Search results for: drug policy

Authors: A. Abbou, V. Makis, N. Salari

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We study the condition-based maintenance (CBM) problem of a system subject to stochastic deterioration. The system is composed of three units (or modules): (i) Module 1 deterioration follows a Markov process with two operational states and one failure state. The operational states are partially observable through periodic condition monitoring. (ii) Module 2 deterioration follows a Gamma process with a known failure threshold. The deterioration level of this module is fully observable through periodic inspections. (iii) Only the operating age information is available of Module 3. The lifetime of this module has a general distribution. A CBM policy prescribes when to initiate a maintenance intervention and which modules to repair during intervention. Our objective is to determine the optimal CBM policy minimizing the long-run expected average cost of operating the system. This is achieved by formulating a Markov decision process (MDP) and developing the value iteration algorithm for solving the MDP. We provide numerical examples illustrating the cost-effectiveness of the optimal CBM policy through a comparison with heuristic policies commonly found in the literature.

Keywords: reliability, maintenance optimization, Markov decision process, heuristics

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Authors: Saurabh B. Ganorkar, Atul A. Shirkhedkar

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The need for investigations protecting against toxic impurities though seems to be a primary requirement; the impurities which may prove non - toxic can be explored for their therapeutic potential if any to assist advanced drug discovery. The essential role of pharmaceutical analysis can thus be extended effectively to achieve it. The present study successfully achieved these objectives with characterization of major degradation products as impurities for Zileuton which has been used for to treat asthma since years. The forced degradation studies were performed to identify the potential degradation products using Ultra-fine Liquid-chromatography. Liquid-chromatography-Mass spectrometry (Time of Flight) and Proton Nuclear Magnetic Resonance Studies were utilized effectively to characterize the drug along with five major oxidative and hydrolytic degradation products (DP’s). The mass fragments were identified for Zileuton and path for the degradation was investigated. The characterized DP’s were subjected to In-Silico studies as XP Molecular Docking to compare the gain or loss in binding affinity with 5-Lipooxygenase enzyme. One of the impurity of was found to have the binding affinity more than the drug itself indicating for its potential to be more bioactive as better Antiasthmatic. The close structural resemblance has the ability to potentiate or reduce bioactivity and or toxicity. The chances of being active biologically at other sites cannot be denied and the same is achieved to some extent by predictions for probability of being active with Prediction of Activity Spectrum for Substances (PASS) The impurities found to be bio-active as Antineoplastic, Antiallergic, and inhibitors of Complement Factor D. The toxicological abilities as Ames-Mutagenicity, Carcinogenicity, Developmental Toxicity and Skin Irritancy were evaluated using Toxicity Prediction by Komputer Assisted Technology (TOPKAT). Two of the impurities were found to be non-toxic as compared to original drug Zileuton. As the drugs are purposed and repurposed effectively the impurities can also be; as they can have more binding affinity; less toxicity and better ability to be bio-active at other biological targets.

Keywords: UFLC, LC-MS-TOF, NMR, Zileuton, impurities, toxicity, bio-activity

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Authors: Yogeeta O. Agrawal, Hitendra S. Mahajan, Sanjay J. Surana

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Methotrexate is effective in controlling recalcitrant psoriasis when administered by the oral or parenteral route long-term. However, the systematic use of this drug may provoke any of a number of side effects, notably hepatotoxic effects. To reduce these effects, clinical studies have been done with topical MTx. It is useful in treating a number of cutaneous conditions, including psoriasis. A major problem in topical administration of MTx currently available in market is that the drug is hydrosoluble and is mostly in the dissociated form at physiological pH. Its capacity for passive diffusion is thus limited. Localization of MTx in effected layers of skin is likely to improve the role of topical dosage form of the drug as a supplementary to oral therapy for treatment of psoriasis. One of the possibilities for increasing the penetration of drugs through the skin is the use of Nanostructured lipid Carriers. The objective of the present study was to formulate and characterize Methotrexate loaded Nanostructured Lipid Carriers (MtxNLCs), to understand in vitro drug release and evaluate the role of the developed gel in the topical treatment of psoriasis. MtxNLCs were prepared by solvent diffusion technique using 3(2) full factorial design.The mean diameter and surface morphology of MtxNLC was evaluated. MtxNLCs were lyophilized and crystallinity of NLC was characterized by Differential Scanning Calorimtery (DSC) and powder X-Ray Diffraction (XRD). The NLCs were incorporated in 1% w/w Carbopol 934 P gel base and in vitro skin deposition studies in Human Cadaver Skin were conducted. The optimized MtxNLCs were spherical in shape, with average particle size of 253(±9.92)nm, zeta potential of -30.4 (±0.86) mV and EE of 53.12(±1.54)%. DSC and XRD data confirmed the formation of NLCs. Significantly higher deposition of Methotrexate was found in human cadaver skin from MtxNLC gel (71.52 ±1.23%) as compared to Mtx plain gel (54.28±1.02%). Findings of the studies suggest that there is significant improvement in therapeutic index in treatment of psoriasis by MTx-NLCs incorporated gel base developed in this investigation over plain drug gel currently available in the market.

Keywords: methotrexate, psoriasis, NLCs, hepatotoxic effects

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Authors: Paraskevi Liosatou

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Climate change is considered to be of global concern being amplified by the fact that by its nature, cannot be spatially limited. This fact makes necessary the intergovernmental decision-making procedures. In the intergovernmental level, the institutions such as the United Nations Framework Convention on Climate Change and the Intergovernmental Panel on Climate Change develop efforts, methods, and practices in order to plan and suggest climate mitigation and adaptation measures. These measures are based on specific scientific findings and methods making clear the strong connection between science and policy. In particular, these scientific recommendations offer a series of practices, methods, and choices mitigating the problem by aiming at the indirect mitigation of the causes and the factors amplifying climate change. Moreover, modern production and economic context do not take into consideration the social, political, environmental and spatial dimensions of the problem. This work studies the decision-making process working in international and European level. In this context, this work considers the policy tools that have been implemented by various intergovernmental organizations. The methodology followed is based mainly on the critical study of standards and process concerning the connections and cooperation between science and policy as well as considering the skeptic debates developed. The finding of this work focuses on the links between science and policy developed by the institutional and scientific mechanisms concerning climate change mitigation. It also analyses the dimensions and the factors of the science-policy framework; in this way, it points out the causes that maintain skepticism in current scientific circles.

Keywords: climate change, climate change mitigation, climate change skepticism, IPCC, skepticism

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Authors: Abdul Matin, Muhammad Ajmal, Uzma Yunus, Noaman-ul Haq, Hafiz M. Shohaib, Ambreen G. Muazzam

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Carbon nanoparticles (CNPs) have unique properties that are useful for the diagnosis and treatment of cancer due to their precise properties like small size (ideal for delivery within the body) stability in solvent and tunable surface chemistry for targeted delivery. Here, highly fluorescent, monodispersed and water-soluble CNPs were synthesized directly from a suitable carbohydrate source (glucose and sucrose) by one-step acid assisted ultrasonic treatment at 35 KHz for 4 hours. This method is green, simple, rapid and economical and can be used for large scale production and applications. The average particle sizes of CNPs are less than 10nm and they emit bright and colorful green-blue fluorescence under the irradiation of UV-light at 365nm. The CNPs were characterized by scanning electron microscopy, fluorescent spectrophotometry, Fourier transform infrared spectrophotometry, ultraviolet-visible spectrophotometry and TGA analysis. Fluorescent CNPs were used as fluorescent probe and nano-carriers for anticancer drug. Functionalized CNPs (with ethylene diamine) were attached with anticancer drug-Methotrexate. In vitro bioactivity and biocompatibility of CNPs-drug conjugates was evaluated by LDH assay and Sulforhodamine B assay using human lung carcinoma cell lines (H157). Our results reveled that CNPs showed biocompatibility and CNPs-anticancer drug conjugates have shown potent cytotoxic effects and high antitumor activities in lung cancer cell lines. CNPs are proved to be excellent substitute for conventional drug delivery cargo systems and anticancer therapeutics in vitro. Our future studies will be more focused on using the same nanoparticles in vivo model system.

Keywords: carbon nanoparticles, carbon nanoparticles-methotrexate conjugates, human lung carcinoma cell lines, lactate dehydrogenase, methotrexate

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Authors: Abdulaziz Alakeel, Roaa Alamri, Abdulrahman Alomair, Mohammed Fouda

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Introduction: Ibrutinib is a selective, potent, and irreversible small-molecule inhibitor of Bruton's tyrosine kinase (BTK). It forms a covalent bond with a cysteine residue (CYS-481) at the active site of Btk, leading to inhibition of Btk enzymatic activity. The drug is indicated to treat certain type of cancers such as mantle cell lymphoma (MCL), chronic lymphocytic leukaemia and Waldenström's macroglobulinaemia (WM). Cardiac failure is a condition referred to inability of heart muscle to pump adequate blood to human body organs. There are multiple types of cardiac failure including left and right-sided heart failure, systolic and diastolic heart failures. The aim of this review is to evaluate the risk of cardiac failure associated with the use of ibrutinib and to suggest regulatory recommendations if required. Methodology: Signal Detection team at the National Pharmacovigilance Center (NPC) of Saudi Food and Drug Authority (SFDA) performed a comprehensive signal review using its national database as well as the World Health Organization (WHO) database (VigiBase), to retrieve related information for assessing the causality between cardiac failure and ibrutinib. We used the WHO- Uppsala Monitoring Centre (UMC) criteria as standard for assessing the causality of the reported cases. Results: Case Review: The number of resulted cases for the combined drug/adverse drug reaction are 212 global ICSRs as of July 2020. The reviewers have selected and assessed the causality for the well-documented ICSRs with completeness scores of 0.9 and above (35 ICSRs); the value 1.0 presents the highest score for best-written ICSRs. Among the reviewed cases, more than half of them provides supportive association (four probable and 15 possible cases). Data Mining: The disproportionality of the observed and the expected reporting rate for drug/adverse drug reaction pair is estimated using information component (IC), a tool developed by WHO-UMC to measure the reporting ratio. Positive IC reflects higher statistical association while negative values indicates less statistical association, considering the null value equal to zero. The results of (IC=1.5) revealed a positive statistical association for the drug/ADR combination, which means “Ibrutinib” with “Cardiac Failure” have been observed more than expected when compared to other medications available in WHO database. Conclusion: Health regulators and health care professionals must be aware for the potential risk of cardiac failure associated with ibrutinib and the monitoring of any signs or symptoms in treated patients is essential. The weighted cumulative evidences identified from causality assessment of the reported cases and data mining are sufficient to support a causal association between ibrutinib and cardiac failure.

Keywords: cardiac failure, drug safety, ibrutinib, pharmacovigilance, signal detection

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Authors: Jillian M. Hagel, Joseph E. Tucker, Peter J. Facchini

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With the aim of establishing a holistic approach for the treatment of central nervous system (CNS) disorders, we are pursuing a drug development program rapidly progressing through discovery and characterization phases. The drug candidates identified in this program are referred to as neuroplastogens owing to their ability to mediate neuroplasticity, which can be beneficial to patients suffering from anxiety, depression, or posttraumatic stress disorder. These and other related neuropsychiatric conditions are associated with the onset of neuronal atrophy, which is defined as a reduction in the number and/or productivity of neurons. The stimulation of neuroplasticity results in an increase in the connectivity between neurons and promotes the restoration of healthy brain function. We have synthesized a substantial catalogue of proprietary indolethylamine derivatives based on the general structures of serotonin (5-hydroxytryptamine) and psychedelic molecules such as N,N-dimethyltryptamine (DMT) and psilocin (4-hydroxy-DMT) that function as neuroplastogens. A primary objective in our screening protocol is the identification of derivatives associated with a significant reduction in hallucination, which will allow administration of the drug at a dose that induces neuroplasticity and triggers other efficacious outcomes in the treatment of targeted CNS disorders but which does not cause a psychedelic response in the patient. Both neuroplasticity and hallucination are associated with engagement of the 5HT2A receptor, requiring drug candidates differentially coupled to these two outcomes at a molecular level. We use novel and proprietary artificial intelligence algorithms to predict the mode of binding to the 5HT2A receptor, which has been shown to correlate with the hallucinogenic response. Hallucination is tested using the mouse head-twitch response model, whereas mouse marble-burying and sucrose preference assays are used to evaluate anxiolytic and anti-depressive potential. Neuroplasticity is assays using dendritic outgrowth assays and cell-based ELISA analysis. Pharmacokinetics and additional receptor-binding analyses also contribute the selection of lead candidates. A summary of the program is presented.

Keywords: neuroplastogen, non-hallucinogenic, drug development, anxiety, depression, PTSD, indolethylamine derivatives, psychedelic-inspired, 5-HT2A receptor, computational chemistry, head-twitch response behavioural model, neurite outgrowth assay

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Authors: Drago Jakovcevic, Mihovil Andelinovic, Igor Husak

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The aim of this paper is to explore the economic circumstances in which the selective credit policy, the least used instrument of four types of instruments on disposal to central banks, should be used. The most significant example includes the use of selective credit policies in response to the emergence of the global financial crisis by the FED. Specifics of the potential use of selective credit policies as the instigator of economic growth in Croatia, a small open economy, are determined by high euroization of financial system, fixed exchange rate and long-term trend growth of external debt that is related to the need to maintain high levels of foreign reserves. In such conditions, the classic forms of selective credit policies are unsuitable for the introduction. Several alternative approaches to implement selective credit policies are examined in this paper. Also, thorough analysis of distribution of selective monetary policy loans among economic sectors in Croatia is conducted in order to minimize the risk of investing funds and maximize the return, in order to influence the GDP growth.

Keywords: global crisis, selective credit policy, small open economy, Croatia

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Authors: V. Naga Sravan Kumar Varma, H. G. Shivakumar

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The aim of the study was to develop dual sensitive poly (N-isopropylacrylamide-co-acrylic acid) (PNA) nanogels(NGs) and studying its applications for Anti-Cancer therapy. NGs were fabricated by free radical polymerization using different amount of N-isopropylacrylamide and acrylic acid. A study for polymer composition over the effect on LCST in different pH was evaluated by measuring the absorbance at 500nm using UV spectrophotometer. Further selected NG’s were evaluated for change in hydrodynamic diameters in response to pH and temperature. NGs which could sharply respond to low pH value of cancer cells at body temperature were loaded with Fluorouracil (5-FU) using equilibrium swelling method and studied for drug release behaviour in different pH. A significant influence of NGs polymer composition over pH dependent LCST was observed. NGs which were spherical with an average particle size of 268nm at room temperature, shrinked forming an irregular shape when heated above to their respective LCST. 5FU loaded NGs did not intervene any difference in pH depended LCST behaviour of NGs. The in vitro drug release of NGs exhibited a pH and thermo-dependent control release. The cytoxicity study of blank carrier to MCF7 cell line showed no cytotoxicity. The results indicated that PNA NGs could be used as a potential drug carrier for anti-cancer therapy.

Keywords: pH and thermo-sensitive, nanogels, P(NIPAM-co-AAc), anti-cancer, 5-FU

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Authors: Swanand Pathak, Kiran R. Giri, Reena R. Giri, Kamlesh Palandurkar, Sangita Totade, Rajesh Jha, S. S. Patel

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Background: Population burden, illiteracy, availability of few doctors for larger group of population leads to many unanswered questions left in a patient’s mind. Incomplete information results into noncompliance, therapeutic failure, and adverse drug reactions (ADR). It is very important to establish a system which will provide noncommercial, independent, unbiased source of medicine information. Medicines Info OPD is a concept and step towards safe and appropriate use of medicines. Objective: (1) to assess the present status of knowledge about the medicines in the patients and its correlation with education; (2) to assess the medicine information dispensing modalities, their use and sufficiency from the patients view point; (3) to assess the overall need for Medicines Information OPD in present scenario. Materials and Methods: A pre-validated questionnaire based study was conducted amongst 500 patients of tertiary health care hospital. The questionnaire consisted of specific questions regarding understanding of prescription, knowledge about adverse drug reaction, view about self-medication and opinion regarding the need of Medicines Info OPD. Results: Significantly large proportion of patients opined that doctors do not have sufficient time in current Indian healthcare to explain the prescription and they are not aware of adverse drug reactions, expiry date or use the package inserts etc. Conclusion: Clinically relevant, up to date, user specific, independent, objective and unbiased Medicines Info OPD is essential for appropriate drug use and can help in a big way to common public to address many problems faced by them.

Keywords: information, prescription, unbiased, clinically relevant

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Authors: Giancarlo La Marca, Engy Shokry, Fabio Villanelli

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Epilepsy is one of the most common neurological disorders, with an estimated prevalence of 50 million people worldwide. Twenty five percent of the epilepsy population is represented in children under the age of 15 years. For antiepileptic drugs (AED), there is a poor correlation between plasma concentration and dose especially in children. This was attributed to greater pharmacokinetic variability than adults. Hence, therapeutic drug monitoring (TDM) is recommended in controlling toxicity while drug exposure is maintained. Carbamazepine (CBZ) is a first-line AED and the drug of first choice in trigeminal neuralgia. CBZ is metabolised in the liver into carbamazepine-10,11-epoxide (CBZE), its major metabolite which is equipotent. This develops the need for an assay able to monitor the levels of both CBZ and CBZE. The aim of the present study was to develop and validate a LC-MS/MS method for simultaneous quantification of CBZ and CBZE in dried blood spots (DBS). DBS technique overcomes many logistical problems, ethical issues and technical challenges faced by classical plasma sampling. LC-MS/MS has been regarded as superior technique over immunoassays and HPLC/UV methods owing to its better specificity and sensitivity, lack of interference or matrix effects. Our method combines advantages of DBS technique and LC-MS/MS in clinical practice. The extraction process was done using methanol-water-formic acid (80:20:0.1, v/v/v). The chromatographic elution was achieved by using a linear gradient with a mobile phase consisting of acetonitrile-water-0.1% formic acid at a flow rate of 0.50 mL/min. The method was linear over the range 1-40 mg/L and 0.25-20 mg/L for CBZ and CBZE respectively. The limit of quantification was 1.00 mg/L and 0.25 mg/L for CBZ and CBZE, respectively. Intra-day and inter-day assay precisions were found to be less than 6.5% and 11.8%. An evaluation of DBS technique was performed, including effect of extraction solvent, spot homogeneity and stability in DBS. Results from a comparison with the plasma assay are also presented. The novelty of the present work lies in being the first to quantify CBZ and its metabolite from only one 3.2 mm DBS disc finger-prick sample (3.3-3.4 µl blood) by LC-MS/MS in a 10 min. chromatographic run.

Keywords: carbamazepine, carbamazepine-10, 11-epoxide, dried blood spots, LC-MS/MS, therapeutic drug monitoring

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Authors: Ephraim Ugwu, Christopher Ehinomen

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Despite efforts by the Nigerian government to harmonize the macroeconomic policy implementations by establishing various committees to resolve disputes between the fiscal and monetary authorities, it is still evident that the federal government had continued its expansionary policy by increasing spending, thus creating huge budget deficit. This study evaluates the effect of macroeconomic policy coordination on economic growth uncertainty in Nigeria from 1980 to 2020. Employing the Auto regressive distributed lag (ARDL) bound testing procedures, the empirical results shows that the error correction term, ECM(-1), indicates a negative sign and is significant statistically with the t-statistic value of (-5.612882 ). Therefore, the gap between long run equilibrium value and the actual value of the dependent variable is corrected with speed of adjustment equal to 77% yearly. The long run coefficient results showed that the estimated coefficients of the intercept term indicates that other things remains the same (ceteris paribus), the economics growth uncertainty will continue reduce by 7.32%. The coefficient of the fiscal policy variable, PUBEXP, indicates a positive sign and significant statistically. This implies that as the government expenditure increases by 1%, economic growth uncertainty will increase by 1.67%. The coefficient of monetary policy variable MS also indicates a positive sign and insignificant statistically. The coefficients of merchandise trade variable, TRADE and exchange rate EXR show negative signs and significant statistically. This indicate that as the country’s merchandise trade and the rate of exchange increases by 1%, the economic growth uncertainty reduces by 0.38% and 0.06%, respectively. This study, therefore, advocate for proper coordination of monetary, fiscal and exchange rate policies in order to actualize the goal of achieving a stable economic growth.

Keywords: macroeconomic, policy coordination, growth uncertainty, ARDL, Nigeria

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Authors: Subrata Kar, Banani Kundu, Papiya Nandy, Ruma Basu, Sukhen Das

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Natural montmorilollite clay is a common ingredient in pharmaceutical products, both as excipients and active support; hence considered as suitable candidate for Drug Delivery System. In this work, cationic detergent CTAB is used to increase the interlayer spacing of Na+-Montmoriollite clay to intercalate curcumin and methotrexate. Methotrexate is a folic acid antagonist, anti-proliferative and immunosuppressive agent; while curcumin is a bioactive constituent of rhizomes of Curcuma longa, possessing remarkable chemo-preventive and anti-inflammatory properties. The resultant inorganic-organic hybrids are characterized by X-ray diffraction (XRD), Infrared spectroscopy (FTIR) and Thermo Gravimetric Analysis (TGA) to confirm successful intercalation of curcumin and Methotrexate within clay layers. Pharmaceutical investigation of the hybrids is explored by studying the drug loading (%), encapsulation efficiency and release kinetics. Finally in-vitro studies are performed using cancer cells to find the effect of released curcumin to improve the sensitivity of clay bound methotrexate to ameliorate cell death compared to their effectiveness when used without the inorganic aluminosilicate vehicle.

Keywords: montmorillonite, methotrexate, curcumin, loading efficiency, release kinetics, anticancer activity

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Authors: M. Moso-Diez, J. L. Moragues-Oregi, K. Simon-Elorz

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Innovation procurement is designed to steer the development of solutions towards concrete public sector needs as a driver for innovation from the demand side (in public services as well as in market opportunities for companies), is horizontally emerging as a new policy instrument. In 2014 the new EU public procurement directives 2014/24/EC and 2014/25/EC reinforced the support for Public Procurement for Innovation, dedicating funding instruments that can be used across all areas supported by Horizon 2020, and targeting potential buyers of innovative solutions: groups of public procurers with similar needs. Under this programme, new policy adapters and networks emerge, aiming to embed innovation criteria into new procurement processes. As these initiatives are in process, research related to is scarce. We argue that Innovation Public Procurement can arise as an innovative policy instrument to public procurement in different policy domains, in spite of existing institutional and cultural barriers (legal guarantee versus innovation). The presentation combines insights from public procurement to supply management chain management in a sustainability and innovation policy arena, as a means of providing understanding of: (1) the circumstances that emerge; (2) the relationship between public and private actors; and (3) the emerging capacities in the definition of the agenda. The policy adopters are the contracting authorities that mainly are at municipal level where they interact with the supply management chain, interconnecting sustainability and climate measures with other policy priorities such as innovation and urban planning; and through the Competitive Dialogue procedure. We found that geography and territory affect both the level of municipal budget (due to municipal income per capita) and its institutional competencies (due to demographic reasons). In spite of the relevance of institutional determinants for public procurement, other factors play an important role such as human factors as well as both public policy and private intervention. The experience is a ‘city project’ (Bilbao) in the field of brownfield decontamination. Brownfield sites typically refer to abandoned or underused industrial and commercial properties—such as old process plants, mining sites, and landfills—that are available but contain low levels of environmental contaminants that may complicate reuse or redevelopment of the land. This article concludes that Innovation Public Procurement in sustainability and climate issues should be further developed both as a policy instrument and as a policy research line that could enable further relevant changes in public procurement as well as in climate innovation.

Keywords: innovation, city projects, public policy, public procurement

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Authors: G. A. Kuanaliyeva, G. T. Aigarinova, G. K. Shulanbekova

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This article is devoted to judicial control in criminal legal proceedings of the Republic of Kazakhstan in the light of the new Concept of legal policy till 2020. In article the general characteristic and concept of judicial control, and also its signs and types are considered. Different views of scientists are analyzed. Foreign experiment on application of judicial control is given. The author states also the point sight on this problem and gives the definition to concept of judicial control. The code of criminal procedure of the Republic of Kazakhstan (RK Criminal Procedure Code) doesn't consolidate concept of judicial control. The author in article suggests making change and addition to the existing Code of criminal procedure of the Republic of Kazakhstan by definition of judicial control. The decree of the President of the Republic of Kazakhstan of August 24, 2009 No. 858 approved the Concept of legal policy of the Republic for the period from 2010 to 2020. The new Concept of legal policy of the Republic of Kazakhstan, defines prospects of development of national legal system of the country on the following decade. The concept of legal policy completely mentions also institute of judicial control. Since finding of the independence by Kazakhstan the set of laws, including the rights directed on providing, freedoms and a legitimate interest of citizens was accepted. Certainly, in any country, whatever democratic it was, there are problems to human rights. However, it is obvious that Kazakhstan strongly intends to guarantee all Republic of Kazakhstan proclaimed in the Constitution the rights and freedoms of the citizens. Our country seeks for creation of the constitutional state, tries to provide a guarantee from various arbitrariness in activity of competent government bodies, officials. In the concept of legal policy of the Republic of Kazakhstan it is specified: "...priority of development of the criminal procedure right there is a further consecutive realization of the fundamental principles of the criminal legal proceedings directed on protection of the rights and freedoms of the person". Judicial control just also is such guarantee.

Keywords: rights and freedoms of the person, concept, legal policy, court, judicial control

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Authors: Sarah P. Wuebbolt, Ashlee N. Sawyer-Mays

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Non-medical prescription and other drug (NMPOD) use has been a significant public health issue for the last few decades, with problematic use increasing among university students more recently. The current study focused on associations between NMPOD use and mental health, well-being, and world beliefs among young adults. Young adults (N=513) completed online questionnaires assessing stress, demographic characteristics, self-esteem, NMPOD use, coping mechanisms, and anxiety. A substantial portion of participants reported using cannabis (48.5%, n=249), while smaller portions of participants reported using stimulants (26.7%, n = 137), sedatives (17.2%, n=88), opioids (10.8%, n=55), and hallucinogens (14.4%, n=74). Five hierarchical logistic regressions were performed to determine the independent relationships between mental health, well-being, and world belief factors and NMPOD use for the five classes of substances. After controlling for demographic factors (age, gender, race/ethnicity, sexual orientation, and religious affiliation), depression was associated with increased non-medical stimulant, opioid, and cannabis use; coping self-efficacy was associated with increased hallucinogen use, and attendance of worship services was associated with decreased non-medical cannabis and hallucinogen use. Results suggest that depression was strongly associated with non-medical stimulant, opioid, and cannabis use, and attendance of worship services was protective against cannabis and hallucinogen use. To the best of our knowledge, this is one of the first studies to investigate the relationships between mental health, well-being, world beliefs, and NMPOD use among young adults. The present study illuminates future targets for intervention, such as increased access to mental health diagnosis and treatment and the exploration of the roles of religion and shared community in the prevention of drug use among young adults.

Keywords: cannabis, mental health, non-medical prescription and other drug use, world beliefs

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Authors: Krutika K. Sawant, Anil Solanki

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The present study deals with the preparation and optimization of ethyl cellulose-containing disopyramide phosphate loaded microspheres using solvent evaporation technique. A central composite design consisting of a two-level full factorial design superimposed on a star design was employed for optimizing the preparation microspheres. The drug:polymer ratio (X1) and speed of the stirrer (X2) were chosen as the independent variables. The cumulative release of the drug at a different time (2, 6, 10, 14, and 18 hr) was selected as the dependent variable. An optimum polynomial equation was generated for the prediction of the response variable at time 10 hr. Based on the results of multiple linear regression analysis and F statistics, it was concluded that sustained action can be obtained when X1 and X2 are kept at high levels. The X1X2 interaction was found to be statistically significant. The drug release pattern fitted the Higuchi model well. The data of a selected batch were subjected to an optimization study using Box-Behnken design, and an optimal formulation was fabricated. Good agreement was observed between the predicted and the observed dissolution profiles of the optimal formulation.

Keywords: disopyramide phosphate, ethyl cellulose, microspheres, controlled release, Box-Behnken design, factorial design

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Authors: Chee Wee Gan, Anthony Herr Cheun Ng, Yee Shan Wong, Subbu Venkatraman, Lynne Hsueh Yee Lim

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Otitis media with effusion (OME) is the leading cause of hearing loss in children worldwide. Surgery to insert grommet tube into the eardrum is usually indicated for OME unresponsive to antimicrobial therapy. It is the most common surgery for children. However, current commercially available grommet tubes are non-bioresorbable, not drug-treated, with unpredictable duration of retention on the eardrum to ventilate middle ear. Their functionality is impaired when clogged or chronically infected, requiring additional surgery to remove/reinsert grommet tubes. We envisaged that a novel fully bioresorbable grommet tube with sustained antibiotic release technology could address these drawbacks. In this study, drug-loaded bioresorbable poly(L-lactide-co-ε-caprolactone)(PLC) copolymer grommet tubes were fabricated by microinjection moulding technique. In vitro drug release and degradation model of PLC tubes were studied. Antibacterial property was evaluated by incubating PLC tubes with P. aeruginosa broth. Surface morphology was analyzed using scanning electron microscopy. A preliminary animal study was conducted using guinea pigs as an in vivo model to evaluate PLC tubes with and without drug, with commercial Mini Shah grommet tube as comparison. Our in vitro data showed sustained drug release over 3 months. All PLC tubes revealed exponential degradation profiles over time. Modeling predicted loss of tube functionality in water to be approximately 14 weeks and 17 weeks for PLC with and without drug, respectively. Generally, PLC tubes had less bacteria adherence, which were attributed to the much smoother tube surfaces compared to Mini Shah. Antibiotic from PLC tube further made bacteria adherence on surface negligible. They showed neither inflammation nor otorrhea after 18 weeks post-insertion in the eardrums of guinea pigs, but had demonstrated severe degree of bioresorption. Histology confirmed the new PLC tubes were biocompatible. Analyses on the PLC tubes in the eardrums showed bioresorption profiles close to our in vitro degradation models. The bioresorbable antibiotic-loaded grommet tubes showed good predictability in functionality. The smooth surface and sustained release technology reduced the risk of tube infection. Tube functional duration of 18 weeks allowed sufficient ventilation period to treat OME. Our ongoing studies include modifying the surface properties with protein coating, optimizing the drug dosage in the tubes to enhance their performances, evaluating their functional outcome on hearing after full resoption of grommet tube and healing of eardrums, and developing animal model with OME to further validate our in vitro models.

Keywords: bioresorbable polymer, drug release, grommet tube, guinea pigs, otitis media with effusion

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Authors: Victor Oyewumi Ogunbiyi

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Food waste is recognised as one of the major global challenges in achieving a sustainable future. Currently, very little is known about the multi-stakeholder approach to food waste management downstream of the supply chain, particularly in the foodservice sector. In order to better understand and explain the complex issues of food waste, a qualitative study was conducted on the generation of food waste in food services (restaurants, catering, canteens, and local food vendors) and policy initiatives to mitigate it from the perspective of the stakeholders. A semi-structured interview approach and observation were used to collect data from some 32 selected stakeholders in Garki, Abuja, Nigeria. Thematic analysis was employed to analyse the data from the qualitative instrument adopted in this study. Results revealed that the attitude of stakeholders, poor environmental hygiene, poor food cooking skills and handling, and lack of communication are the major causes of food waste. This study identified seven policy initiatives: regulations, information and education campaigns, economic instruments, mobile applications, stakeholders’ collaboration, firm internal action, and training. Finally, we link policy initiatives to food waste mitigation to provide a response to the damaging shock of food waste.

Keywords: food waste, foodservices, emerging opportunities, policy initiatives, food waste prevention, multistakeholder. garki district-abuja

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Authors: Mani Mofidi, Neda Valizadeh, Ali Hashemaghaee, Mona Hashemaghaee, Soudabeh Shafiee Ardestani

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Background: Acute pain and its management remained the most complaint of emergency service admission. Diagnostic and therapeutic procedures add to patients’ pain. Diminishing the pain increases the quality of patient’s feeling and improves the patient-physician relationship. Aim: The aim of this study was to evaluate the outcomes and side effects of opioid administration in emergency patients. Material and Methods: patients admitted to ward II emergency service of Imam Khomeini hospital, who received one of the opioids: morphine, pethidine, methadone or fentanyl as an analgesic were evaluated. Their vital signs and general condition were examined before and after drug injection. Also, patient’s pain experience were recorded as numerical rating score (NRS) before and after analgesic administration. Results: 268 patients were studied. 34 patients were addicted to opioid drugs. Morphine had the highest rate of prescription (86.2%), followed by pethidine (8.5%), methadone (3.3%) and fentanyl (1.68). While initial NRS did not show significant difference between addicted patients and non-addicted ones, NRS decline and its score after drug injection were significantly lower in addicted patients. All patients had slight but statistically significant lower respiratory rate, heart rate, blood pressure and O2 saturation. There was no significant difference between different kind of opioid prescription and its outcomes or side effects. Conclusion: Pain management should be always in physicians’ mind during emergency admissions. It should not be assumed that an addicted patient complaining of pain is malingering to receive drug. Titration of drug and close monitoring must be in the curriculum to prevent any hazardous side effects.

Keywords: numerical rating score, opioid, pain, emergency department

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Authors: S. Zeynep Siretioglu Girgin, Gizem Turna Cebeci

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Turkey’s immigration policy is a controversial issue considering its legal, economic, social, and political and human rights dimensions. Formulation of an immigration policy goes hand in hand with political processes, where natives’ attitudes play a significant role. On the other hand, as was the case in Turkey, radical changes made in immigration policy or policies lacking transparency may cause severe reactions by the host society. The underlying discussion paper aims to analyze quantitatively the effects of the existing ‘open door’ immigration policy on the economic integration of Syrian refugees in Turkey, and on the perception of the native population of refugees. For the analysis, semi-structured in-depth interviews and focus group interviews have been conducted. After the introduction, a literature review is provided, followed by theoretical background on the explanation of natives’ attitudes towards immigrants. In the next section, a qualitative analysis of natives’ attitudes towards Syrian refugees is presented with the subtopics of (i) awareness, general opinions and expectations, (ii) open-door policy and management of the migration process, (iii) perception of positive and negative impacts of immigration, (iv) economic integration, and (v) cultural similarity. Results indicate that, natives concurrently have social, economic and security concerns regarding refugees, while difficulties regarding security and economic integration of refugees stand out. Socio-economic characteristics of the respondents, such as the educational level and employment status, are not sufficient to explain the overall attitudes towards refugees, while they can be used to explain the awareness of the respondents and the priority of the concerns felt.

Keywords: economic integration, immigration policy, integration policies, migrants, natives’ sentiments, perception, Syrian refugees, Turkey

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Authors: Yung-Ching Chou, Albert Shangpao Yeh, Luke H. C. Hsiao

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Police used to be an honor job. However, the police are no longer concerned about the mission and public safety instead of the issue of retirement. The main reason is the amendment of 'Public Servants Retirement Act' in Taiwan was effective since January 2011. The purposes of change were to solve the problem of the financial crisis which caused by the Hugh deficit of the civil servants pension fund. The policy of the civil servants pension reform was not only seriously impact the motives of policy, but also negatively impact the workforce of police. This research conducted a secondary data of Baoanjingcha Fifth Police Corps during the period between 2011 and 2015. Secondly, the research interviewed six representatives from the retired police in order to explore the retirement motives. In short, there were several major findings and suggestions in the following: 1. The police won't choice to retire which the nature of task is simple. 2. The ranking level of positions positively correlated with the retired age of police. 3. The police officers who are categorized as 'hazardous work' first class personnel should decrease the standard of the retirement age and allow the option of a monthly pension. 4. The information of the retirees' rights, as well as protection, are correlated with the service as well professional of personnel officer. More findings, as well as suggestions, will be elaborated on the content of this paper.

Keywords: human resource management, pension policy change, police retirement rush, public servants retirement act

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Authors: Adel Nikfarjam, Hamed Tayebi, Sadoullah Ebrahimnejad

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This paper considers a two-echelon inventory system with a number of warehouses and a single retailer. The retailer replenishes its required items from warehouses, and assembles them into a single final product. We assume that each warehouse supplies only one kind of the raw material for the retailer. The demand process of the final product is assumed to be Poissson, and unsatisfied demand of the final product will be lost. The retailer applies one-for-one-period ordering policy which is also known as (1, T) ordering policy. In this policy the retailer orders to each warehouse a fixed quantity of each item at fixed time intervals, which the fixed quantity is equal to the utilization of the item in the final product. Since, this policy eliminates all demand uncertainties at the upstream echelon, the standard lot sizing model can be applied at all warehouses. In this paper, we calculate the total cost function of the inventory system. Then, based on this function, we present a procedure to obtain the optimal time interval between two consecutive order placements from retailer to the warehouses, and the optimal order quantities of warehouses (assuming that there are positive ordering costs at warehouses). Finally, we present some numerical examples, and conduct numerical sensitivity analysis for cost parameters.

Keywords: two-echelon supply chain, multi-vendor-single-buyer inventory system, lost sales, Poisson demand, one-for-one-period policy, lot sizing model

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Authors: Gagan Dhawan

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Mycobacterium tuberculosis was described as ‘captain of death’ with an inherent property of multiple drug resistance majorly caused by the competent mechanism of efflux pumps. In this study, various open source tools combining chemo-informatics with bioinformatics were used for efficient in-silico drug designing. The efflux pump, Rv1218c, belonging to the ABC transporter superfamily, which is predicted to be a tetronasin-transporter in M. tuberculosis was targeted. Recent studies have shown that Rv1218c forms a complex with two more efflux pumps (Rv1219c and Rv1217c) to provide multidrug resistance to the bacterium. The 3D structure of the protein was modeled (as the structure was unavailable in the previously collected databases on this gene). The TMHMM analysis of this protein in TubercuList has shown that this protein is present in the outer membrane of the bacterium. Virtual screening of compounds from various publically available chemical libraries was performed on the M. tuberculosis protein using various open source tools. These ligands were further assessed where various physicochemical properties were evaluated and analyzed. On comparison of different physicochemical properties, toxicity and docking, the ligand 2-(hydroxymethyl)-6-[4, 5, 6-trihydroxy-2-(hydroxymethyl) tetrahydropyran-3-yl] oxy-tetrahydropyran-3, 4, 5-triol was found to be best suited for further studies.

Keywords: drug resistance, efflux pump, molecular docking, virtual screening

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Authors: Syed Asif Hassan, Tabrej Khan

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Multiple sclerosis (MS) is a chronic demyelinating autoimmune disorder, of the central nervous system (CNS). In the present scenario, the current therapies either do not halt the progression of the disease or have side effects which limit the usage of current Disease Modifying Therapies (DMTs) for a longer period of time. Therefore, keeping the current treatment failure schema, we are focusing on screening novel analogues of the available DMTs that specifically bind and inhibit the Sphingosine1-phosphate receptor1 (S1PR1) thereby hindering the lymphocyte propagation toward CNS. The novel drug-like analogs molecule will decrease the frequency of relapses (recurrence of the symptoms associated with MS) with higher efficacy and lower toxicity to human system. In this study, an integrated approach involving ligand-based virtual screening protocol (Ultrafast Shape Recognition with CREDO Atom Types (USRCAT)) to identify the non-toxic drug like analogs of the approved DMTs were employed. The potency of the drug-like analog molecules to cross the Blood Brain Barrier (BBB) was estimated. Besides, molecular docking and simulation using Auto Dock Vina 1.1.2 and GOLD 3.01 were performed using the X-ray crystal structure of Mtb LprG protein to calculate the affinity and specificity of the analogs with the given LprG protein. The docking results were further confirmed by DSX (DrugScore eXtented), a robust program to evaluate the binding energy of ligands bound to the ligand binding domain of the Mtb LprG lipoprotein. The ligand, which has a higher hypothetical affinity, also has greater negative value. Further, the non-specific ligands were screened out using the structural filter proposed by Baell and Holloway. Based on the USRCAT, Lipinski’s values, toxicity and BBB analysis, the drug-like analogs of fingolimod and BG-12 showed that RTL and CHEMBL1771640, respectively are non-toxic and permeable to BBB. The successful docking and DSX analysis showed that RTL and CHEMBL1771640 could bind to the binding pocket of S1PR1 receptor protein of human with greater affinity than as compared to their parent compound (Fingolimod). In this study, we also found that all the drug-like analogs of the standard MS drugs passed the Bell and Holloway filter.

Keywords: antagonist, binding affinity, chemotherapeutics, drug-like, multiple sclerosis, S1PR1 receptor protein

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Authors: Reynaldo Esquivel, Pedro Hernandez, Aaron Martinez-Higareda, Sergio Tena-Cano, Enrique Alvarez-Ramos, Armando Lucero-Acuna

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Stimuli-responsive nanomaterials play an essential role in loading, transporting and well-distribution of anti-cancer compounds in the cellular surroundings. The outstanding properties as the Lower Critical Solution Temperature (LCST), hydrolytic cleavage and protonation/deprotonation cycle, govern the release and delivery mechanisms of payloads. In this contribution, we experimentally determine the load efficiency and release of antineoplastic Vincristine Sulfate into PNIPAM-Interpenetrated-Chitosan (PIntC) nanoparticles. Structural analysis was performed by Fourier Transform Infrared Spectroscopy (FT-IR) and Proton Nuclear Magnetic Resonance (1HNMR). ζ-Potential (ζ) and Hydrodynamic diameter (DH) measurements were monitored by Electrophoretic Mobility (EM) and Dynamic Light scattering (DLS) respectively. Mathematical analysis of the release pharmacokinetics reveals a three-phase model above LCST, while a monophasic of Vincristine release model was observed at 32 °C. Cytotoxic essays reveal a noticeable enhancement of Vincristine effectiveness at low drug concentration on HeLa cervix cancer and MDA-MB-231 breast cancer.

Keywords: nanoparticles, vincristine, drug delivery, PNIPAM

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Authors: Akinsola Oluwatosin, Udofia Samuel, Odofin Mayowa

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The study is aimed at assessing the Geographic Information System (GIS)-based spatial analysis of Survival Pattern and Treatment Outcomes of Multi-Drug Resistant Tuberculosis (MDR-TB) cases for Lagos, Nigeria, with an objective to inform priority areas for public health planning and resource allocation. Multi-drug resistant tuberculosis (MDR-TB) develops due to problems such as irregular drug supply, poor drug quality, inappropriate prescription, and poor adherence to treatment. The shapefile(s) for this study were already georeferenced to Minna datum. The patient’s information was acquired on MS Excel and later converted to . CSV file for easy processing to ArcMap from various hospitals. To superimpose the patient’s information the spatial data, the addresses was geocoded to generate the longitude and latitude of the patients. The database was used for the SQL query to the various pattern of the treatment. To show the pattern of disease spread, spatial autocorrelation analysis was used. The result was displayed in a graphical format showing the areas of dispersing, random and clustered of patients in the study area. Hot and cold spot analysis was analyzed to show high-density areas. The distance between these patients and the closest health facility was examined using the buffer analysis. The result shows that 22% of the points were successfully matched, while 15% were tied. However, the result table shows that a greater percentage of it was unmatched; this is evident in the fact that most of the streets within the State are unnamed, and then again, most of the patients are likely to supply the wrong addresses. MDR-TB patients of all age groups are concentrated within Lagos-Mainland, Shomolu, Mushin, Surulere, Oshodi-Isolo, and Ifelodun LGAs. MDR-TB patients between the age group of 30-47 years had the highest number and were identified to be about 184 in number. The outcome of patients on ART treatment revealed that a high number of patients (300) were not ART treatment while a paltry 45 patients were on ART treatment. The result shows the Z-score of the distribution is greater than 1 (>2.58), which means that the distribution is highly clustered at a significance level of 0.01.

Keywords: tuberculosis, patients, treatment, GIS, MDR-TB

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Authors: Kaida Kobylka

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Museum education policy can be developed through the lens of radical democracy and radically democratic relational aesthetics to provoke a more wholistic, agonistic, and utopian educational experiences that expand a viewer’s experiences and knowledge of artwork in a museum’s permanent collection to encourage a deeper understanding of art and the community of a museum’s connections to equity, diversity, inclusion, and decolonization. Practices used by the museum will create cohesive and engaging informal education that utilizes community-based, alternative knowledge and create dignity-safe spaces for viewers to engage critically with the visual objects.

Keywords: museum education, radical democracy, Canadian policy, community-based knowledge

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Authors: Badoiu Mihaela Catalina

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Main focus of COHESION policy was reducing social and economic disparities between member states and regions, sustainable development and equal opportunities. In this perspective, the present study intend to analyze the evolution of the European architecture and its direct impact over the real convergence in the member states.

Keywords: cooperation, European union, member states, cohesion policy

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Authors: Sanchayan Banerjee, Peter John

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Nudge plus is a modification of the toolkit of behavioural public policy. It incorporates an element of reflection¾the plus¾into the delivery of a nudge, either blended in or made proximate. Nudge plus builds on recent work combining heuristics and deliberation. It may be used to design pro-social interventions that help preserve the autonomy of the agent. The argument turns on seminal work on dual systems, which presents a subtler relationship between fast and slow thinking than commonly assumed in the classic literature in behavioural public policy. We review classic and recent work on dual processes to show that a hybrid is more plausible than the default interventionist or parallel competitive framework. We define nudge plus, set out what reflection could entail, provide examples, outline causal mechanisms, and draw testable implications.

Keywords: nudge, nudge plus, think, dual process theory

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