Search results for: access to drugs

Authors: Nirmala Gopal, Sheetal Bhoola, Audecious Mugwagwa

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This paper discusses the continued infringement and exploitation of data by non-state actors for destructive purposes, emphasizing radical terrorist organizations. It will discuss how terrorist organizations access and use data to foster their nefarious agendas. It further examines how cybersecurity, designed as a tool to curb data exploitation, is ineffective in raising global citizens' concerns about how their data can be kept safe and used for its acquired purpose. The study interrogates several policies and data protection instruments, such as the Data Protection Act, Cyber Security Policies, Protection of Personal Information(PPI) and General Data Protection Regulations (GDPR), to understand data use and storage in democratic states. The study outcomes point to the fact that international cybersecurity and cybercrime legislation, policies, and conventions have not curbed violations of data access and use by radical terrorist groups. The study recommends ways to enhance cybersecurity and reduce cyber risks using democratic principles.

Keywords: cybersecurity, data exploitation, terrorist organizations, data democracy

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Authors: Anoosh Eghdami

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Background and aim: Conventional anticancer drugs display significant shortcomings which limit their use in cancer therapy. For this reason, important progress has been achieved in the field of nanotechnology to solve these problems and offer a promising and effective alternative for cancer treatment. Tumor markers may also be measured periodically during cancer therapy. Tumor markers may also be measured after treatment has ended to check for recurrence the return of cancer. The aim of this study was to evaluate the effect of nano drug delivery in induced breast cancer with DMBA by using CA15-3 tumor marker. Material and method: the rats were divided into five groups. The first group (control n=15) were fed only sesame oil as a gavage. In the second group n=15,10 mg DMBA was dissolved in 5ml of sesame oil and were fed as a gavage. In addition to DMBA treatment as the second group, in the 3,4and 5 groups after cancer creation, respectively affected by alpha interferon (α-IFN),alpha interferon conjugated with single walled carbon nano tube (α-IFN-SWNT) and encapsulated in poly lactic poly glycolic acid (α-IFN-PLGA). Tumor marker was measured in recent three groups. Results: The ANOVA test was used to determine the differences among the groups. Cancer inducing in rats (group 2) caused a significant increase in blood levels of CA15-3 (P<0.05). Administration of α-IFN, α-IFN –SWNT and α-IFN-PLGA in 3 groups of cancerous rats caused a significant decrease in blood levels of CA15-3 only the group that treated with α-IFN-PLGA (p<0.05). Conclusion: the results of this study indicate that nano drugs more effective than traditional drug in cancer treatment, although further work is needed to elucidate the safety and side effect of these compound in human.

Keywords: breast cancer, nano drug, tumor markers, CA15-3, α-IFN-PLGA, -IFN –SWNT

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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: Babak Mohajeri

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In recent years, the conventional business model of ownership has been changed towards accessibility in a variety of markets. Two trends can be observed in the evolution of this rental-like business model. Firstly, the technological development that enables the emergence of new business models. These new business models increasingly become agile and flexible. For example Spotify, an online music stream company provides consumers access to over millions of music tracks, conveniently through the smartphone, tablet or computer. Similarly, Car2Go, the car sharing company accesses its members with flexible and nearby sharing cars. The second trend is the increasing communication and connections via social networks. This trend enables a shift to peer-to-peer accessibility based business models. Conventionally, companies provide access for their customers to own companies products or services. In peer-to-peer model, nonetheless, companies facilitate access and connection across their customers to use other customers owned property or skills, competencies or services .The is so-called the sharing economy business model. The aim of this study is to investigate into a new and emerging type of the sharing economy model in which role of customers and service providers may dramatically change. This new model is called Collaborative Service Networks. We propose a mechanism for Collaborative Service Networks business model. Uber and Airbnb, two successful growing companies, have been selected for our case studies and their business models are analyzed. Finally, we study the emergence of the collaborative service networks in the manufacturing domain. Our finding results to a new manufacturing paradigm called social manufacturing.

Keywords: sharing economy, collaborative service networks, social manufacturing, manufacturing development

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Authors: Kaddi Mohammed, A. Benatiallah, D. Benatiallah

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Data grid is a technology that has full emergence of new challenges, such as the heterogeneity and availability of various resources and geographically distributed, fast data access, minimizing latency and fault tolerance. Researchers interested in this technology address the problems of the various systems related to the industry such as task scheduling, load balancing and replication. The latter is an effective solution to achieve good performance in terms of data access and grid resources and better availability of data cost. In a system with duplication, a coherence protocol is used to impose some degree of synchronization between the various copies and impose some order on updates. In this project, we present an approach for placing replicas to minimize the cost of response of requests to read or write, and we implement our model in a simulation environment. The placement techniques are based on a cost model which depends on several factors, such as bandwidth, data size and storage nodes.

Keywords: response time, query, consistency, bandwidth, storage capacity, CERN

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Authors: Sajedeh Salehi, Marco Giacalone

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This paper examines the role of existing online dispute resolution (ODR) mechanisms and their effects on ameliorating access to justice – as a protected right by Art. 47 of the EU Charter of Fundamental Rights – for consumers in EU. The major focus of this study will be on evaluating ODR as the means of dispute resolution for Business-to-Consumer (B2C) cross-border small claims raised in e-commerce transactions. The authors will elaborate the consequences of implementing ODR methods in the context of recent developments in EU regulatory safeguards on promoting consumer protection. In this analysis, both non-judiciary and judiciary ODR redress mechanisms are considered, however, the significant consideration is given to – obligatory and non-obligatory – judiciary ODR methods. For that purpose, this paper will particularly investigate the impact of the EU ODR platform as well as the European Small Claims Procedure (ESCP) Regulation 861/2007 and their role on accelerating the access to justice for consumers in B2C e-disputes. Although, considerable volume of research has been carried out on ODR for consumer claims, rather less (or no-) attention has been paid to provide a combined doctrinal and empirical evaluation of ODR’s potential in resolving cross-border small e-disputes, in EU. Hence, the methodological approach taken in this study is a mixed methodology based on qualitative (interviews) and quantitative (surveys) research methods which will be mainly based on the data acquired through the findings of the Small Claims Analysis Net (SCAN) project. This project contributes towards examining the ESCP Regulation implementation and efficiency in providing consumers with a legal watershed through using the ODR for their transnational small claims. The outcomes of this research may benefit both academia and policymakers at national and international level.

Keywords: access to justice, consumers, e-commerce, small e-Disputes

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Authors: C. Sridawruang

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Young people today has sexual activities differing from those of earlier generations, in that teenagers are likely to have multiple partners, and are frequently in short-term relationships or with partners that are not well known to them. The proportion of teenage mothers in Thailand has increased. Young people were not specifically addressed during the overall very successful HIV-prevention campaigns. Because of this missed opportunity, they are still unaware of the risk of unsafe sexual behavior. Aims: To describe the reproductive health care services in perspectives of rural Thai teenagers Methods: This survey was one part of a mixed method approach taken using survey and focus groups with 439 teenagers aged 12-18 years in 5 villages, Udon Thani, Thailand. The standard questionnaire survey had been used for collecting data. The numeric data was checked and analyzed by using descriptive statistics. Results: Most teenager respondents stated that they do not know where sexual reproductive health services provided for them. Most teenagers felt difficult to access and talk with health staff about sexual related issues. They stated that discussing, or consulting with health providers might not be safe. Teenagers might lose opportunities to access and get advice from health care services. The mean knowledge score of contraception and condom reproductive was 6.34 from a total score 11. Most teenagers especially girls expressed a need for counseling services and reported a need for telephone services. Conclusions: The need of appropriate information focusing on sexual relationships and contraception should be designed to help young people make wise decisions and there should be set health care services for Thai teenagers to make sure that teenagers could access easily. Health care providers need to be trained to improve their knowledge, attitudes and skills in reproductive health care practices for Thai teenagers.

Keywords: youth friendly health services, rural, Thai, teenagers

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Authors: Carmen J. Savelli, Romy Conzade

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Background: Access to sufficient amounts of safe and nutritious food is a basic human necessity, required to sustain life and promote good health. Food safety and food security are therefore inextricably linked, yet the importance of food safety in this relationship is often overlooked. Methodologies: A literature review and desk study were conducted to examine existing frameworks for discussing food security, especially from an international perspective, to determine the entry points for enhancing considerations for food safety in national and international policies. Major Findings: Food security is commonly understood as the state when all people at all times have physical, social and economic access to sufficient, safe and nutritious food to meet their dietary needs and food preferences for an active and healthy life. Conceptually, food security is built upon four pillars including food availability, access, utilization and stability. Within this framework, the safety of food is often wrongly assumed as a given. However, in places where food supplies are insufficient, coping mechanisms for food insecurity are primarily focused on access to food without considerations for ensuring safety. Under such conditions, hygiene and nutrition are often ignored as people shift to less nutritious diets and consume more potentially unsafe foods, in which chemical, microbiological, zoonotic and other hazards can pose serious, acute and chronic health risks. While food supplies might be safe and nutritious, if consumed in quantities insufficient to support normal growth, health and activity, the result is hunger and famine. Recent estimates indicate that at least 842 million people, or roughly one in eight, still suffer from chronic hunger. Even if people eat enough food that is safe, they will become malnourished if the food does not provide the proper amounts of micronutrients and/or macronutrients to meet daily nutritional requirements, resulting in under- or over-nutrition. Two billion people suffer from one or more micronutrient deficiencies and over half a billion adults are obese. Access to sufficient amounts of nutritious food is not enough. If food is unsafe, whether arising from poor quality supplies or inadequate treatment and preparation, it increases the risk of foodborne infections such as diarrhoea. 70% of diarrhoea episodes occurring annually in children under five are due to biologically contaminated food. Conclusions: An integrated approach is needed where food safety and nutrition are systematically introduced into mainstream food system policies and interventions worldwide in order to achieve health and development goals. A new framework, “Food for Health” is proposed to guide policy development and requires all three aspects of food security to be addressed in balance: sufficiency, nutrition and safety.

Keywords: food safety, food security, nutrition, policy

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Authors: Dominika Collett

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AI applications, such as machine learning, require access to a vast amount of data in the training phase, which can often be the subject of copyright protection. During later usage, the various content with which the application works can be recorded or made available on the basis of which it produces the resulting output. The EU has recently adopted new legislation to secure machine access to protected works under the DSM Directive; but, the issue of machine use of copyright works is not clearly addressed. However, such clarity is needed regarding the increasing importance of AI and its development. Therefore, this paper provides a basic background of the technology used in the development of applications in the field of computer creativity. The second part of the paper then will focus on a legal analysis of machine use of the authors' works from the perspective of existing European and Czech legislation. The main results of the paper discuss the potential collision of existing legislation in regards to machine use of works with special focus on exceptions and limitations. The legal regulation of machine use of copyright work will impact the development of AI technology.

Keywords: copyright, artificial intelligence, legal use, infringement, Czech law, EU law, text and data mining

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Authors: Khaled Sekkoum

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The traditional pharmacopoeia of Algerian Sahara is very rich on vegetable drugs. The great resources and biodiversity of Algerian Sahara flora seem responsible. A survey of medicinal plants used by the local population of the south west of Algeria for the urinary disorders is reported. Sixty-three plant species belonging to thirty-three families were identified. Their botanical and local names, plant part used, mode of use and ailment treated are given.

Keywords: medicinal plants, urinary diseases, Sahara, Algeria

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Authors: Abeer N. Alshukairi, Abdulrahman A. Alrajhi, Abdulfattah W. Alamri, Adel F. Alothman

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We described the nosocomial transmission of a pre-XDR or an MDR case of pulmonary tuberculosis in a HIV negative health care worker in an area endemic for MDR & XDR tuberculosis. With inadequate therapy and non-compliance, his strain developed acquired resistance and he presented with extra-pulmonary XDR tuberculosis in the form of multi-focal osteomyelitis and encysted pleural effusion. He was cured after 2 years of therapy with various anti-tuberculous drugs in addition to interferon gamma.

Keywords: osteomyelitis, treatment, XDR tuberculosis, successful treatment

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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: Maria I. Nuñez-Hernández, Maria L. Riesco

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Background: Exclusive breastfeeding (EBF) up to 6 months old infant have been considered one of the most important factors in the overall development of children. Nevertheless, as resources are scarce, it is essential to identify the most vulnerable groups that have major risk of EBF abandonment, in order to deliver the best strategies. Children of adolescent mothers are within these groups. Aims: To determine the EBF abandonment rate among adolescent mothers and to analyze the associated factors. Methods: Prospective cohort study of adolescent mothers in the southern area of Santiago, Chile, conducted in primary care services of public health system. The cohort was established from 2014 to 2015, with a sample of 105 adolescent mothers and their children at 2 months of life. The inclusion criteria were: adolescent mother from 14 to 19 years old; not twin babies; mother and baby leaving the hospital together after birthchild; correct attachment of the baby to the breast; no difficulty understanding the Spanish language or communicating. Follow-up was performed at 4 and 6 months old infant. Data were collected by interviews, considering EBF as breastfeeding only, without adding other milk, tea, juice, water or other product that not breast milk, except drugs. Data were analyzed by descriptive and inferential statistics, by Kaplan-Meier estimator and Log-Rank test, admitting the probability of occurrence of type I error of 5% (p-value = 0.05). Results: The cumulative EBF abandonment rate at 2, 4 and 6 months was 33.3%, 52.2% and 63.8%, respectively. Factors associated with EBF abandonment were maternal perception of the quality of milk as poor (p < 0.001), maternal perception that the child was not satisfied after breastfeeding (p < 0.001), use of pacifier (p < 0.001), maternal consumption of illicit drugs after delivery (p < 0.001), mother return to school (p = 0.040) and presence of nipple trauma (p = 0.045). Conclusion: EBF abandonment rate was higher in the first 4 months of life and is superior to the population of women who breastfeed. Among the EBF abandonment factors, one of them is related to the adolescent condition, and two are related to the maternal subjective perception.

Keywords: adolescent, breastfeeding, midwifery, nursing

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Authors: Bonguen Onouck Rolande Carole, Ndongo Barthelemy

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The climate change effects on the Lake Chad, coupled with population growth, have pushed large masses of people of various origins towards the lower part of the lower Logonewatershed in search of the benefits of environmental services, causing pressure on the environment and its resources. Economic services are therefore threatened, and the decrease in resources contributes to the deterioration of the social wellbeing resulting to conflicts among/between local communities, immigrants, displaced people, and foreigners. This paper is an information contribution on ethnical conflicts drivers in the area and the provided local management mechanisms such can help mitigate present or future conflicts in similar areas. It also prints out the necessity to alleviate water access deficit and encourage good practices for the population wellbeing. In order to meet the objective, in 2018, through the interface of the World Bank-Cameroon project-PULCI, data were collected on the field directly by discussing with the population and visiting infrastructures, indirectly by a questionnaire survey. Two administrative divisions were chosen (Logoneet Chari, Mayo-Danay) in which targeted localities were Zina, Mazera, Lahai, Andirni near the Waza Park and Yagoua, Tekele, Pouss, respectively. Due to some sociocultural and religious reasons, some information were acquired through the traditional chiefs. A desk study analysis based on resources access and availability conflicts history, and management mechanism was done. As results, roots drivers of ethnical conflicts are struggles over natural resources access, and the possibility of conflicts increases as the scarcity and vulnerabilities persist, creating more sociocultural gaps and tensions. The mitigation mechanisms though fruitful, are limited. There is poor documentation on the topic, the resources management policies of this basin are unsuitable and ineffective for some. Therefore, the restoration of environmental and ecosystems, the mitigation of climate change effects, and food insecurity are the challenges that must be met to alleviate conflicts in these localities.

Keywords: ethnic, communities, conflicts, mitigation mechanisms, natural resources, logone basin

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Authors: Ayanda Magida, Brian Armstrong

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The study aimed to assess the third level of the digital divide among the millennials and post-millennials in South Africa. The millennials are people born from 1981-to 1996, that is, people between the ages of 25-40 years old and post-millennials are people born from 1997 to date. For the study, only post-millennials born between 1997-2003 were included as they were old enough to consent to participation in the study. Data was collected as part of the Ph.D. project that focuses on the relationship between income inequality, the digital divide, and social cohesion in South Africa. The digital divide has three main levels, namely the first, second and third. The first and second focus on access and usage, respectively. The third-level digital divide can be defined as the differences in the benefits associated with being online. The current paper focuses on the third level: the benefits derived by being online using four domains: economic, educational, social, and personal benefits. The economic benefits include income, employment and finance-related activities; the social benefits include socializing belonging, identity, and informal networks. The personal benefits include personal wellbeing and self-actualization. A total of 763 participants completed the survey, and 61.3% were post-millennials between the ages of 18-24 and s 38.6 % were millennials between 25 and 40. The majority of the respondents were female (62%), male (34%) and nonbinary (1%), respectively. Most of the respondents were black, followed by whites, Indians and colored, respectively. Thus, they represented the status of the demographics of the country. Most of the respondents had access to the internet and smartphone. Most expressed that they use laptops (68%) or mobile (71%) to access the internet and 54 % access the internet using wireless/Wi-Fi. There were no differences between the millennial and post-millennial economic and educational benefits of being online. However, the post-millennials were more inclined to use the internet for social and personal benefits than the millennials. This could be attributed to many factors, such as age. The post-millennials are still discovering themselves and therefore would derive social and personal benefits associated with being online. The findings confirm studies that argue that younger generations derive more benefits from being online than the older generation. Based on the findings, it is evident that the post-millennials are not using the internet or online activities for social networks and socializing but can derive economic benefits such as job looking and education benefits from being online. It can be inferred that there are no significant differences between the two groups, and it seems like the third-level digital divide is not evident among the two groups as they both have been able to derive meaningful benefits from being online. Further studies should focus on the third-level divide between the baby boomers and Generation X.

Keywords: third-level digital divide, millennials, post-millennials, online activities

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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: Anika Chebrolu

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Mono-targeted drugs can be of limited efficacy against complex diseases. Recently, multi-target drug design has been approached as a promising tool to fight against these challenging diseases. However, the scope of current computational approaches for multi-target drug design is limited. DeepLig presents a de-novo drug discovery platform that uses reinforcement learning to generate and optimize novel, potent, and multitargeted drug candidates against protein targets. DeepLig’s model consists of two networks in interplay: a generative network and a predictive network. The generative network, a Stack- Augmented Recurrent Neural Network, utilizes a stack memory unit to remember and recognize molecular patterns when generating novel ligands from scratch. The generative network passes each newly created ligand to the predictive network, which then uses multiple Graph Attention Networks simultaneously to forecast the average binding affinity of the generated ligand towards multiple target proteins. With each iteration, given feedback from the predictive network, the generative network learns to optimize itself to create molecules with a higher average binding affinity towards multiple proteins. DeepLig was evaluated based on its ability to generate multi-target ligands against two distinct proteins, multi-target ligands against three distinct proteins, and multi-target ligands against two distinct binding pockets on the same protein. With each test case, DeepLig was able to create a library of valid, synthetically accessible, and novel molecules with optimal and equipotent binding energies. We propose that DeepLig provides an effective approach to design multi-targeted drug therapies that can potentially show higher success rates during in-vitro trials.

Keywords: drug design, multitargeticity, de-novo, reinforcement learning

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Authors: Syed Benazir Firdaus, Debosree Ghosh, Aindrila Chattyopadhyay, Kuladip Jana, Debasish Bandyopadhyay

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Gastro-toxic effect of piroxicam, a classical non-steroidal anti-inflammatory drug (NSAID), has restricted its use in arthritis and similar diseases. The present study aims to find if a combination of melatonin and Murraya koenigii leaf extract therapy can protect against piroxicam induced ulcerative damage in rats. For this study, rats were divided into four groups namely control group where rats were orally administered distilled water, only combination treated group, piroxicam treated group and combination pre-administered piroxicam treated group. Each group of rats consisted of six animals. Melatonin at a dose of 20mg/kg body weight and antioxidant rich Murraya koenigii leaf extract at a dose of 50 mg /kg body weight were successively administered at 30 minutes interval one hour before oral administration of piroxicam at a dose of 30 mg/kg body weight to Wistar rats in the combination pre-administered piroxicam treated group. The rats of the animal group which was only combination treated were administered both the drugs respectively without piroxicam treatment whereas the piroxicam treated animal group was administered only piroxicam at 30mg/kg body weight without any pre-treatment with the combination. Macroscopic examination along with histo-pathological study of gastric tissue using haemotoxylin-eosin staining and alcian blue dye staining showed protection of the gastric mucosa in the combination pre-administered piroxicam treated group. Determination of adherent mucus content biochemically and collagen content through Image J analysis of picro-sirius stained sections of rat gastric tissue also revealed protective effects of the combination in piroxicam mediated toxicity. Gelatinolytic activity of piroxicam was significantly reduced by pre-administration of the drugs which was well exhibited by the gelatin zymography study of the rat gastric tissue. Mean ulcer index determined from macroscopic study of rat stomach reduced to a minimum (0±0.00; Mean ± Standard error of mean and number of animals in the group=6) indicating the absence of ulcer spots on pre-treatment of rats with the combination. Gastro-friendly prostaglandin (PGE2) which otherwise gets depleted on piroxicam treatment was also well protected when the combination was pre-administered in the rats prior to piroxicam treatment. The requirement of the individual drugs in low doses in this combinatorial therapeutic approach will possibly minimize the cost of therapy as well as it will eliminate the possibility of any pro-oxidant side effects on the use of high doses of antioxidants. Beneficial activity of this combination therapy in the rat model raises the possibility that similar protective actions might be also observed if it is adopted by patients consuming NSAIDs like piroxicam. However, the introduction of any such therapeutic approach is subject to future studies in human.

Keywords: gastro-protective action, melatonin, Murraya koenigii leaf extract, piroxicam

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Authors: Abhishek Pandey

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Ibuprofen and Acetaminophen is widely used as prescription & non-prescription medicine. Ibuprofen mainly used in the treatment of mild to moderate pain related to headache, migraine, postoperative condition and in the management of spondylitis, osteoarthritis and rheumatoid arthritis. Acetaminophen is used as an analgesic and antipyretic drug. Ibuprofen having high tendency of sticking to punches of tablet punching machine while Acetaminophen is not ordinarily compressible to tablet formulation because Acetaminophen crystals are very hard and brittle in nature and fracture very easily when compressed producing capping and laminating tablet defects therefore wet granulation method is used to make them compressible. The aim of study was to prepare Ibuprofen and Acetaminophen tablets by direct compression and top spray granulation technique. In this Investigation tablets were prepared by using directly compressible grade excipients. Dibasic calcium phosphate, lactose anhydrous (DCL21), microcrystalline cellulose (Avicel PH 101). In order to obtain best or optimized formulation, nine different formulations were generated among them batch F7, F8, F9 shows good results and within the acceptable limit. Formulation (F7) selected as optimize product on the basis of dissolution study. Furtherly, directly compressible granules of both drugs were prepared by using top spray granulation technique in fluidized bed processor equipment and compressed .In order to obtain best product process optimization was carried out by performing four trials in which various parameters like inlet air temperature, spray rate, peristaltic pump rpm, % LOD, properties of granules, blending time and hardness were optimized. Batch T3 coined as optimized batch on the basis physical & chemical evaluation. Finally formulations prepared by both techniques were compared.

Keywords: direct compression, top spray granulation, process optimization, blending time

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Authors: Garzon V., Bustos R., Salvador J. P., Marco M. P., Pinacho D. G.

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Bacterial resistance to antimicrobial treatment has increased significantly in recent years, making it a public health problem. Large numbers of bacteria are resistant to all or nearly all known antimicrobials, creating the need for the development of new types of antimicrobials or the use of “last line” antimicrobial drug therapies for the treatment of multi-resistant bacteria. Some of the chemical groups of antimicrobials most used for the treatment of infections caused by multiresistant bacteria in the clinic are Glycopeptide (Vancomycin), Polymyxin (Colistin), Lipopeptide (Daptomycin) and Carbapenem (Meropenem). Molecules that require therapeutic drug monitoring (TDM). Due to the above, a methodology based on nanobiotechnology based on an optical and electrochemical biosensor is being developed, which allows the evaluation of the plasmatic levels of some antimicrobials such as glycopeptide, polymyxin, lipopeptide and carbapenem quickly, at a low cost, with a high specificity and sensitivity and that can be implemented in the future in public and private health hospitals. For this, the project was divided into five steps i) Design of specific anti-drug antibodies, produced in rabbits for each of the types of antimicrobials, evaluating the results by means of an immunoassay analysis (ELISA); ii) quantification by means of an electrochemical biosensor that allows quantification with high sensitivity and selectivity of the reference antimicrobials; iii) Comparison of antimicrobial quantification with an optical type biosensor; iv) Validation of the methodologies used with biosensor by means of an immunoassay. Finding as a result that it is possible to quantify antibiotics by means of the optical and electrochemical biosensor at concentrations on average of 1,000ng/mL, the antibodies being sensitive and specific for each of the antibiotic molecules, results that were compared with immunoassays and HPLC chromatography. Thus, contributing to the safe use of these drugs commonly used in clinical practice and new antimicrobial drugs.

Keywords: antibiotics, electrochemical biosensor, optical biosensor, therapeutic drug monitoring

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Authors: Hemalatha Rallapalli, K. Lal Kishore

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In comparison to systems that are typically designed to provide capabilities over a narrow frequency range through hardware elements, the next generation cognitive radios are intended to implement a broader range of capabilities through efficient spectrum exploitation. This offers the user the promise of greater flexibility, seamless roaming possible on different networks, countries, frequencies, etc. It requires true paradigm shift i.e., liberalization over a wide band of spectrum as well as a growth path to more and greater capability. This work contributes towards the design and implementation of an open spectrum access (OSA) feature to unlicensed users thus offering a frequency agile radio platform that is capable of performing spectrum sensing over a wideband. Thus, an ultra-wideband (UWB) radio, which has the intelligence of spectrum sensing only, unlike the cognitive radio with complete intelligence, is named as a Smart Software Radio (SSR). The spectrum sensing mechanism is implemented based on energy detection. Simulation results show the accuracy and validity of this method.

Keywords: cognitive radio, energy detection, software radio, spectrum sensing

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Authors: Oljana Hoxhaj

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The integration process of Albania into the European family carries many difficulties. In this context, the Albanian legislator is inclined to implement in the domestic legal framework models which have been successful in other countries. Our paper aims to present an analytical and comparative approach to the health system in Albania and France, mainly focusing on citizen’s access to these services. Different standards and cultures between states, in the context of an approximate model, will be the first challenge of our paper. Over the last few years, the Albanian government has undertaken concrete reforms in this sector, aiming to transform the vision on which the previous health system was structured. In this perspective, the state fulfills not only an obligation to its citizens, but also consolidates progressive steps toward alignment with European Union standards. The necessity to undertake a genuine reform in this area has come as an exigency of society, which has permanently identified problems within this sector, considering it ineffective, out of standards, and corrupt. The inclusion of health services on the Albanian government agenda reflects its will in the function of good governance, transparency, and broadening access to the provision of quality health services in the public and private sectors. The success of any initiative in the health system consists of giving priority to patient needs. Another objective that should be in the state's consideration is to create the premise to provide a comprehensive process on whose foundations partnership and broader co-operation with beneficiary entities are established in any decision-making that is directly related to their interests. Some other important and widespread impacts on the effective realization of citizens' access to the healthcare system coincide with the construction of appropriate infrastructure, increasing the professionalism and qualification of medical staff, and the allocation of a higher budget. France has one of the most effective healthcare models in Europe. That is why we have chosen to analyze this country, aiming to highlight the advantages of this system, as well as the commitment of the French state to drafting effective health policies. In the framework of the process of harmonization of the Albanian legislation with that of the European Union, through our work, we aim to identify the space to implement the whole of these legislative innovations in the Albanian legislation.

Keywords: effective service, harmonization level, innovation, reform

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Authors: Rajendra Jangde, Deependra Singh

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Present work was based with objective to release of the antimicrobial and debriding agent in sustained manner at the wound surface. In order to provide a long-lasting antimicrobial action and moist environment on wound space, Biocompatible moist system was developed for complete healing. In the present study, a biocompatible moist system of PVA-gelatin hydrogel was developed capable of carrying multiple drugs- Quercetin and Cabopol in controlled manner for effective and complete wound healing. Carbopol and Quercetin were prepared by thin film hydration techniques and optimized system was incorporated in PVA-Gelatin slurry. PVA-Gelatin hydrogels were prepared by freeze thaw method. The prepared dispersion was casted into films to prepare multiphase hydrogel system and characterized by in vitro and in vivo studies. Results revealed the uniform dispersion of microspheres in a three-dimensional matrix of the PVA-Gelatin hydrogel observed at different magnifications. The in vitro release data showed typical biphasic release pattern, i.e., a burst release followed by a slower sustained release for 5 days. Prepared system was found to be stable under both normal and accelerated conditions. Histopathological study showed significant (p<0.05) increase in fibroblast cells, collagen fibres and blood vessels formation. All parameters such as wound contraction, tensile strength, histopathological and biochemical parameters- hydroxyproline content, protein level, etc. were observed significant (p<0.05) in comparison to control group. Present results suggest an accelerated re-epithelialization under moist wound environment with delivery of multiple drugs effective at different stages of wound healing cascade with minimum disturbance of wound bed.

Keywords: multiphase hydrogel, optimization quercetin, wound healing

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Authors: S. I. Mwasha, Z. Robinson, M. Musgrave

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Communities, especially in the global south, have been reported to have low adaptive capacity to cope with climate change impacts. As an attempt to improve adaptive capacity, most studies have focused on understanding the access of the household resources which can contribute to resilience against changes. However, little attention has been shown in uncovering how the household resources could be used and their implications to resilience against weather related shocks. By using a case study qualitative study, this project analyzed the trends in livelihoods practices and their implication to social equity. The study was done in three different villages within Kilimanjaro region. Each in different agro ecological zone. Two focus group discussions in two agro-ecological zones were done, one for women and another one for men except in the third zone where focus group participant were combined together (due to unforeseen circumstances). In the focus group discussion, several participatory rural appraisal tools were used to understand trend in crops and animal production and the use in which it is made: climate trends, soil fertility, trees and other livelihoods resources. Data were analyzed using thematic network analysis. Using an amalgam of magnitude (to note weather comments made were positive or negative) and descriptive coding (to note the topic), six basic themes were identified under social equity: individual ownership, family ownership, love and respect, women no education, women access to education as well as women access to loans. The results implied that despite mum and dad in the family providing labor in the agro pastoral activities, there were separations on who own what, as well as individual obligations in the family. Dad owned mostly income creating crops and mum, food crops. therefore, men controlled the economy which made some of them become arrogant and spend money to meet their interests sometimes not taking care of the family. Separation in ownership was reported to contribute to conflicts in the household as well as causing controversy on the use income is spent. Men were reported to use income to promote matriarchy system. However, as women were capacitated through access to education and loans they become closer to their husband and get access to own and plan the income together for the interest of the family. Joint ownership and planning on the household resources were reported to be important if families have to better adapt to climate change. The aim of this study is not to show women empowerment and joint ownership and planning as only remedy for low adaptive capacity. There is the need to understand other practices that either directly or indirectly impacts environmental integrity, food security and economic development for household resilience against changing climate.

Keywords: adaptive capacity, climate change, resilience, women empowerment

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Authors: Mesfin Nigussie

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The objectives of the study were to identify factors affecting rural households’ willingness to install biogas plant and amount willingness to pay in order to examine determinants of effective demand for biogas technology. A multistage sampling technique was employed to select 120 respondents for the study. The binary probit regression model was employed to identify factors affecting rural households’ decision to install biogas technology. The probit model result revealed that household size, total household income, access to extension services related to biogas, access to credit service, proximity to water sources, perception of households about the quality of biogas, perception index about attributes of biogas, perception of households about installation cost of biogas and availability of energy source were statistically significant in determining household’s decision to install biogas. Tobit model was employed to examine determinants of rural household’s amount of willingness to pay. Based on the model result, age of the household head, total annual income of the household, access to extension service and availability of other energy source were significant variables that influence willingness to pay. Providing due considerations for extension services, availability of credit or subsidy, improving the quality of biogas technology design and minimizing cost of installation by using locally available materials are the main suggestions of this research that help to create effective demand for biogas technology.

Keywords: biogas technology, effective demand, probit model, tobit model, willingnes to pay

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Authors: Chukwudalu C. Nwazojie, Wole W. Soboyejo, John Obayemi, Ali Salifu Azeko, Sandra M. Jusu, Chinyerem M. Onyekanne

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The conventional methods for the diagnosis and treatment of breast cancer include bulk systematic mammography, ultrasound, dynamic contrast-enhanced fast 3D gradient-echo (GRE) magnetic resonance imaging (MRI), surgery, chemotherapy, and radiotherapy. However, nanoparticles and drug-loaded polymer microspheres for disease (cancer) targeting and treatment have enormous potential to enhance the approaches that are used today. The goal is to produce an implantable biomedical device for localized breast cancer drug delivery within Africa and the world. The main advantage of localized delivery is that it reduces the amount of drug that is needed to have a therapeutic effect. Polymer blends of poly (D,L-lactide-co-glycolide) (PLGA) and polycaprolactone (PCL), which are biodegradable, is used as a drug excipient. This work focuses on the development of PLGA-PCL (poly (D,L-lactide-co-glycolide) (PLGA) blended with based injectable drug microspheres and are loaded with anticancer drugs (prodigiosin (PG), and paclitaxel (PTX) control) and also the conjugated forms of the drug functionalized with LHRH (luteinizing hormone-releasing hormone) (PG-LHRH, and PTX- LHRH control), using a single-emulsion solvent evaporation technique. The encapsulation was done in the presence of PLGA-PCL (as a polymer matrix) and poly-(vinyl alcohol) (PVA) (as an emulsifier). Comparative study of the various drugs release kinetics and degradation mechanisms of the PLGA-PCL with an encapsulated drug is achieved, and the implication of this study is for the potential application of prodigiosin PLGA-PCL loaded microparticles for controlled delivery of cancer drug and treatment to prevent the regrowth or locoregional recurrence, following surgical resection of triple-negative breast tumor.

Keywords: cancer, polymers, drug kinetics, nanoparticles

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Authors: Esha Thakkar, Ina Liu, Kalynn Hosea, Shana Katz, Katie Marks, Sarah Hall, Cat Liu, Suzanne Harris

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Purpose: Inequities in mental healthcare accessibility are cited as an international public health concern by the World Health Organization (WHO) and National Alliance on Mental Illness (NAMI). These disparities are further exacerbated in racial and ethnic minority groups and are especially concerning in health professional training settings such as Doctor of Pharmacy (PharmD) programs and postgraduate residency training where mental illness rates are high. The purpose of the study was to determine baseline access to culturally sensitive mental healthcare and how to improve such access and communication for racially and ethnically minoritized pharmacy students and residents at one school of pharmacy and a partnering academic medical center in the United States. Methods: This IRB-exempt study included 60-minute focus groups conducted in person or online from November 2021 to February 2022. Eligible participants included PharmD students in their first (P1), second (P2), third (P3), or fourth year (P4) or pharmacy residents completing a postgraduate year 1 (PGY1) or PGY2 who identify as Black, Indigenous, or Person of Color (BIPOC). There were four core theme questions asked during the focus groups to lead the discussion, specifically on the core themes of personal barriers, identities, areas that are working well, and areas for improvement. Participant responses were transcribed and analyzed using an open coding system with two individual reviews, followed by collaborative and intentional discussion and, as needed, an external audit of the coding by a third research team member to reach a consensus on themes. Results: This study enrolled 26 participants, with eight P1, five P2, seven P3, two P4, and four resident participants. Within the four core themes of barriers, identities, areas working well, and areas for improvement, emerging subthemes included: lack of time, access to resources, and stigma under barriers; lack of representation, cultural and family stigma, and gender identities for identity barriers; supportive faculty, sense of community and culture supporting paid time off for areas going well; and wellness days, reduced workload and diversity of the workforce in areas of improvement. Subthemes sometimes varied within a core theme depending on the participant year. Conclusions: There is a gap in the literature in addressing barriers and disparities in mental health access for pharmacy trainees who identify as BIPOC. We identified key findings in regards to barriers, identities, areas going well and areas for improvement that can inform the School and the Residency Program in two priority initiatives of well-being and diversity equity and inclusion in creating actionable recommendations for trainees, program directors, and employers of our institutions, and also has the potential to provide insight for other organizations about the structures influencing access to culturally sensitive care in BIPOC trainees. These findings can inform organizations on how to continue building on communication with those who identify as BIPOC and improve access to care.

Keywords: mental health, disparities, minorities, wellbeing, identity, communication, barriers

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Authors: Kubra Akbayrak

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In parallel with increasing inclusive practice for pupils with vision impairments, the role of specialist teachers who have specialized in the area of vision impairment has dramatically changed in recent years. This study, therefore, aims to provide a holistic perspective towards the distinctive role of specialist teachers of pupils with vision impairments in different educational settings (including mainstream settings, special school settings, etc.) in Turkey and England. Within the scope of the study, semi-structured interviews have been conducted with 17 specialist teachers in Turkey and 14 specialist teachers in England in order to reveal the perception of specialist teachers regarding their roles in different educational settings as well as their perception towards their pre-service training. As this study is a part of an ongoing PhD research, the qualitative data through semi-structured interviews will be analyzed through using Bronfenbrenner’s ecological systems theory as a theoretical framework in order to provide a holistic view regarding the role of specialist teachers particularly in facilitating curriculum access for pupils with vision impairments in England and Turkey. However, the initial findings broadly illustrate that specialist teachers who work in special school settings have different understanding regarding their roles compared to specialist teachers who work in mainstream settings in relation to promoting independence for pupils with vision impairments. The initial findings also imply that specialist teachers in England and Turkey have different perception about their roles in relation to providing specialist advice and guidance for families of pupils. With the completion of the analysis of the study, it is hoped that the findings will provide an insight into the role of specialist teachers in order to provide implication for programmes which prepare specialist teachers of pupils with vision impairments.

Keywords: curriculum access, pupils with vision impairments, specialist teachers, special education

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Authors: Zaman Jawahar, Anne Rouve-Khiev, Elizabeth Hoban, Joanne Williams

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Ensuring access to timely obstetric care is essential to prevent maternal deaths. Geographical barriers pose significant challenges for women accessing quality reproductive and maternal health services in rural Cambodia. This policy brief affirms the need to address the issue of transportation and cost (direct and indirect) as critical barriers to accessing reproductive and maternal health (RMH) services in four provinces in Northeast Cambodia (Kratie, Ratanak Kiri, Mondul Kiri, Stung Treng). A systemic search of the literature identified 1,116 articles, and only ten articles from low-and-middle-income countries met the inclusion criteria. The ten articles reported on transportation and cost related to accessing RMH services. In addition, research findings from Partnering to Save Lives (PSL) studies in the four provinces were included in the analysis. Thematic data analysis using the information in the ten articles and PSL research findings was conducted, and the findings are presented in this paper. The key findings are the critical barriers to accessing RMH services in the four provinces because women experience: 1) difficulties finding affordable transportation; 2) lack of available and accessible transportation; 3) greater distance and traveling time to services; 4) poor geographical terrain and; 5) higher opportunity costs. Distance and poverty pose a double burden for the women accessing RMH services making a facility-based delivery less feasible compared to home delivery. Furthermore, indirect and hidden costs associated with institutional delivery may have an impact on women’s decision to seek RMH care. Existing health financing schemes in Cambodia such as the Health Equity Fund (HEF) and the Voucher Scheme contributed to the solution but have also shown some limitations. These schemes contribute to improving access to RMH services for the poorest group, but the barrier of transportation costs remains. In conclusion, initiatives that are proven to be effective in the Cambodian context should continue or be expanded in conjunction with the HEF, and special consideration should be given to communities living in geographically remote regions and difficult to access areas. The following strategies are recommended: 1) maintain and further strengthen transportation support in the HEF scheme; 2) expand community-based initiatives such as Community Managed Health Equity Funds and Village Saving Loans Associations; 3) establish maternity waiting homes; and 4) include antenatal and postnatal care in the provision of integrated outreach services. This policy brief can be used to inform key policymakers and provide evidence that can assist them to develop strategies to increase poor women’s access to RMH services in low-income settings, taking into consideration the geographic distance and other indirect costs associated with a facility-based delivery.

Keywords: access, barriers, northeast Cambodia, reproductive and maternal health service, transportation and cost

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Authors: Lawan Ja’afar Tahir

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This research work centered on the problem of free Arms flow around the Nigeria and Chad Border. The whole of the northeastern Nigerian region has been devastated by the crisis of insecurity facilitated by more than a decade of insurgency. One of the major issues of concern to security experts and personnel in the country is how the insurgents are getting access to weapons, which gave them more strength to fight the war for this long period, which has become so difficult to overcome. Among the possible avenues that continue to strengthen the enemies is the easy access to the arms flow from the neighboring countries, especially the Republic of Chad, which borders Nigeria to the east, where Boko Haram gained firm roots. This paper, therefore, looked at the nature of the waterway of the Nigeria/Chad Border, which has become a source of strength to the insurgents as the flow of weapons is one of the cheapest things on the Border. The availability of such arms flow has also led to the People abandoning their lands and economic and commercial activities, especially those settlements between the Border of these two countries. For more than eight years now, they have suspended their livelihood activities, roads were blocked and chances of survival in the rural areas were minimal due to the frequent attacks carried out by the insurgents. However, this research looks at the causes of the arms flow along the Border of these neighboring countries, the extent of damage done as a result of the availability of the weapons, and how far the Nigerian government has gone in curtailing the menace of the flow of dangerous weapons into the country. The research looked at the ways arm dealers are conniving with settlers along the border as well as the various ways they followed to reach their target. The work provided suggestion as to how the fragile Border should be managed with the view to reduce the influx of arms without control, which, according to this research, is the central factor that continues to unleash and give terror groups the opportunity to destroy people for more than a decade.

Keywords: border, insecurity, weapons, management

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