Search results for: drug policy

Authors: Prakash Chittoor

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In the recent past, it is realised especially in third sector that employing social innovation is crucial for achieving viable and long lasting social transformation. In this context, education is one among many sectors that have opened up itself for such move where employing social innovation emerges as key for reaching out to the excluded sections who are often failed to get support from either policy or market interventions. In fact, education is being as a crucial factor for social development is well understood at both academic and policy level. In order to move forward to achieve better results, interventions from multiple sectors may be required as its reach cultivates capabilities and skill of the deprived in order to ensure both market and social participation in the long run. Despite state’s intervention, it is found that still millions of children are out of school due to lack of political will, lapses in policy implementation and neoliberal intervention of marketization. As a result, universalisation of elementary education became as an elusive goal to poor and marginalised sections where state obtain constant pressure by corporate sector to withdraw from education sector that led convince in providing quality education. At this juncture, the role of third sector organizations plays is quite remarkable. Especially, it has evolved as a key player in education sector to reach out to the poor and marginalised in the far-flung areas. These organisations work in resources constrain environment, yet, in order to achieve larger social impact they adopt various social innovations from time to time to reach out to the unreached. Their attempts not only limited to just approaching the unreached children but to retain them for long-time in the schooling system in order to ripe the results for their families and communities. There is a need to highlight various innovative ways adopted and practiced by the third sector organisations in India to achieve the elusive goal of universal access of primary education with quality. With this background, the paper primarily attempts to present an in-depth understanding about innovative practices employed by third sectors organisations like Isha Vidya through government schools adoption programme in India where it engages itself with government and build capabilities among the government teachers to promote state run schooling with quality and better infrastructure. Further, this paper assess whether such innovative attempts succeeded in to achieving universal quality education in the areas where it operates and draws implications for State policy.

Keywords: school education, third sector organisations, social innovation, market domination

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Authors: Sajjad Farahani, Wilkistar Otieno, Xiaohang Yue

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This paper develops a model for the optimal disposition decision for product returns in a remanufacturing system with limited recoverable inventory capacity. In this model, a constant demand is satisfied by remanufacturing returned products which are up to the minimum required quality grade. The quality grade of returned products is uncertain and remanufacturing cost increases as the quality level decreases, and remanufacturer wishes to determine which returned product to accept to be remanufactured for reselling, and any unaccepted returns may be salvaged at a value that increases with their quality level. Accepted returns can be stocked for remanufacturing upon demand requests, but incur a holding cost. A Markov decision problem is formulated in order to evaluate various performance measures for this system and obtain the optimal remanufacturing policy. A detailed numerical study reveals that our approach to the disposition problem outperforms the current industrial practice ignoring quality grade of returned products. In addition, we identify conditions under which this improvement is the highest.

Keywords: green supply chain management, matrix geometric method, production recovery, reverse supply chains

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Authors: Sapfo A. Mortaki

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From the early 1960s and until the middle of the next decade, the lack of favorable conditions for the development of art along with the imposition of the 1967 military dictatorship resulted in a great flow of Greek artists abroad. The fall of the dictatorship and the change of the political scene after 1974 constitute crucial milestones in the cultural life of the country. In the field of visual arts significant changes are attempted in the state's effort to formulate a national cultural policy. This article examines the presence of Greek migrant artists (painters and sculptors) in Paris during the 1970s. Since the mid-1970s, and particularly in the early 1980s, Modern Greek Diaspora undergoes a new transition phase, when the concept of immigration changes. The aim of this study is to record and give prominence to the presence of the Greek artists -through archival research in the daily and periodical press- as well as present the impact of their artistic activity on French intellectual life and on the country’s society during this period. Furthermore, the presence and work of these artists are discussed in an environment of cultural coexistence which, to a certain extent, can be regarded as the result of the social phenomenon of their migration in the era of postmodernity. Finally, their contribution to the development of the cultural life of Greece, inside and outside its borders, is also being examined.

Keywords: art and society, cultural policy, Greek artists, postmodernity

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Authors: Mohamed A. Hammad, Dzul Azri Mohamed Noor, Syed Azhar Syed Sulaiman, Abeer Kharshid, Nor Azizah Aziz, Tarek M. Elsayed

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Medication safety is always an issue. In 2015, the National Pharmaceutical Control Bureau released a statement requesting all statins manufacturers in Malaysia to include the risk of diabetes information in the drug information leaflet in response to United States Food and Drug Administration (U.S. FDA) report. However, the data regarding this warning label in Malaysia is limited, so there is still some uncertainty whether such risk can also be observed in the Malaysian population or not. The study aims to determine the effect of statins on HbA1c% in type 2 diabetic outpatients in endocrine clinics at Hospital Pulau Pinang between June 2015 and May 2016 in Malaysia. In a prospective cohort study, records of 400 type 2 diabetic patients (control group 104 patients not using statin and treatment group 296 patients using statin) were reviewed to identify demographic criteria and lab tests. The prevalence of glycemic control (Glycated hemoglobin, HbA1C ≤ 7% for patient < 65 years, and < 8% for patient ≥ 65 years) was estimated, according to American Diabetes Association guidelines 2015. The results were presented as descriptive statistics. From 296 patients with Type 2 diabetes using statins cohort with a mean age of 57.52 ± 12.2 years, only 81 (27.4%) cases had controlled glycemia, and 215 (72.6%) had uncontrolled glycemia, CI: 95% (6.3–11.1). While the control group 104 diabetic patients had a mean age 46.1 ± 18 years and distributed among 59 (56.7%) patients with controlled diabetes and 45 (43.3%) cases, had uncontrolled glycemia, CI: 95% (5.2–10.3). The relative risk (RR) of uncontrolled glycemia in diabetic patients used statins was 1.68, and the excessive relative risk (ERR) was 68%. The absolute risk (AR) was 29.3%, and the number needed to harm (NNH) was 4. Diabetic patients using statins have more risk of uncontrolled glycemia than the patients with Type 2 diabetes non-using statins.

Keywords: diabetes mellitus, HbA1c, Malaysia, outpatients, statin, type 2, uncontrolled glycemia

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Authors: Mahboubeh Kabiri, Saba Aslani

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Among various approaches used for the treatment of cardiovascular diseases, the occlusion of the small-diameter vascular graft (SDVG) is still an unresolved problem which seeks further research to address them. Though autografts are now the gold standards to be replaced for blocked coronary arteries, they suffer from inadequate quality and quantity. On the other hand, the major problems of the tissue engineered grafts are thrombosis and intimal hyperplasia. Provision of a suitable spatiotemporal release pattern of anticoagulant agents such as heparin and aspirin can be a step forward to overcome such issues . Herein, we fabricated electrospun scaffolds from FDA (Food and Drug Administration) approved poly-L-lactic acid (PLLA) with aspirin loaded into the nanofibers. Also, we surface coated the scaffolds with Amniotic Membrane lysate as a source for natural elastic polymers and a mimic of endothelial basement membrane. The scaffolds were characterized thoroughly structurally and mechanically for their morphology, fiber orientation, tensile strength, hydrophilicity, cytotoxicity, aspirin release and cell attachment support. According to the scanning electron microscopy (SEM) images, the size of fibers ranged from 250 to 500 nm. The scaffolds showed appropriate tensile strength expected for vascular grafts. Cellular attachment, growth, and infiltration were proved using SEM and MTT (3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide) assay. Drug-loaded scaffolds showed a sustained release profile of aspirin in 7 days. An enhanced cytocompatibility was observed in AM-coated electrospun PLLA fibers compared to uncoated scaffolds. Our results together indicated that AM lysate coated ASA releasing scaffolds have promising potentials for development of a biocompatible SDVG.

Keywords: vascular tissue engineering, vascular grafts, anticoagulant agent, aspirin, amniotic membrane

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Authors: Kiran Bala

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Health, education and employment opportunities available for a common citizen reflect the development status of a country. Health of an individual affects the growth of a country in every aspect. According to a study by WHO, India is estimated to lose more than $237 billion of its GDP over the period 2006-15 on account of premature death and morbidity from Non-communicable diseases alone. Each year 37 million people fall below poverty line due to high expenditure on health services they have to incur. Falling sick puts a double burden on them in terms of loss of income and expenditure on health care which pushes them further into debt and poverty. Adding to the gravity of situation, public spending on health in India has itself declined after liberalization from 1.3% of GDP in 1990 to 0.9% in 1999. The Approach Paper of the Government of India to the Twelfth Five Year Plan indicated that health expenditure alone as a per cent of GDP was about 1.4 per cent (B.E.) in 2011-12. It also mentioned that if one included expenditure on rural water supply and sanitation, the figure would be about 1.8 per cent. Given the abysmally low level of priority accorded to health in Indian economic policy, it becomes rather important to study the representation of health in the Indian public sphere. To this end, this study examines the prioritization of health in the public policy agenda of the national/regional political parties as evidenced in their election manifestos at a time when the nation is poised to go for the General Elections. The paper also focuses attention on the prioritization of health in the public perception as evidenced in their reasons for their preferences for a particular party or individual contestant. To arrive at the reasons for the priority level accorded by the political actors and the citizens, the study uses Focus groups of health policy makers, media persons, medical practitioners and voters. Collected data will be analysed in the theoretical framework of spiral of silence and agenda setting theory.

Keywords: health, election manifestos, public perception, policies

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Authors: Narin Ozturk, Xiao-Mei Li, Sylvie Giachetti, Francis Levi, Alper Okyar

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P-glycoprotein (P-gp, MDR1, ABCB1) is a transmembrane protein acting as an ATP-dependent efflux pump and functions as a biological barrier by extruding drugs and xenobiotics out of cells in healthy tissues especially in intestines, liver and brain as well as in tumor cells. The circadian timing system controls a variety of biological functions in mammals including xenobiotic metabolism and detoxification, proliferation and cell cycle events, and may affect pharmacokinetics, toxicity and efficacy of drugs. Selective mTOR (mammalian target of rapamycin) inhibitor everolimus is an immunosuppressant and anticancer drug that is active against many cancers, and its pharmacokinetics depend on P-gp. The aim of this study was to investigate the dosing time-dependent toxicity of everolimus with respect to the intestinal P-gp expression rhythms in mdr1a::Luc mice using Real Time-Biolumicorder (RT-BIO) System. Mdr1a::Luc male mice were synchronized with 12 h of Light and 12 h of Dark (LD12:12, with Zeitgeber Time 0 – ZT0 – corresponding Light onset). After 1-week baseline recordings, everolimus (5 mg/kg/day x 14 days) was administered orally at ZT1-resting period- and ZT13-activity period- to mdr1a::Luc mice singly housed in an innovative monitoring device, Real Time-Biolumicorder units which let us monitor real-time and long-term gene expression in freely moving mice. D-luciferin (1.5 mg/mL) was dissolved in drinking water. Mouse intestinal mdr1a::Luc oscillation profile reflecting P-gp gene expression and locomotor activity pattern were recorded every minute with the photomultiplier tube and infrared sensor respectively. General behavior and clinical signs were monitored, and body weight was measured every day as an index of toxicity. Drug-induced body weight change was expressed relative to body weight on the initial treatment day. Statistical significance of differences between groups was validated with ANOVA. Circadian rhythms were validated with Cosinor Analysis. Everolimus toxicity changed as a function of drug timing, which was least following dosing at ZT13, near the onset of the activity span in male mice. Mean body weight loss was nearly twice as large in mice treated with 5 mg/kg everolimus at ZT1 as compared to ZT13 (8.9% vs. 5.4%; ANOVA, p < 0.001). Based on the body weight loss and clinical signs upon everolimus treatment, tolerability for the drug was best following dosing at ZT13. Both rest-activity and mdr1a::Luc expression displayed stable 24-h periodic rhythms before everolimus and in both vehicle-treated controls. Real-time bioluminescence pattern of mdr1a revealed a circadian rhythm with a 24-h period with an acrophase at ZT16 (Cosinor, p < 0.001). Mdr1a expression remained rhythmic in everolimus-treated mice, whereas down-regulation was observed in P-gp expression in 2 of 4 mice. The study identified the circadian pattern of intestinal P-gp expression with an unprecedented precision. The circadian timing depending on the P-gp expression rhythms may play a crucial role in the tolerability/toxicity of everolimus. The circadian changes in mdr1a genes deserve further studies regarding their relevance for in vitro and in vivo chronotolerance of mdr1a-transported anticancer drugs. Chronotherapy with P-gp-effluxed anticancer drugs could then be applied according to their rhythmic patterns in host and tumor to jointly maximize treatment efficacy and minimize toxicity.

Keywords: circadian rhythm, chronotoxicity, everolimus, mdr1a::Luc mice, p-glycoprotein

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Authors: Edith Kamakune

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As much as Indigenous rights are presumed to be part of the broad human rights regime, members of the indigenous communities have continually suffered violations, exclusions, and threat. There are a number of steps taken from the international community in trying to bridge the gap, and this has been through the inclusion of provisions as well as the passing of conventions and declarations with specific reference to the rights of indigenous peoples. Some examples of indigenous people include theSiberian Yupik of St Lawrence Island; the Ute of Utah; the Cree of Alberta, and the Xosa andKhoiKhoi of Southern Africa. Uganda’s wide cultural heritage has played a key role in the failure to pay special attention to the needs of the rights of indigenous peoples. The 1995 Constitution and the Land Act of 1998 provide for abstract land rights without necessarily paying attention to indigenous communities’ special needs. Basongora are a pastoralist community in Western Uganda whose ancestral land is the present Queen Elizabeth National Park of Western Uganda, Virunga National Park of Eastern Democratic Republic of Congo, and the small percentage of the low lands under the Rwenzori Mountains. Their values and livelihood are embedded in their strong attachment to the land, and this has been at stake for the last about 90 Years. This research was aimed atinvestigating the relationship between land rights and the right to cultural identity among indigenous communities, looking at the policy available on land and culture, and whether the policies are sensitive of the specific issues of vulnerable ethnic groups; and largely the effect of land on the right to cultural identity. The research was guided by three objectives: to examine and contextualize the concept of land rights among the Basongora community; to assess the policy frame work available for the protection of the Basongora community; to investigate the forms of vulnerability of the Basongora community. Quantitative and qualitative methods were used. a case of Kaseseand Kampala Districts were purposefully selected .138 people were recruited through random and nonrandom techniques to participate in the study, and these were 70 questionnaire respondents; 20 face to face interviews respondents; 5 key informants, and 43 participants in focus group discussions; The study established that Land is communally held and used and thatit continues to be a central source of livelihood for the Basongora; land rights are important in multiplication of herds; preservation, development, and promotion of culture and language. Research found gaps in the policy framework since the policies are concerned with tenure issues and the general provisions areambiguous. Oftenly, the Basongora are not called upon to participate in decision making processes, even on issues that affect them. The research findings call forauthorities to allow Basongora to access Queen Elizabeth National Park land for pasture during particular seasons of the year, especially during the dry seasons; land use policy; need for a clear alignment of the description of indigenous communitiesunder the constitution (Uganda, 1995) to the international definition.

Keywords: cultural identity, land rights, protection, uganda

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Authors: Ana Cristina A. P. Carvalho, Solange Teles Da Silva

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In April, 174 countries signed the Paris Agreement, a multilateral agreement on climate change which deals with greenhouse gas emissions, mitigation, adaptation, finance, access to information, transparency, among other subjects related to the environment. Since then, Parties shall cooperate in taking measures, as appropriate, to enhance climate change education, training, public awareness, public participation and public access to information, recognizing the importance of these steps with respect to enhancing actions under this Agreement. This paper aims to analyze the consequences of this new rule in terms of the implementation of the Agreement, collecting data from Brazilian and Canadian legislations in order to identify if these countries have rules complying with the Treaty, the steps that have been already taken and if they could be used as examples for other countries. The analysis will take into consideration the different kinds of climate change information, means of transparency, reliability of the data and how to spread the information. The methodology comprehends a comparative legal research based on both the Paris Agreement and domestic laws of Brazil and Canada, as well as on doctrine and Court decisions. The findings can contribute to the implementation of the Paris Agreement through compliance with this Treaty at countries’ domestic and policy level.

Keywords: climate change information, domestic legislation, Paris Agreement, public policy

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Authors: Ramon F. B. da Silva, Mateus Batistella, Emilio Moran

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Although the existence of two Forest Transition (FT) pathways, the economic development and the forest scarcity, there are many contexts that shape the model of FT observed in each particular region. This means that local conditions, such as relief, soil quality, historic land use/cover, public policies, the engagement of society in compliance with legal regulations, and the action of enforcement agencies, represent dimensions which combined, creates contexts that enable forest regeneration. From this perspective we can understand the regeneration process of native vegetation cover in the Paraíba Valley (Forest Atlantic biome), ongoing since the 1960s. This research analyzed public information, land use/cover maps, environmental public policies, and interviewed 17 stakeholders from the Federal and State agencies, municipal environmental and agricultural departments, civil society, farmers, aiming comprehend the contexts behind the forest regeneration in the Paraíba Valley, Sao Paulo State, Brazil. The first policy to protect forest vegetation was the Forest Code n0 4771 of 1965, but this legislation did not promote the increase of forest, just the control of deforestation, not enough to the Atlantic Forest biome that reached its highest pick of degradation in 1985 (8% of Atlantic Forest remnants). We concluded that the Brazilian environmental legislation acted in a strategic way to promote the increase of forest cover (102% of regeneration between 1985 and 2011) from 1993 when the Federal Decree n0 750 declared the initial and advanced stages of secondary succession protected against any kind of exploitation or degradation ensuring the forest regeneration process. The strategic policy formulation was also observed in the Sao Paulo State law n0 6171 of 1988 that prohibited the use of fire to manage agricultural landscape, triggering a process of forest regeneration in formerly pasture areas.

Keywords: forest transition, land abandonment, law enforcement, rural economic crisis

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Authors: Naylya Djumaeva

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Since the end of 2019, the world has been shaken by an infection that has claimed the lives of more than six and a half million patients. Currently, SARS-CoV-2 not only causes acute damage but has long-term consequences affecting every organ and has brought a wave of a new chronic disabling condition called Long-Covid..This preliminary study describes an application of un-explored properties of low-level laser radiation with laser- light emitter in the field of which is placed Copegus (Ribavirin) with the aim of treatment of patients with Long-Covid syndrome. The difference from the traditional use of the drug is that Copegus was not prescribed to the patient by the traditional method - orally or intravenously, and the medicinal properties of the drug were introduced into the patient’s body using the un-explored properties of low-power laser radiation. Ninety eight patients with Long- Covid syndrome were observed. The obtained findings suggest that under the influence of the field formed into the laser- light emitter with a Copegus placed inside the field, the remote transfer of pharmacological properties of Сopegus occurs. Conclusions about the produced effect of exposure were made based on improvement in the condition of patients, the disappearance of complaints, and positive changes in various diagnostic tests performed by the patients. Biography: Djumaeva N completed her PhD from the Institute of Epidemiology, Microbiology and Infectious Diseases in 2000. In her dissertation work devoted to the treatment of patients with chronic hepatitis B virus infection, she presented data on the possible influence of Complex Homeopathic Preparations on the organization of bound intracellular water in the cells of the body. She is the Consultant (Neurologist) at the Scientific-Research Institute for Virology, Uzbekistan, and an expert in “medicament testing” method (30 years). She has published 43 papers, including 2 patents.

Keywords: long covid, low level laser, copegus, laser- light emmiter

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Authors: Chineduum Okpala

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Nigeria, since her independence, has been engulfed in financial crimes of different forms. From embezzlement and conversion of public funds by public servants to stealing, contract inflation, and money laundering. Money laundering in Nigeria, particularly by political exposed persons, has been an issue of concern since independence. Corruption has been endemic, and Nigeria needs to integrate pro-active measures to show to the international community that it is ready to move against this vice. This paper discusses the negative effect of corruption and its effect on prosecutorial discretion. It also takes cognisance of the policy and aims of the anti-money laundering (AML) policy as enacted in Nigeria. It also takes as valid the assumption that the effective application of the rule of law will improve the efficacy of the Nigerian regime. In this regard, the perspective is internal to the Nigerian regime and its internal policy discourse which also reflect its policy discourse at international level. This paper takes notice of the typology of money laundering (ML) offences that most affect Nigeria, which hinges on corruption and abuse of office by a specific type of person, politically exposed persons (PEP). This typology of money laundering offence appears to be the most prevalent in developing nations like Nigeria. The application of essential principles of law provides an opportunity for the internalisation of the rule of law in the anti-money laundering regime in Nigeria, which could aid the successful prosecution of politically exposed persons on money laundering offences. The rule of law and how well the Nigerian legal system manages to deal with the interface between high level politics and the criminal justice system in Nigeria cannot be understood from internal sources but must be developed as a genuine but critical account informed by perspectives external to the Nigerian regime. If the efficacy of the regime is to be assessed in view of notorious failures of the regime, an external assessment is needed. Hence the paper discusses the need to integrate the essential principles of law in the application of prosecutorial discretion in the anti-money laundering regime in Nigeria, particularly with politically exposed persons. The paper highlights jurisdiction where prosecutorial discretion is integrated into the anti-money laundering regime in accordance to the rule of law which forms a basis for comparative analysis of the success of the anti-money laundering regime in Nigeria. This paper discusses why the application of prosecutorial discretion should not be used as a tool to extricate or avail the rich and powerful in the society from justice. The paper aims to argue that the successful prosecution of politically exposed persons, will raise the confidence of the citizens and the international community in the anti-money laundering regime in Nigeria.

Keywords: money laundering, politically exposed persons, corruption, Nigeria

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Authors: Pawan Kumar Gupta, Sumana Ghosh

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Parkinson's Disease (PD) is a long-term neurodegenerative movement disorder of the central nervous system with vast symptoms related to the motor system. The common symptoms of PD are tremor, rigidity, bradykinesia/akinesia, and postural instability, but the clinical symptom includes other motor and non‐motor issues. The motor symptoms of the disease are consequence of death of the neurons in a region of the midbrain known as substantia nigra pars compacta, leading to decreased level of a neurotransmitter known as dopamine. The cause of this neuron death is not clearly known but involves formation of Lewy bodies, an abnormal aggregation or clumping of the protein alpha-synuclein in the neurons. Unfortunately, there is no cure for PD, and the management of this disease is challenging. Therefore, it is critical for a patient to be diagnosed at early stages. A limited choice of drugs is available to improve the symptoms, but those become less and less effective over time. Apart from that, with rapid growth in the field of science and technology, other methods such as multi-area brain stimulation are used to treat patients. In order to develop advanced techniques and to support drug development for treating PD patients, an accurate mathematical model is needed to explain the underlying relationship of dopamine secretion in the brain with the hand tremors. There has been a lot of effort in the past few decades on modeling PD tremors and treatment effects from a computational point of view. These models can effectively save time as well as the cost of drug development for the pharmaceutical industry and be helpful for selecting appropriate treatment mechanisms among all possible options. In this review paper, an effort is made to investigate studies on PD modeling and analysis and to highlight some of the key advances in the field over the past centuries with discussion on the current challenges.

Keywords: Parkinson's disease, deep brain stimulation, tremor, modeling

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Authors: Asiya Mahtab, Sushama Talegaonkar

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The research is aimed at developing targeted lipid-based nanocarrier systems of chondroitin sulfate (CS) to deliver an antirheumatic drug to the inflammatory site in arthritic paw. Lipid-based nanoparticle (TEF-lipo) was prepared by using a thin-film hydration method. The coating of prepared drug-loaded nanoparticles was done by the ionic interaction mechanism. TEF-lipo and CS-coated lipid nanoparticle (CS-lipo) were characterized for mean droplet size, zeta potential, and surface morphology. TEF-lipo and CS-lipo were further subjected to in vitro cell line studies on RAW 264.7 murine macrophage, U937, and MG 63 cell lines. The pharmacodynamic study was performed to establish the effectiveness of the prepared lipid-based conventional and targeted nanoparticles in comparison to pure drugs. Droplet size and zeta potential of TEF-lipo were found to be 128. 92 ± 5.42 nm and +12.6 ± 1.2 mV. It was observed that after the coating of TEF-lipo with CS, particle size increased to 155.6± 2.12 nm and zeta potential changed to -10.2± 1.4mV. Transmission electron microscopic analysis revealed that the nanovesicles were uniformly dispersed and detached from each other. Formulations followed sustained release pattern up to 24 h. Results of cell line studies ind icated that CS-lipo formulation showed the highest cytotoxic potential, thereby proving its enhanced ability to kill the RAW 264.7 murine macrophage and U937 cells when compared with other formulations. It is clear from our in vivo pharmacodynamic results that targeted nanocarriers had a higher inhibitory effect on arthritis progression than nontargeted nanocarriers or free drugs. Results demonstrate that this approach will provide effective treatment for rheumatoid arthritis, and CS served as a potential prophylactic against the advancement of cartilage degeneration.

Keywords: adjuvant induced arthritis, chondroitin sulfate, rheumatoid arthritis, teriflunomide

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Authors: Sidra Shaw, Sarenna Shaw, Chae Joon Lee, Irimpan Mathews, Eric Koehn

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One of the biggest public health concerns of our time is increasing antimicrobial resistance. As of 2019, the CDC has documented more than 2.8 million serious antibiotic resistant infections in the United States. Currently, antibiotic resistant infections are directly implicated in over 750,000 deaths per year globally. On our current trajectory, British economist Jim O’Neill predicts that by 2050, an additional 10 million people (about half the population of New York) will die annually due to drug resistant infections. As a result, new biochemical pathways must be targeted to generate next generation antibiotic drugs that will be effective against drug resistant bacteria. One enticing target is the biosynthesis of DNA within bacteria, as few drugs interrupt this essential life process. Thymidylate synthase enzymes are essential for life as they catalyze the synthesis of a DNA building block, 2′-deoxythymidine-5′-monophosphate (dTMP). In humans, the thymidylate synthase enzyme (TSase) has been shown to be distinct from the flavin-dependent thymidylate synthase (FDTS) produced by many pathogenic bacteria. TSase and FDTS have distinct structures and mechanisms of catalysis, which should allow selective inhibition of FDTS over human TSase. Currently, C. diff is one of the most antibiotic resistant bacteria, and no drugs that target thymine biosynthesis exist for C. diff. Here we present the initial biochemical characterization of FDTS from C. diff. Specifically, we examine enzyme kinetics and binding features of this enzyme to determine the nature of interaction with ligands/inhibitors and understand the molecular mechanism of catalysis. This research will provide more insight into the targetability of the C. diff FDTS enzyme for novel antibiotic drugs.

Keywords: flavin-dependent thymidylate synthase, FDTS, clostridioides difficile, C. diff, antibiotic resistance, DNA synthesis, enzyme kinetics, binding features

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Authors: Murali Aarthy, Sanjeev Kumar Singh

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High risk human papillomaviruses are highly associated with the carcinoma of the cervix and the other genital tumors. Cervical cancer develops through the multistep process in which increasingly severe premalignant dysplastic lesions called cervical intraepithelial neoplastic progress to invasive cancer. The oncoprotein E7 of human papillomavirus expressed in the lower epithelial layers drives the cells into S-phase creating an environment conducive for viral genome replication and cell proliferation. The replication of the virus occurs in the terminally differentiating epithelium and requires the activation of cellular DNA replication proteins. To date, no suitable drug molecule is available to treat HPV infection whereas identification of potential drug targets and development of novel anti-HPV chemotherapies with unique mode of actions are expected. Hence, our present study aimed to identify the potential inhibitors analogous to EGCG, a green tea molecule which is considered to be safe to use for mammalian systems. A 3D similarity search on the natural small molecule library from natural product database using EGCG identified 11 potential hits based on their similarity score. The structure based docking strategies were implemented in the potential hits and the key interacting residues of protein with compounds were identified through simulation studies and binding free energy calculations. The conformational changes between the apoprotein and the complex were analyzed with the simulation and the results demonstrated that the dynamical and structural effects observed in the protein were induced by the compounds and indicated the dominance to the oncoprotein. Overall, our study provides the basis for the structural insights of the identified potential hits and EGCG and hence, the analogous compounds identified can be potent inhibitors against the HPV 16 E7 oncoprotein.

Keywords: EGCG, oncoprotein, molecular dynamics simulation, analogues

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Authors: Nigar Kantarci Carsibasi

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Coarse-grained elastic network models, namely Gaussian network model (GNM) and Anisotropic network model (ANM), are utilized in order to investigate the fluctuation dynamics of Murine Double Minute 2 (MDM2), which is the native inhibitor of p53. Conformational dynamics of MDM2 are elucidated in unbound, p53 bound, and non-peptide small molecule inhibitor bound forms. With this, it is aimed to gain insights about the alterations brought to global dynamics of MDM2 by native peptide inhibitor p53, and two small molecule inhibitors (HDM201 and NVP-CGM097) that are undergoing clinical stages in cancer studies. MDM2 undergoes significant conformational changes upon inhibitor binding, carrying pieces of evidence of induced-fit mechanism. Small molecule inhibitors examined in this work exhibit similar fluctuation dynamics and characteristic mode shapes with p53 when complexed with MDM2, which would shed light on the design of novel small molecule inhibitors for cancer therapy. The results showed that residues Phe 19, Trp 23, Leu 26 reside in the minima of slowest modes of p53, pointing to the accepted three-finger binding model. Pro 27 displays the most significant hinge present in p53 and comes out to be another functionally important residue. Three distinct regions are identified in MDM2, for which significant conformational changes are observed upon binding. Regions I (residues 50-77) and III (residues 90-105) correspond to the binding interface of MDM2, including (α2, L2, and α4), which are stabilized during complex formation. Region II (residues 77-90) exhibits a large amplitude motion, being highly flexible, both in the absence and presence of p53 or other inhibitors. MDM2 exhibits a scattered profile in the fastest modes of motion, while binding of p53 and inhibitors puts restraints on MDM2 domains, clearly distinguishing the kinetically hot regions. Mode shape analysis revealed that the α4 domain controls the size of the cleft by keeping the cleft narrow in unbound MDM2; and open in the bound states for proper penetration and binding of p53 and inhibitors, which points to the induced-fit mechanism of p53 binding. P53 interacts with α2 and α4 in a synchronized manner. Collective modes are shifted upon inhibitor binding, i.e., second mode characteristic motion in MDM2-p53 complex is observed in the first mode of apo MDM2; however, apo and bound MDM2 exhibits similar features in the softest modes pointing to pre-existing modes facilitating the ligand binding. Although much higher amplitude motions are attained in the presence of non-peptide small molecule inhibitor molecules as compared to p53, they demonstrate close similarity. Hence, NVP-CGM097 and HDM201 succeed in mimicking the p53 behavior well. Elucidating how drug candidates alter the MDM2 global and conformational dynamics would shed light on the rational design of novel anticancer drugs.

Keywords: cancer, drug design, elastic network model, MDM2

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Authors: Gadia Duhita, Noorhana, Tjhin Wiguna

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Background: ADHD is the most common behavioural disorder in Indonesia. A stimulant, specifically methylphenidate, has been the first drug of choice for an ADHD treatment more than half a century. During the last decade, non-stimulant therapy (atomoxetine) for ADHD treatment has been developing. Growing evidence of its efficacy and the difference in its side effects profile to stimulant therapy have made methylphenidate’s position as a first line therapy for ADHD in need of re-evaluation. Both methylphenidate and atomoxetine have proven themselves against placebos in reducing core symptoms of ADHD. More recent studies directly compare the efficacy of methylphenidate and atomoxetine. Objective: The objective of this paper is to find out if either methylphenidate or atomoxetine is superior to another. This paper will assess the validity, importance, and applicability of current available evidence which compare the effectivity, efficacy, and safety of methylphenidate to atomoxetine for treatment in children and adolescents with ADHD. Method: The articles were searched for through the PubMed and Cochrane databases with “attention deficit/hyperactivity disorder OR adhd”, “methylphenidate”, and “atomoxetine” as the search keywords. Two articles which were relevant and eligible were chosen by using inclusion and exclusion criterias to be critically appraised. Result: The study by Hazel et al. showed that the efficacy of methylphenidate and atomoxetine are comparable for treatment in child and adolescent ADHD. The result shows 53.6% (95% CI 48.5%-58.4%) of the patient responded to the treatment by atomoxetine and 54.4% (95% CI 47.6%-61.1%) patients responded to methylphenidate, with the difference in proportion of–0.9% (95% CI –9.2%-7.5%). The other study by Hanwella et al. also showed that the efficacy of atomoxetine was not inferior to metilphenidate (SMD = 0.09, 95% CI –0.08-0.26) (Z = 1.06, p = 0.29). However, the sub-group analysis showed that OROS methylphenidate is more effective compared to atomoxetine (SMD = 0.32, 95% CI 0.12-0.53) (Z = 3.05, p < 0.02). Conclusion: The efficacy of methylphenidate and atomoxetine in reducing symptoms of ADHD is comparable. None is proven inferior to another. The choice of pharmacological tratment children and adolescents with ADHD should be made based on contraindication and the side effects profile of each drug.

Keywords: attention deficit/hyperactivity disorder, ADHD, atomoxetine, methylphenidate

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Authors: Mohammad Mushir Khan, C. Satyanarayana

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Education is considered as one of the prime bottlenecks in the economic growth of India. The Ministry of Human Resource & Development, Government of India has, therefore, given special attention to this issue and the Gross Enrollment Ratio (GER) in Higher Education has increased marginally during last five years, with the efforts and various policy decisions like Right to Education (RTE) and other fee reimbursement schemes, initiated by the State Governments. But still this is one of the lowest, if assessed at the global level. It is true that the GER has improved but the survey reveals that the quality has been badly affected. This paper tries to assess the impact of lack of quality education in various sectors that affects Indian Economy and thereby signifies the need of immediate policy decision at the government level. It is to be noted that in higher education, science, management, engineering and technology plays vital role as far as shaping country’s economy is concerned and as such the quality needs to be addressed, particularly, in these streams. The paper, after carefully studying lots of survey reports and other government/ non-government documents recommends measures to be initiated by the Central Government, on priority, for improving quality of education. The quality up-gradation in higher education single handedly provides real fuel to the India’s growth Engine, as it has potential to touch each and every sector that strengthens country’s economy.

Keywords: higher education, economy, accreditation, industry, technology

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Authors: Samuel Escandón, María J. Peñaherrera-Vélez, Signe Vargas-Rosvik, Carlos Jerves Córdova, Ximena Vélez-Calvo, Angélica Ochoa-Avilés

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Overweight and obesity are considered risk factors in childhood for developing nutrition-related non-communicable diseases (NCDs), such as diabetes, cardiovascular diseases, and cancer. In Ecuador, 35.4% of 5- to 11-year-olds and 29.6% of 12- to 19-year-olds are overweight or obese. Globally, unhealthy food environments characterized by high consumption of processed/ultra-processed food and rapid urbanization are highly related to the increasing nutrition-related non-communicable diseases. The evidence shows that in low- and middle-income countries (LMICs), fiscal policies and regulatory measures significantly reduce unhealthy food environments, achieving substantial advances in health. However, in some LMICs, little is known about the impact of governments' action to implement healthy food-environment policies. This study aimed to generate evidence on the state of implementation of public policy focused on food environments for the prevention of overweight and obesity in children and adolescents in Ecuador compared to global best practices and to target key recommendations for reinforcing the current strategies. After adapting the INFORMAS' Healthy Food Environment Policy Index (Food‐EPI) to the Ecuadorian context, the Policy and Infrastructure support components were assessed. Individual online interviews were performed using fifty-one indicators to analyze the level of implementation of policies directly or indirectly related to preventing overweight and obesity in children and adolescents compared to international best practices. Additionally, a participatory workshop was conducted to identify the critical indicators and generate recommendations to reinforce or improve the political action around them. In total, 17 government and non-government experts were consulted. From 51 assessed indicators, only the one corresponding to the nutritional information and ingredients labelling registered an implementation level higher than 60% (67%) compared to the best international practices. Among the 17 indicators determined as priorities by the participants, those corresponding to the provision of local products in school meals and the limitation of unhealthy-products promotion in traditional and digital media had the lowest level of implementation (34% and 11%, respectively) compared to global best practices. The participants identified more barriers (e.g., lack of continuity of effective policies across government administrations) than facilitators (e.g., growing interest from the Ministry of Environment because of the eating-behavior environmental impact) for Ecuador to move closer to the best international practices. Finally, within the participants' recommendations, we highlight the need for policy-evaluation systems, information transparency on the impact of the policies, transformation of successful strategies into laws or regulations to make them mandatory, and regulation of power and influence from the food industry (conflicts of interest). Actions focused on promoting a more active role of society in the stages of policy formation and achieving more articulated actions between the different government levels/institutions for implementing the policy are necessary to generate a noteworthy impact on preventing overweight and obesity in children and adolescents. Including systems for internal evaluation of existing strategies to strengthen successful actions, create policies to fill existing gaps and reform policies that do not generate significant impact should be a priority for the Ecuadorian government to improve the country's food environments.

Keywords: children and adolescents, food-EPI, food policies, healthy food environment

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Authors: Ricardo Pinto Mario Covele, Patricio V. Langa, Patrick Swanzy

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The English language has been recognized as a universal medium of instruction in academia, especially in Higher Education Institutions (HEIs) hence exerting enormous influence within the context of research and publication. By extension, the English Language has been embraced by scholars from non-English speaking countries. The purpose of this review was to synthesize the discussions using four databases. Discussion in the English language in the career development of academics, particularly in non-English speaking universities, is largely less visible. This paper seeks to fill this gap and to improve the visibility of the English language in the career development of academics focusing on non-English language speaking universities by undertaking a systematic literature review. More specifically, the paper addresses the language policy, English language learning model as a second language, sociolinguistic field and career development, methods, as well as its main findings. This review analyzed 75 relevant resources sourced from Western Cape’s Library, Scopus, Google scholar, and web of science databases from November 2020 to July 2021 using the PQRS framework as an analytical lens. The paper’s findings demonstrate that, while higher education continues to be under-challenges of English language usage, literature targeting non-English speaking universities remains less discussed than it is often described. The findings also demonstrate the dominance of English language policy, both for knowledge production and dissemination of literature challenging emerging scholars from non-English speaking HEIs. Hence, the paper argues for the need to reconsider the context of non-English language speakers in the English language in the career development of academics’ research, both as empirical fields and as emerging knowledge producers. More importantly, the study reveals two bodies of literature: (1) the instrumentalist approach to English Language learning and (2) Intercultural approach to the English Language for career opportunities, classified as the appropriate to explain the English language learning process and how is it perceived towards scholars’ academic careers in HEIs.

Keywords: English language, public and private universities, language policy, career development, non-English speaking countries

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Authors: Akhtar Aman, Abida Raza, Shumaila Bashir, Javaid Irfan, Andreas G. Schätzlein, Ijeoma F Uchegbeu

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Development of efficient delivery system for hydrophobic drugs remains a major concern in chemotherapy. The objective of the current study was to develop polymeric drug-delivery system for etoposide from amphiphilic derivatives of glycol chitosan, capable to improve the pharmacokinetics and to reduce the adverse effects of etoposide due to various organic solvents used in commercial formulations for solubilisation of etoposide. As a promising carrier, amphiphilic derivatives of glycol chitosan were synthesized by chemical grafting of palmitic acid N-hydroxy succinimide and quaternisation to glycol chitosan backbone. To this end a 7.9 kDa glycol chitosan was modified by palmitoylation and quaternisation into 13 kDa. Nano sized micelles prepared from this amphiphilic polymer had the capability to encapsulate up to 3 mg/ml etoposide. The pharmacokinetic results indicated that GCPQ based etoposide formulation transformed the biodistribution pattern. AUC 0.5-24 hr showed statistically significant difference in ETP-GCPQ vs. commercial preparation in liver (25 vs 70, p<0.001), spleen (27 vs. 36, P<0.05), lungs (42 vs. 136, p<0.001), kidneys (25 vs. 30, p<0.05) and brain (19 vs. 9,p<0.001). Using the hydrophobic fluorescent dye Nile red, we showed that micelles efficiently delivered their payload to MCF7 and A2780 cancer cells in-vitro and to A431 xenograft tumor in-vivo, suggesting these systems could deliver hydrophobic anti- cancer drugs such as etoposide to tumors. The pharmacokinetic results indicated that the GCPQ micelles transformed the biodistribution pattern and increased etoposide concentration in the brain significantly compared to free drug after intravenous administration. GCPQ based formulations not only reduced side effects associated with current available formulations but also increased their transport through the biological barriers, thus making it a good delivery system.

Keywords: glycol chitosan, Nile red, micelles, etoposide, A431 xenografts

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Authors: Bikram Jung Kunwar, Pralhad Kunwor

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The Community-Based Forest Management (CBFM) approach is often glorified as the best forest management alternatives in the developing countries. However, how the approach has been understood by the local user households, who implement it is remained unanswered for many planners, policy makers, and sometimes researcher as well. The study attempts to assess the understanding of ecology and economics of CBFM in Nepal, where community forest program has been implemented since the 1970s. In order to understand the impacts of the program, eight criteria and sixteen indicators for ecological conservation and similarly same number of criteria and indicators for socio-economic impacts of the program were designed and compared between before and after the program implementation. The community forestry program has positive effects in forest ecology conservation and at the same time rural livelihood improvement of local people. The study revealed that collective understanding of forest ecology and economics leads the CBFM approach towards the sustainability of the program in a win-win situation. The recommendations of the study are expected to be useful to natural resource managers, planners, and policy makers.

Keywords: community, forest management, ecology, economics, Nepal

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Authors: Wann-Ming Wey

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In today's popularity and progress of information technology, the big data set and its analysis are no longer a major conundrum. Now, we could not only use the relevant big data to analysis and emulate the possible status of urban development in the near future, but also provide more comprehensive and reasonable policy implementation basis for government units or decision-makers via the analysis and emulation results as mentioned above. In this research, we set Taipei City as the research scope, and use the relevant big data variables (e.g., population, facility utilization and related social policy ratings) and Analytic Network Process (ANP) approach to implement in-depth research and discussion for the possible reduction of land use in primary and secondary schools of Taipei City. In addition to enhance the prosperous urban activities for the urban public facility utilization, the final results of this research could help improve the efficiency of urban land use in the future. Furthermore, the assessment model and research framework established in this research also provide a good reference for schools or other public facilities land use and adaptive reuse strategies in the future.

Keywords: adaptive reuse, analytic network process, big data, land use strategy

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Authors: Romisaa Ali

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This paper presents a comparison between twin-delayed Deep Deterministic Policy Gradient (TD3) and Soft Actor-Critic (SAC) reinforcement learning algorithms in the context of training robust navigation policies for Jackal robots. By leveraging an open-source framework and custom motion control environments, the study evaluates the performance, robustness, and transferability of the trained policies across a range of scenarios. The primary focus of the experiments is to assess the training process, the adaptability of the algorithms, and the robot’s ability to navigate in previously unseen environments. Moreover, the paper examines the influence of varying environmental complexities on the learning process and the generalization capabilities of the resulting policies. The results of this study aim to inform and guide the development of more efficient and practical reinforcement learning-based navigation policies for Jackal robots in real-world scenarios.

Keywords: Jackal robot environments, reinforcement learning, TD3, SAC, robust navigation, transferability, custom environment

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Authors: Farshad Zeinali, Sajedeh Norouzi, Nader Mokari, Eduard Jorswieck

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The capacity of fifth-generation (5G) vehicle-to-everything (V2X) networks poses significant challenges. To ad- dress this challenge, this paper utilizes New Radio (NR) and New Radio Unlicensed (NR-U) networks to develop a heterogeneous vehicular network (HetNet). We propose a new framework, named joint BS assignment and resource allocation (JBSRA) for mobile V2X users and also consider coexistence schemes based on flexible duty cycle (DC) mechanism for unlicensed bands. Our objective is to maximize the average throughput of vehicles while guaranteeing the WiFi users' throughput. In simulations based on deep reinforcement learning (DRL) algorithms such as deep deterministic policy gradient (DDPG) and deep Q network (DQN), our proposed framework outperforms existing solutions that rely on fixed DC or schemes without consideration of unlicensed bands.

Keywords: vehicle-to-everything (V2X), resource allocation, BS assignment, new radio (NR), new radio unlicensed (NR-U), coexistence NR-U and WiFi, deep deterministic policy gradient (DDPG), deep Q-network (DQN), joint BS assignment and resource allocation (JBSRA), duty cycle mechanism

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Authors: Nasir Haruna Soba

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In addition to sustaining poverty and inequality, the issue of out-of-school children impedes efforts to accomplish the sustainable development goals (SDGs), especially Goal 4, which is to guarantee inclusive, egalitarian, and high-quality education for everyone. However, a number of social, cultural, and infrastructure barriers mean that millions of children in Nigeria are denied this privilege. This paper presents the findings of a case study conducted in Nigeria. The findings of this study revealed that out of school children in Nigeria are the most common causes of poverty; inadequate school facilities, long distances to schools, and poor road networks make it difficult for children, especially in rural areas, to access education. Social Disparities: Social inequality is sustained by differences in education, especially when it comes to financing, governance, and coordination amongst stakeholders. These differences are especially pronounced along gender and socioeconomic lines. The study recommended that policymakers and stakeholders should consider addressing the root causes, enhancing existing interventions, and implementing targeted policy measures. Nigeria can make significant strides towards ensuring inclusive and quality education for all children, thereby fostering sustainable development and reducing poverty.

Keywords: poverty, inequality, funding, education, development

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Authors: M. Kosandi, V. Susanti, N. I. Subono, E. Kartini

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This paper discusses the risk of glorification trap in combating human trafficking, as it is shown in the case of Indonesia. Based on a research on Indonesian combat against trafficking in 2017-2018, this paper shows the tendency of misinterpretation and misapplication of the Indonesian anti-trafficking law into misusing the law for glorification, to create an image of certain extent of achievement in combating human trafficking. The objective of this paper is to explain the persistent occurrence of human trafficking crimes despite the significant progress of anti-trafficking efforts of Indonesian government. The research was conducted in 2017-2018 by qualitative approach through observation, depth interviews, discourse analysis, and document study, applying the three-dimensional model for analyzing human trafficking in the source country. This paper argues that the drive for glorification of achievement in the combat against trafficking has trapped Indonesian government in the loop of misinterpretation, misapplication, and misuse of the anti-trafficking law. In return, the so-called crime against humanity remains high and tends to increase in Indonesia.

Keywords: human trafficking, anti-trafficking policy, transnational crime, source country, glorification trap

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Authors: Edy Wahyu Susilo

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This research discusses a comparative analysis of various anti-corruption responses of three Indonesian City Governments (Jakarta, Surabaya, and Medan) and completes previous findings on the effectiveness of the city anti-corruption program. Some factors (transparency, accountability, leadership, law enforcement, and bureaucratic reform) have been chosen in this study to diagnose the main role in the success and the failure of anti-corruption programs in these cities. These factors diagnose the relationship between factors and their dominancy, which is then utilized to create the city’s strategic anti-corruption programs. Although this study found leadership had a dominant influence both in encouraging and discouraging the performance of city transformation drastically, however, it is not the only factor that determined the performance of the city in the fight against corruption. It needs other factors as an ideal balancing element to achieve an anti-corruption program, namely KPK’s intervention and public engagement. Based on the dominance factors found, this research then develops an appropriate strategy using a policy evaluation approach to create a real practical guide regardless of the existence of good or bad leadership in the city. This research is expected to be a useful reference for stakeholders, especially the government, as a blueprint to prevent corruption by considering several important steps and guidance in efforts to eradicate corruption in the city, especially in Indonesia.

Keywords: intervention, KPK (corruption eradication commission), law enforcements, leadership, policy evaluation

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Authors: Desiree Vandenberghe, Johan Albrecht

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Non-communicable diseases (NCDs) are responsible for the vast majority of deaths in the European Union (EU) and represent a large share of total health care spending. A future increase in this health and financial burden is likely to be driven by population ageing, lifestyle changes and technological advances in medicine. Without adequate prevention measures, this burden can severely threaten population health and economic development. To tackle this challenge, a correct assessment of the current burden of NCDs is required, as well as a projection of potential increases of this burden. The contribution of this paper is to offer perspective on the evolution of the NCD burden towards the future and to give an indication of the potential of prevention policy. A Non-Homogenous, Semi-Markov model for the EU was constructed, which allowed for a projection of the cost burden for the four main NCDs (cancer, cardiovascular disease, chronic respiratory disease and diabetes mellitus) towards 2030 and 2050. This simulation is done based on multiple baseline scenarios that vary in demand and supply factors such as health status, population structure, and technological advances. Finally, in order to assess the potential of preventive measures to curb the cost explosion of NCDs, a simulation is executed which includes increased efforts for preventive health care measures. According to the Markov model, by 2030 and 2050, total costs (direct and indirect costs) in the EU could increase by 30.1% and 44.1% respectively, compared to 2015 levels. An ambitious prevention policy framework for NCDs will be required if the EU wants to meet this challenge of rising costs. To conclude, significant cost increases due to Non-Communicable Diseases are likely to occur due to demographic and lifestyle changes. Nevertheless, an ambitious prevention program throughout the EU can aid in making this cost burden manageable for future generations.

Keywords: non-communicable diseases, preventive health care, health policy, Markov model, scenario analysis

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