenure, and the likelihood of frequent natural space use (visited once a week or more). Two-way interaction terms were further applied to explore variation in the association between tenure and frequent natural space use over time. We found that 87% of respondents lived within 10 minute walk of a natural space, meeting the policy specification for a 20-minute neighbourhood. Greater proximity to natural space was associated with increased use; individuals living a 6 to 10 minute walk and over 10 minute walk were respectively 53% and 78% less likely to report frequent natural space use than those living within a 5 minute walk. Housing tenure was an important predictor of frequent natural space use; private renters and homeowners were more likely to report frequent natural space use than social renters. Our findings provide evidence that proximity to natural space is a strong predictor of frequent use. Our study provides important evidence that time-based access measures alone do not consider deep-rooted socioeconomic variation in use of Natural space. Policy makers should ensure a nuanced lens is applied to operationalising and monitoring the 20-minute neighbourhood to safeguard against exacerbating existing inequalities.

Keywords: natural space, housing, inequalities, 20-minute neighbourhood, urban design

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Authors: Narjis Zehra

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After automobile revolution 1.0, we have automobile revolution 2.0 standing at the horizon, Autonomous Vehicles (AVs). While the technology is developing into more adaptable form, the conversations around its impact on our cities have already started on multiple scales, from academic institutions and community town halls, to the offices of mayors. In order to explore more the AVs impact on Urban transformation, we first inquire if cities can be redesigned or rebuilt. Secondly, we discuss expectation management for the public and policy in terms of what people think/believe AV technology will deliver, and what the current technological evidence suggests the technology and its adoption will look like. Thirdly, based on these discussions, we take Pittsburgh, PA, as a case study to extrapolate what other cities might need to do in order to prepare themselves for the upcoming technological revolution, that may impact more than just the research institutes. Finally, we conclude by suggesting a political way forward to embed urban design with AV technology for equitable cities of tomorrow.

Keywords: urban design, autonomous vehicles, transformation, policy

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Authors: Riccardo Patriarca, Giulio Di Gravio, Francesco Costantino, Massimo Tronci

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An accurate inventory management policy acquires a crucial role in the several high-availability sectors. In these sectors, due to the high-cost of spares and backorders, an (S-1, S) replenishment policy is necessary for high-availability items. The policy enables the shipment of a substitute efficient item anytime the inventory size decreases by one. This policy can be modelled following the Multi-Echelon Technique for Recoverable Item Control (METRIC). The METRIC is a system-based technique that allows defining the optimum stock level in a multi-echelon network, adopting measures in line with the decision-maker’s perspective. The METRIC defines an availability-cost function with inventory costs and required service levels, using as inputs data about the demand trend, the supplying and maintenance characteristics of the network and the budget/availability constraints. The traditional METRIC relies on the hypothesis that a Poisson distribution well represents the demand distribution in case of items with a low failure rate. However, in this research, we will explore the effects of using a Poisson distribution to model the demand of low failure rate items characterized by an irregular demand trend. This characteristic of a demand is not included in the traditional METRIC formulation leading to the need of revising its traditional formulation. Using the CV (Coefficient of Variation) and ADI (Average inter-Demand Interval) classification, we will define the inherent flaws of Poisson-based METRIC for irregular demand items, defining an innovative ad hoc distribution which can better fit the irregular demands. This distribution will allow defining proper stock levels to reduce stocking and backorder costs due to the high irregularities in the demand trend. A case study in the aviation domain will clarify the benefits of this innovative METRIC approach.

Keywords: METRIC, inventory management, irregular demand, spare parts

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Authors: Nithra Kitreerawutiwong, Sunsanee Mekrungrongwong, Artitaya Wongwonsin, Chakkraphan Phetphoom, Buaploy Phromjang

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Background: Thailand has implemented a district health system based on the concept of primary health care. Since 2014, Family Care Team (FCT) was launched to improve the quality of care through a multidisciplinary team include not only the health sector but also social sector work together. FCT classified into 3 levels: district, sub-district, and community. This system now consists of 66,353 teams, including 3,890 teams at district level, 12,237 teams at the sub-district level, and 50,326 teams at the community level. There is a report regarding assessment the situation and perception on FCT, however, relatively few examined the operationality of this policy. This study aimed to explore the perception of district manager on the process of the implementation of FCT policy and the factors associating to implement FCT in the district health system. Methods/Results: Forty in-depth interviews were performed: 5 of primary care manager at the provincial medical health office, 5 of community hospital director, 5 of district administrative health office, 10 of sub-district health promoting hospital, and 10 of local organization. Semi-structure interview guidelines were used in the discussions. The data was analyzed by thematic analysis. This policy was formulated based on the demographic change and epidemiology transition to serve a long term care for elderly. Facilitator factors are social capital in district health systems such as family health leader and multidisciplinary team. Barrier factors are communication to the frontline provider and local organization. The output of this policy in relation to the structure of FCT is well-defined. Unanticipated effects include training of FCT in community level. Conclusion: Early feedback from healthcare manager is valuable information for the improvement of FCT to function optimally. Moreover, in the long term, health outcome need to be evaluated.

Keywords: family care team, district health system, primary care, qualitative study

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Authors: K. R. Thabethe, G. A. Adefolaju, M. J. Hosie

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Cervical cancer is the third most commonly diagnosed cancer globally and it is one of three AIDS defining malignancies. Highly active antiretroviral therapy (HAART) is a combination of three or more antiretroviral drugs and has been shown to play a significant role in reducing the incidence of some AIDS defining malignancies, although its effect on cervical cancer is still unclear. The aim of this study was to investigate the relationship between cervical cancer and HAART. This was achieved by studying the expression of two signalling molecules expressed in cervical cancer; MUC1 and P65. Following the 24 hour treatment of a cervical cancer cell line, HCS-2, with drugs which are commonly used as part of HAART at their clinical plasma concentrations, real-time qPCR and immunofluorescence were used in order to study gene and protein expression. A one way ANOVA followed by a Tukey Kramer Post Hoc test was conducted using JMP 11 software on both sets of data. The drug classified as a protease inhibitor (PI) (i.e. LPV/r) reduced MUC1 and P65 gene and protein expression more than the other drug tested. PIs are known to play a significant role in cell death, therefore the cells were thought to be more susceptible to cell death following treatment with PIs. In conclusion, the drugs used, especially the PI showed some anticancer effects by facilitating cell death through decreased gene and protein expression of MUC1 and P65 and present promising agents for cancer treatment.

Keywords: cervical cancer, haart, MUC1, P65

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Authors: Vichayada Laohapiboolkul

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Introduction: As the legal use of cannabis is being widely accepted throughout the world, medical cannabis has been explored in order to become an alternative cure for patients. Tetrahydrocannabinol (THC) and Cannabidiol (CBD) are natural cannabinoids found in the Cannabis plant which is proved to have positive treatment for various diseases and symptoms such as chronic pain, neuropathic pain, spasticity resulting from multiple sclerosis, reduce cancer-associated pain, autism spectrum disorders (ASD), dementia, cannabis and opioid dependence, psychoses/schizophrenia, general social anxiety, posttraumatic stress disorder, anorexia nervosa, attention-deficit hyperactivity disorder, and Tourette's disorder. Regardless of all the medical benefits, THC, if not metabolized, can lead to mild up to severe adverse drug reactions (ADR). The enzyme CYP2C19 was found to be one of the metabolizers of THC. However, the suballele CYP2C19*2 manifests as a poor metabolizer which could lead to higher levels of THC than usual, possibly leading to various ADRs. Objective: The aim of this study was to investigate the distribution of CYP2C19, specifically CYP2C19*2, genes in Thai patients treated with medical cannabis along with adverse drug reactions. Materials and Methods: Clinical data and EDTA whole blood for DNA extraction and genotyping were collected from patients for this study. CYP2C19*2 (681G>A, rs4244285) genotyping was conducted using the Real-time PCR (ABI, Foster City, CA, USA). Results: There were 42 medical cannabis-induced ADRs cases and 18 medical cannabis tolerance controls who were included in this study. A total of 60 patients were observed where 38 (63.3%) patients were female and 22 (36.7%) were male, with a range of age approximately 19 - 87 years. The most apparent ADRs for medical cannabis treatment were dry mouth/dry throat (76.7%), followed by tachycardia (70%), nausea (30%) and a few arrhythmias (10%). In the total of 27 cases, we found a frequency of 18 CYP2C19*1/*1 alleles (normal metabolizers, 66.7%), 8 CYP2C19*1/*2 alleles (intermediate metabolizers, 29.6%) and 1 CYP2C19*2/*2 alleles (poor metabolizers, 3.7%). Meanwhile, 63.6% of CYP2C19*1/*1, 36.3% and 0% of CYP2C19*1/*2 and *2/*2 in the tolerance controls group, respectively. Conclusions: This is the first study to confirm the distribution of CYP2C19*2 allele and the prevalence of poor metabolizer genes in Thai patients who received medical cannabis for treatment. Thus, CYP2C19 allele might serve as a pharmacogenetics marker for screening before initiating treatment.

Keywords: medical cannabis, adverse drug reactions, CYP2C19, tetrahydrocannabinol, poor metabolizer

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Authors: Rika van Zyl

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South Africa’s racial discrimination past has led to the drafting of the Constitution with the Bill of Rights for the people of South Africa. The Bill of Rights prohibits the state from unfairly discriminating directly or indirectly on certain grounds, one of which is race and another is gender. This has forced changes to the law of succession. The customary law rule of male primogeniture was abolished to ensure that women were not excluded from the intestate succession of the male head of the family in 2005. It was said that this rule cannot be reconciled with the notions of equality and human dignity contained in the Bill of Rights. The freedom of testation has further come under fire in South Africa, where it was found to be unfair discrimination and against public policy to exclude a specific gender (women) from inheriting in a private will. Although no one has the right to inherit in South Africa, any person with an interest can approach the court alleging that a right in the Bill of Rights has been infringed. A will that is found inconsistent with the South African Bill of Rights then cannot be enforced. Recent case law found that to leave out a specific gender (women) from a will, based entirely on the fact that they are of said specific gender, is in contravention of the Constitution and should, therefore, be declared invalid. It was said that the courts should take a transformative constitutional approach when equality rights are affected. Otherwise, the historical and insidious unequal distribution of wealth in South Africa will continue along the fault lines such as gender. This decision has opened the debate on the extent to which the state can interfere with the private autonomy of an individual who is deceased. Some of these arguments will be discussed, including the ambit of public policy in this regard.

Keywords: equality, discrimination, succession, public policy

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