Search results for: drug accessibility

Authors: Konstantinos Tolidis

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The mountains are amongst the most fragile environments in the world. The world’s mountain areas cover 24% of the Earth’s land surface and are home to 12% of the global population. A further 14% of the global population is estimated to live in the vicinity of their surrounding areas. As urbanization continues to increase in the world, the mountains are also key centers for recreation and tourism; their attraction is often heightened by their remarkably high levels of biodiversity. Due to the fact that the features in mountain areas vary spatially (development degree, human geography, socio-economic reality, relations of dependency and interaction with other areas-regions), the spatial planning on these areas consists of a crucial process for preserving the natural, cultural and human environment and consists of one of the major processes of an integrated spatial policy. This research has been focused on the spatial decision problem of land use allocation optimization which is an ordinary planning problem on the mountain areas. It is a matter of fact that such decisions must be made not only on what to do, how much to do, but also on where to do, adding a whole extra class of decision variables to the problem when combined with the consideration of spatial optimization. The utility of optimization as a normative tool for spatial problem is widely recognized. However, it is very difficult for planners to quantify the weights of the objectives especially when these are related to mountain areas. Furthermore, the land use allocation optimization problems at mountain areas must be addressed not only by taking into account the general development objectives but also the spatial objectives (e.g. compactness, compatibility and accessibility, etc). Therefore, the main research’s objective was to approach the land use allocation problem by utilizing a hybrid meta-heuristic optimization technique tailored to the mountain areas’ spatial characteristics. The results indicates that the proposed methodological approach is very promising and useful for both generating land use alternatives for further consideration in land use allocation decision-making and supporting spatial management plans at mountain areas.

Keywords: multiobjective land use allocation, mountain areas, spatial planning, spatial decision making, meta-heuristic methods

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Authors: Jennifer Isabelle Rios Rendón, Ursula Sanchez, Dana Lee Baker

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Disability Policy in México has witnessed numerous changed throughout the years. Physical disabilities are more often recognized in Mexican culture. However, with an emerging focus on neurological disabilities or differences in individuals’ new policies are needed to serve better and understand the needs of these populations. The need to understand and communicate with local leaders is imperative, as the lens used to analyze autism has historically been from a Western school of thought. We are looking to comprehend the disability policy subsystem in México - specifically how autism is perceived, the language used to describe it, and how it ties to the cultural stigma of disabilities that exist in México. Therefore, to understand this, we seek to interview multiple policy leaders on their experience in autism and disability policy. The goal is to conduct qualitative research through interviews with local autism and disability leaders in México. This methodology aims to answer the questions of what language commonly and culturally is utilized in disability policy, the context of how autism is perceived in México, and in general, the lived experience of the disability policy leaders that take part in this effort in México. Local activists and policy leaders were initially found through an online search then collected using snowball sampling. The interviews were conducted through a series of pre-formulated questions that the policy leader answered via email or a phone conversation with the researchers. Acknowledging the importance of language and accessibility, the need for the content to be in both English and Spanish as well as auditory and visual is essential to take steps in the inclusion of a Neurodiverse group of leaders. This work is a demonstration of the framework of the investigation which hopes to create a more complete understanding of the policy and political culture around autism in México. Results of the project include new insight into the developing relationship between the President Andrés Manuel López Obrador’s administration, disability activists, and neurodiverse communities. The project contributes to denormalizing the legacy of white supremacy in autism related, historically rooted in the assumption that autism occurs predominantly in white communities.

Keywords: autism, disability leaders, disability policy, México, Neurodiversity

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Authors: Daniel C. Bonzo

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Practical considerations lead to the use of unit of analysis within subjects, e.g., bleeding episodes or treatment-related adverse events, in rare disease settings. This is coupled with data augmentation techniques such as extrapolation to enlarge the subject base. In general, one can think about extrapolation of data as extending information and conclusions from one estimand to another estimand. This approach induces hierarchichal clustered data with varying cluster sizes. Extrapolation of clinical trial data is being accepted increasingly by regulatory agencies as a means of generating data in diverse situations during drug development process. Under certain circumstances, data can be extrapolated to a different population, a different but related indication, and different but similar product. We consider here the problem of estimation (point and interval) using a mixed-models approach under an extrapolation. It is proposed that estimators (point and interval) be constructed using weighting schemes for the clusters, e.g., equally weighted and with weights proportional to cluster size. Simulated data generated under varying scenarios are then used to evaluate the performance of this approach. In conclusion, the evaluation result showed that the approach is a useful means for improving statistical inference in rare disease settings and thus aids not only signal detection but risk-benefit evaluation as well.

Keywords: clustered data, estimand, extrapolation, mixed model

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Authors: Rani Fernandez

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As global concerns regarding environmental degradation and climate change intensify, the imperative for sustainable living has never been more critical. This research delves into the role of eco-products in everyday life as a pivotal strategy for achieving sustainability. The study investigates the awareness, adoption, and impact of eco-friendly products on individual and community levels. The research employs a mixed-methods approach, combining surveys, interviews, and case studies to explore consumer perceptions, behaviours, and motivations surrounding the use of eco-products. Additionally, life cycle assessments are conducted to evaluate the environmental footprint of selected eco-products, shedding light on their tangible contributions to sustainability. The findings reveal the diverse range of eco-products available in the market, from biodegradable packaging to energy-efficient appliances, and the extent to which consumers integrate these products into their daily routines. Moreover, the research examines the challenges and opportunities associated with widespread adoption, considering factors such as cost, accessibility, and efficacy. In addition to individual consumption patterns, the study investigates the broader societal impact of eco-product integration. It explores the potential for eco-products to drive systemic change by influencing supply chains, corporate practices, and government policies. The research highlights successful case studies of communities or businesses that have effectively incorporated eco-products, providing valuable insights into scalable models for sustainability. Ultimately, this research contributes to the discourse on sustainable living by elucidating the pivotal role of eco-products in shaping environmentally conscious behaviours. By understanding the dynamics of eco-product adoption, policymakers, businesses, and individuals can collaboratively work towards a more sustainable future. The implications of this study extend beyond academia, informing practical strategies for fostering a global shift towards sustainable consumption and production.

Keywords: eco-friendly, sustainablity, environment, climate change

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Authors: J. Cadby, K. Miyazawa

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Information and Communication Technology (ICT) has been widely adopted into the agricultural landscape with advancements of mobile connectivity and data accessibility. In developed nations, mobile-technology is well integrated into marketing transactions, and also plays a crucial role in making data-driven decisions on-farm. In developing nations, mobile banking and access to agricultural extension services allow for informed decision-making and smoother transactions. In addition, the availability of updated and readily available market and climate data provides a negotiation platform, reducing economic risks for farmers worldwide. The total usage of mobile technology has risen over the past 20 years, and almost three-quarters of the world’s population subscribes to mobile technology. This study reviewed mobile technology integration into agricultural systems in developing and developed nations. Data from secondary sources were collected and investigated. The objectives of the study include a review of the success of mobile banking transactions in developing nations, and a review of application and SMS based services for direct marketing in both developed and developing nations. Rural farmers in developing countries with access to diverse m-banking options experienced increased access to farm investment resources with the use of mobile banking technology. Rural farmers involved in perishable crop production were also more likely to benefit from mobile platform sales participation. ICT programs reached through mobile application and SMS increased access to agricultural extension materials and marketing tools for demographics that faced literacy-challenges and isolated markets. As mobile technology becomes more ubiquitous in the global agricultural system, training and market opportunities to facilitate mobile usage in developing agricultural systems are necessary. Digital skills training programs are necessary in order to improve equal global adoption of ICT in agriculture.

Keywords: market participation, mobile banking, mobile technology, rural farming

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Authors: Hae Dun Kim, Joo Hyun Jang, Geu Rim Seo, Kyung Soo Ra, Hyung Joo Suh

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Lactuca sativa (lettuce) has been known for its medical property to relieve anxiety and nervous. This study was implemented to investigate sleep-promoting effects of the lettuce alcohol extract (LAE). Caffeine is widely used psychoactive substance known to induced wakefulness and insomnia to its consumers. In the present study, the sedative-hypnotic activity of the LAE was studied using the method of pentobarbital-induced sleep in the mouse model. The LAE was administrated to mice 30 min before the pentobarbital injection. The LAE prolonged the pentobarbital-induced sleep duration and decreased sleep latency. The effects of LAE were comparable to those of induced by diazepam. Another study was performed to examine whether LAE ameliorates caffeine-induced sleep disturbance in mice. Additionally, caffeine (10 mg/kg, p.o) delayed sleep onset and reduced sleep duration of mice. Conversely, LAE treatment (80 or 160 mg/kg, p.o), especially at 160 mg/kg, normalized the sleep disturbance induced by caffeine. LAE supplementation can counter the sleep disturbance induced by caffeine. These results suggest that LAE possess significant sedative-hypnotic activity, which supports the popular use of lettuce for treatment of insomnia and provide the basis for new drug discovery. Furthermore, these results demonstrate that the lettuce extract may be preferable for the treatment of insomnia.

Keywords: caffeine, Lactuca sativa, sleep duration, sleep latency

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Authors: M. Krishna

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The study was intended to identify if scalp cooling therapy is effective on preventing chemotherapy-induced hair loss among cancer patients. Critical literature of non-randomized controlled trials was used to investigate whether scalp cooling therapy is effective on preventing chemotherapy-induced alopecia. The review identified that scalp cooling therapy is effective on preventing chemotherapy-induced alopecia. Most of the patients receiving chemotherapy experience alopecia. It is also perceived as the worst effect of chemotherapy. This may be severe and lead the patients to withdraw the chemo treatment. The image disturbance caused by alopecia will make the patient depressed and will lead to declined immunity. With the knowledge on effectiveness of scalp cooling therapy on preventing chemotherapy-induced alopecia, patient undergoing chemotherapy will not be hesitant to undergo the treatment. Patients are recommended to go through scalp cooling therapy every chemo cycle and the proper therapy duration is 30 minutes before, during chemo. The suggested duration of the scalp cooling therapy is 45-90 minutes for an effective and positive outcome. This finding is excluding other factors of alopecia such as menopause, therapeutic drugs, poor hair density, liver function problems, and drug regimes.

Keywords: alopecia, cancer, chemotherapy, scalp cooling therapy

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Authors: Mir Hussain Nawaz, Lyudmila Nedyalkova, Haizhong Zhu, Wael M. Rabeh

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In this study, we aim to biochemically and structurally characterize the interactions of human HK2 with the mitochondria in addition to the role of its N-terminal domain in catalysis and stability of the full-length enzyme. Here, we solved the crystal structure of human HK2 in complex with glucose and glucose-6-phosphate (PDB code: 2NZT), where it is a homodimer with catalytically active N- and C-terminal domains linked by a seven-turn α-helix. Different from the inactive N-terminal domains of isozymes 1 and 3, the N- domain of HK2 not only capable to catalyze a reaction but it is responsible for the thermodynamic stabilizes of the full-length enzyme. Deletion of first α-helix of the N-domain that binds to the mitochondria altered the stability and catalytic activity of the full-length HK2. In addition, we found the linker helix between the N- and C-terminal domains to play an important role in controlling the catalytic activity of the N-terminal domain. HK2 is a major step in the regulation of glucose metabolism in cancer making it an ideal target for the development of new anticancer therapeutics. Characterizing the structural and molecular mechanisms of human HK2 and its role in cancer metabolism will accelerate the design and development of new cancer therapeutics that are safe and cancer specific.

Keywords: cancer metabolism, enzymology, drug discovery, protein stability

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Authors: Watchawin Ekphinitphithaya, Patompong Satapornpong

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Introduction: Carbamazepine (CBZ) is one of the most prescribed antiepileptic drugs (AEDs) by neurologists and non-neurologist worldwide. CBZ is usually prescribed along with other drugs, leading to the possibility of severe cutaneous adverse drug reactions (SCARs). The HLA-B*15:02 is strongly associated with CBZ-induced Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS–TEN) in the Han Chinese and other Asian populations but not in European populations, while HLA-A*31:01 allele has been reported to be associated with CBZ-induced SCARs in European population and Japanese. Objective: The aim of this study is to investigate the distribution of pharmacogenetics HLA-A*31:01 marker in a healthy Thai population associated with Carbamazepine-induced SCARs. Materials and Methods: Prospective study, 350 unrelated healthy Thais were recruited in this study. Human leukocyte antigen-A alleles were genotyped using PCR-sequence specific oligonucleotides (PCR-SSOs). Results: The frequency of HLA-A alleles were HLA-A*11:01 (190 alleles, 27.14%), HLA-A*24:02 (82 alleles, 11.71%), HLA-A*02:03 (80 alleles, 11.43%), HLA-A*33:03 (76 alleles, 10.86%), HLA-A*02:07 (58 alleles, 8.29%), HLA-A*02:01 (35 alleles, 5.00%), HLA-A*24:07 (29 alleles, 4.14%), HLA-A*02:06 – HLA-A*30:01 (15 alleles, 2.14%), and HLA-A*01:01 (14 alleles, 2.00%). Particularly, the number of HLA-A*31:01 alleles was 6 of 700 (0.86%) in the healthy Thai population. Many research presented varying distributions of HLA-A*31:01 in Asians, including 2% of Han Chinese, 9% of Japanese and 5% of Koreans. In addition, this allele was found approximately 2-5% in the Caucasian population. Conclusions: Thus, the pharmacogenetics database is vital to support in many populations, especially in Thais, for screening HLA-A*31:01 allele to avoid CBZ-induced SCARs before initiating treatments in each population.

Keywords: Carbamazepine, HLA-A*31:01, Thai population, pharmacogenetics

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Authors: Morteza Naderi

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The Persian fallow deer was considered as a globally extinct species until 1956 when a small population was rediscovered from Dez Wildlife Refuge and Karkheh Wildlife Refuge in southwestern parts of Iran. After long species rehabilitation process, the species was transplanted to Dasht-e-Naz Wildlife Refuge in northern Iran, and from where, follow deer was introduced to the different selected habitats such as Ashk Island in Lake Uromiyeh National Park. During 12 years, (from 1978 to 1989) 58 individuals (25 males and 33 females) were transferred to Ask Island. The main threat to the established population was related to the freshwater shortage and existing just one single trough such as high mortality rate of adult males during rutting season, snake biting and dilutional hyponatremia. Desiccation of Lake Uromiyeh in recent years raised new challenges to the conservation process, as about 80 individuals, nearly one third of the population were died in 2011. Connection of Island to the mainland caused predators’ accessibility (such as wolf and Jackal) to the Ask Island and higher mortality because of follow deer attraction to the surrounding mainland farms. Conservation team faced such new challenges that may cause introduction plan to be probably failed. Investigations about habitat affinities and carrying capacity are the main basic researches in the management and conservation of the species. Logistic regression analysis showed that the presence of the different fresh water resources as well as Allium akaka and Pistacia atlantica are the main environmental variables affect Follow deer habitat selection. Habitat carrying capacity analysis both in summer and winter seasons indicated that Ashk Island can support 240±30 of Persian follow deer.

Keywords: carrying capacity, follow deer, lake Uromiyeh, microhabitat affinities, population oscillation, predation, sex ratio

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Authors: Mochammad Indra Permana, Andhiani Sharfina Arnellya, Dika Pramita Destiani, Budhi Prihartanto

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Cardiovascular disease is the cause of the highest mortality rates in the world. The number of cardiovascular disease patients is increasing every year. Data obtained from World Health Organization (WHO) that 17,5 million people died from this disease. The condition of cardiovascular diseases such as atrial fibrillation, myocardial infarction, venous thromboembolism, and several other conditions need anticoagulant therapy. Results of the anticoagulant therapy are measured not only by the effectiveness of International Normalized Ratio (INR) value but also by the quality of life of the patients. The purpose of this study was to determine the quality of life of patients on oral anticoagulant therapy in outpatient cardiac department Dr. Hasan Sadikin central general hospital, Bandung, Indonesia. This is a cross-sectional study with collecting data from the quality of life questionnaire and medical record of the patients. The results of this study showed that 28 patients (46,7%) had a good quality of life, 30 patients (50%) had a moderate quality of life, and 2 patients (3,3%) had a poor quality of life with no significant differences in quality of life based on age, gender, diagnosis, and duration of drug use.

Keywords: anticoagulant, cardiovascular diseases, INR, quality of life

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Authors: Mohammed Sani Abdulai

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Public sector budgeting, all over the world, is underpinned by some universally accepted principles of sound budget management such as budget unity, universality, annuality, and a balanced budget. These traditional principles, though fundamental, had, in recent years, been augmented by the more modern principles of budgeting within fiscal objective, alignment with medium-term strategic plans as well as the observance of such related concepts as transparency, openness and accessibility. In this paper, we have endeavored to shed light, from literature and practice, on the meaning and purposes of such fundamental budgeting principles. We have also assessed the extent to which the Government of Ghana’s budget complies with the four traditional principles of budget unity, universality, annuality, and a balanced budget and the three out of the ten modern principles of budgetary governance of Organisation for Economic Co-operation and Development (OECD). We did so by using a qualitative method of review and analysis of existing documents and the performance assessment reports on Ghana’s Public Financial Management (PFM) measured using such frameworks as the Public Expenditure and Financial Accountability (PEFA), the Open Budget Survey (OBS) and its Index (OBI), the reports and action plans of Open Government Partnership (OGP) and the Global Initiative for Fiscal Transparency (GIFT). Other performance assessment reports that were relied on included, but not limited to, the Joint Evaluation Report of PFM in Ghana, 2001-2010, and the Joint Evaluation of Budget Support to Ghana, 2005-2015. We have, through this paper, brought to the fore the lessons that could be learned on how those budgetary principles undergird the Government of Ghana’s budget formulation, execution, accounting, control, and oversight. These lessons include, but are not limited to, the need for both scholars and practitioners in the PFM space to be aware of the impact of those principles on public sector budgeting.

Keywords: annulaity, balanced budget, budget unity, budgetary principles, OECD’s principles on budgetary governance, open budget index, public expenditure and financial accountability, universality

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Authors: Samah Lakehal, A. Meliani, F. Z. Benrebiha, C. Chaouia

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In the last few years, due to the misuse of antibiotics and an increasing incidence of immunodeficiency-related diseases, the development of microbial drug resistance has become more and more of a pressing problem. Recently, natural products from medicinal plants represent a fertile ground for the development of novel antibacterial agents. Plants essential oils have come more into the focus of phytomedicine. The present study describes antimicrobial activity of Rosmarinus officinalis L. essential oil known medicinally for its powerful antibacterial properties. The essential oil of rosemary obtained by hydrodistillation (using Clevenger type apparatus) growing in Algeria (Djelfa city of south Algeria) was investigated by GC-MS. The essential oil yield of the study was 1.4 %. The major components were found to be camphor, camphene, 1,8-cineole. The essential oil has been tested for antimicrobial activity against eight bacteria (Gram-negative and Gram-positive), and three fungi including Candida albicans. Inhibition of growth was tested by the agar diffusion method based on the determination of the diameter of inhibition. The oil was found to have significant antibacterial activity and therefore can be used as a natural antimicrobial agent for the treatment of several infectious diseases caused by those germs, which have developed resistance to antibiotics.

Keywords: antimicrobial activity, Rosmarinus officinalis L., essential oils, GC/MS, camphor

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Authors: Claire Williams

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Randomised controlled Trials (RCTs) of efficacy are still perceived as the gold standard for the generation of evidence, and whilst advances in data collection methods are well developed, this progress has not been matched for the reporting of adverse events (AEs). Assessment and reporting of AEs in clinical trials are fraught with human error and inefficiency and are extremely time and resource intensive. Recent research conducted into the quality of reporting of AEs during clinical trials concluded it is substandard and reporting is inconsistent. Investigators commonly send reports to sponsors who are incorrectly categorised and lacking in critical information, which can complicate the detection of valid safety signals. In our presentation, we will describe an electronic data capture system, which has been designed to support clinical trial processes by reducing the resource burden on investigators, improving overall trial efficiencies, and making trials safer for patients. This proprietary technology was developed using expertise proven in the delivery of the world’s first prospective, phase 3b real-world trial, ‘The Salford Lung Study, ’ which enabled robust safety monitoring and reporting processes to be accomplished by the remote monitoring of patients’ EHRs. This technology enables safety alerts that are pre-defined by the protocol to be detected from the data extracted directly from the patients EHR. Based on study-specific criteria, which are created from the standard definition of a serious adverse event (SAE) and the safety profile of the medicinal product, the system alerts the investigator or study team to the safety alert. Each safety alert will require a clinical review by the investigator or delegate; examples of the types of alerts include hospital admission, death, hepatotoxicity, neutropenia, and acute renal failure. This is achieved in near real-time; safety alerts can be reviewed along with any additional information available to determine whether they meet the protocol-defined criteria for reporting or withdrawal. This active surveillance technology helps reduce the resource burden of the more traditional methods of AE detection for the investigators and study teams and can help eliminate reporting bias. Integration of multiple healthcare data sources enables much more complete and accurate safety data to be collected as part of a trial and can also provide an opportunity to evaluate a drug’s safety profile long-term, in post-trial follow-up. By utilising this robust and proven method for safety monitoring and reporting, a much higher risk of patient cohorts can be enrolled into trials, thus promoting inclusivity and diversity. Broadening eligibility criteria and adopting more inclusive recruitment practices in the later stages of drug development will increase the ability to understand the medicinal products risk-benefit profile across the patient population that is likely to use the product in clinical practice. Furthermore, this ground-breaking approach to AE detection not only provides sponsors with better-quality safety data for their products, but it reduces the resource burden on the investigator and study teams. With the data taken directly from the source, trial costs are reduced, with minimal data validation required and near real-time reporting enables safety concerns and signals to be detected more quickly than in a traditional RCT.

Keywords: more comprehensive and accurate safety data, near real-time safety alerts, reduced resource burden, safer trials

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Authors: Loredana Elena Nita, Maria Bercea, Aurica P. Chiriac, Iordana Neamtu

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The paper is devoted to the behavior of gels based on poly(itaconic anhydride-co-3, 9-divinyl-2, 4, 8, 10-tetraoxaspiro (5.5) undecane) copolymers, with different ratio between the comonomers, and hyaluronic acid (HA). The gel formation was investigated by small-amplitude oscillatory shear measurements following the viscoelastic behavior as a function of gel composition, temperature and shear conditions. Hyaluronic acid was investigated in the same conditions and its rheological behavior is typical to viscous fluids. In the case of the copolymers, the ratio between the two comonomers influences the viscoelastic behavior, a higher content of itaconic anhydride favoring the gel formation. Also, the sol-gel transition was evaluated according to Winter-Chambon criterion that identifies the gelation point when the viscoelastic moduli (G’ and G”) behave similarly as a function of oscillation frequency. From rheological measurements, an optimum composition was evidenced for which the system presents a typical gel-like behavior at 37 °C: the elastic modulus is higher than the viscous modulus and they are not dependent on the oscillation frequency. The formation of the 3D macroporous network was also evidenced by FTIR spectra, SEM microscopy and chemical imaging. These hydrogels present a high potential as drug delivery systems.

Keywords: copolymer, viscoelasticity, gelation, 3D network

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Authors: Smita Chaudhary

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Traffic in India are observed uncontrolled, and are characterized by chaotic (not follows the lane discipline) traffic situation. Bus Rapid Transit (BRT) has emerged as a viable option to enhance transportation capacity and provide increased levels of mobility and accessibility. At present in Ahmadabad there are as many intersections which face the congestion and delay at signalized intersection due to transit (BRT) lanes. Most of the intersection in spite of being signalized is operated manually due to the conflict between BRT buses and heterogeneous traffic. Though BRTS in Ahmadabad has an exclusive lane of its own but with this comes certain limitations which Ahmadabad is facing right now. At many intersections in Ahmadabad due to these conflicts, interference, and congestion both heterogeneous traffic as well as transit buses suffer traffic delays of remarkable 3-4 minutes at each intersection which has a become an issue of great concern. There is no provision of BRT bus priority due to which existing signals have their least role to play in managing the traffic that ultimately call for manual operation. There is an immense decrement in the daily ridership of BRTS because people are finding this transit mode no more time saving in their routine, there is an immense fall in ridership ultimately leading to increased number of private vehicles, idling of vehicles at intersection cause air and noise pollution. In order to bring back these commuters’ transit facilities need to be improvised. Classified volume count survey, travel time delay survey was conducted and revised signal design was done for whole study stretch having three intersections and one roundabout, later one intersection was simulated in order to see the effect of giving priority to BRT on side street queue length and travel time for heterogeneous traffic. This paper aims at suggesting the recommendations in signal cycle, introduction of intermittent priority for transit buses, simulation of intersection in study stretch with proposed signal cycle using VISSIM in order to make this transit amenity feasible and attracting for commuters in Ahmadabad.

Keywords: BRT, priority, Ridership, Signal, VISSIM

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Authors: Huayang Yu, Nicola Ingram, David C. Green, Paul D. Thornton

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The dual stimuli-controlled release of doxorubicin from gel-embedded nanoparticles is reported. Non-cytotoxic polymer nanoparticles are formed from poly(ethylene glycol)-b-poly(benzyl glutamate) that, uniquely, contain a central ester link. This connection renders the nanoparticles pH-responsive, enabling extensive doxorubicin release in acidic solutions (pH 6.5), but not in solutions of physiological pH (pH 7.4). Doxorubicin loaded nanoparticles were found to be stable for at least 31 days and lethal against the three breast cancer cell lines tested. Furthermore, doxorubicin-loaded nanoparticles could be incorporated within a thermoresponsive poly(2-hydroxypropyl methacrylate) gel depot, which forms immediately upon injection of poly(2-hydroxypropyl methacrylate) into aqueous solution. The combination of the poly(2-hydroxypropyl methacrylate) gel and poly(ethylene glycol)-b-poly(benzyl glutamate) nanoparticles yields an injectable doxorubicin delivery system that facilities near-complete drug release when maintained at elevated temperatures (37 °C) in acidic solution (pH 6.5). In contrast, negligible payload release occurs when the material is stored at room temperature in a non-acidic solution (pH 7.4). The system has great potential as a vehicle for the prolonged, site-specific release of chemotherapeutics.

Keywords: biodegradable, nanoparticle, polymer, thermoresponsive

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Authors: Mitchell De Sousa

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The city of Buenos Aires and its agglomeration concentrates more than the thirty percent of the Argentine population. Historically, the political governments (essentially during the neoliberal ones) focused all the equipment, investment, progress on the north of the city since it is the place where all the financial, core services, and the main country harbor is. The south part of the town and all the cities around the south portion of it is has been, historically, where are concentrated the more vital unfulfilled needs of this population. The river that cross over the urban agglomeration of Buenos Aires, the Matanza-Riachuelo, has been historically a place of urban segregation since it is located south of the main town. From the post-colonial times, the river has been officially a place that separates the jurisdiction of the city of Buenos Aires with some of the towns that were built around the urban agglomeration. Since its place has never been treated as a whole and has always been treated as a boundary, there is always been a focus for factories to dispose its waste and an attractive place for a large portion of the underclasses to settled down there, occupying illegally the previous terrains that were once from the railway, now abandoned. Regarding those issues and adding a one more problematic one, those who lives beyond the boundary has few access to enter the main capital city. A few bridges connect some portions of it over the Matanza Riachuelo River, which there is also a limited accessibility to the main city from the south. Because of such, the main entrances to the town are always collapsed by all the services that the urban agglomeration offer (from buses to trains and individual cars). Beyond all the enlisted problems, the contamination of the river makes it one of the most contaminated rivers on the entire world. Those who lives in the settlements are in there for themselves, so the fight from them to their right of the city and their claims to the state for intervention in the urban coast is one of the most promising discussions surrounding this place of this urban agglomeration. The study focuses on the perception of those who lives in this boundary through interviews and collective experiences and is a part of a more developed project in the University of Buenos Aires study called ‘Urban landscape and a sustainable study through the interdisciplinary. Urban strategies on city borders’.

Keywords: Buenos Aires, landscape, mobility, popular sectors, urban segregation

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Authors: Y. Ruchi, A. Prerna, S. Deepshikha

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Amyotrophic lateral sclerosis (ALS), also known as “Lou Gehrig’s disease”. It is a neurodegenerative disease associated with degeneration of motor neurons in the cerebral cortex, brain stem, and spinal cord characterized by distal muscle weakness, atrophy, normal sensation, pyramidal signs and progressive muscular paralysis reflecting. ALS2 is a juvenile autosomal recessive disorder, slowly progressive, that maps to chromosome 2q33 and is associated with mutations in the alsin gene, a putative GTPase regulator. In this paper we have done homology modeling of alsin2 protein using multiple templates (3KCI_A, 4LIM_A, 402W_A, 4D9S_A, and 4DNV_A) designed using the Prime program in Schrödinger software. Further modeled structure is used to identify effective binding sites on the basis of structural and physical properties using sitemap program in Schrödinger software, structural and function analysis is done by using Prosite and ExPASy server that gives insight into conserved domains and motifs that can be used for protein classification. This paper summarizes the structural, functional and binding site property of alsin2 protein. These binding sites can be potential drug target sites and can be used for docking studies.

Keywords: ALS, binding site, homology modeling, neuronal degeneration

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Authors: R. Reshma srilakshmi, S. Shalini, P. Yogeeswari, D. Sriram

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Lysine aminotransferase is a crucial enzyme for dormancy in M. tuberculosis. It is involved in persistence and antibiotic resistance. In present work, we attempted to develop benzthiazole derivatives as lysine aminotransferase inhibitors. In our attempts, we also unexpectedly arrived at an interesting compound 21 (E)-4-(5-(2-(benzo[d]thiazol-2-yl)-2-cyanovinyl)thiophen-2-yl)benzoic acid which even though has moderate activity against persistent phase of mycobacterium, it has significant potency against active phase. In the entire series compound 22 (E)-4-(5-(2-(benzo[d]thiazol-2-yl)-2-cyanovinyl)thiophen-2-yl)isophthalic acid emerged as potent molecule with LAT IC50 of 2.62 µM. It has a significant log reduction of 2.9 and 2.3 fold against nutrient starved and biofilm forming mycobacteria. It was found to be inactive in MABA assay and M.marinum induced zebra fish model. It is also devoid of cytotoxicity. Compound 22 was also found to possess bactericidal effect which is independent of concentration and time. It was found to be effective in combination with Rifampicin in 3D granuloma model. The results are very encouraging as the hit molecule shows activity against active as well as persistent forms of tuberculosis. The identified hit needs further more pharmacokinetic and dynamic screening for development as new drug candidate.

Keywords: benzothiazole, latent tuberculosis, LAT, nutrient starvation

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Authors: Zimu Li, Zheng Wan

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The Suez Canal plays an important role in global shipping networks and is one of the most frequently used waterways in the world. The 2021 canal obstruction by ship Ever Given in March 2021, however, completed blocked the Suez Canal for a week and caused significant disruption to world trade. Therefore, it is very important to quantitatively analyze the impact of the accident on the robustness of the global shipping network. However, the current research on maritime transportation networks is usually limited to local or small-scale networks in a certain region. Based on the complex network theory, this study establishes a global shipping complex network covering 2713 nodes and 137830 edges by using the real trajectory data of the global marine transport ship automatic identification system in 2018. At the same time, two attack modes, deliberate (Suez Canal Blocking) and random, are defined to calculate the changes in network node degree, eccentricity, clustering coefficient, network density, network isolated nodes, betweenness centrality, and closeness centrality under the two attack modes, and quantitatively analyze the actual impact of Suez Canal Blocking on the robustness of global shipping network. The results of the network robustness analysis show that Suez Canal blocking was more destructive to the shipping network than random attacks of the same scale. The network connectivity and accessibility decreased significantly, and the decline decreased with the distance between the port and the canal, showing the phenomenon of distance attenuation. This study further analyzes the impact of the blocking of the Suez Canal on Chinese ports and finds that the blocking of the Suez Canal significantly interferes withChina's shipping network and seriously affects China's normal trade activities. Finally, the impact of the global supply chain is analyzed, and it is found that blocking the canal will seriously damage the normal operation of the global supply chain.

Keywords: global shipping networks, ship AIS trajectory data, main channel, complex network, eigenvalue change

Procedia PDF Downloads 182

Authors: Ankur Chaudhuri, Sibani Sen Chakraborty

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In human, glutaminyl cyclase activity is highly abundant in neuronal and secretory tissues and is preferentially restricted to hypothalamus and pituitary. The N-terminal modification of β-amyloids (Aβs) peptides by the generation of a pyro-glutamyl (pGlu) modified Aβs (pE-Aβs) is an important process in the initiation of the formation of neurotoxic plaques in Alzheimer’s disease (AD). This process is catalyzed by glutaminyl cyclase (QC). The expression of QC is characteristically up-regulated in the early stage of AD, and the hallmark of the inhibition of QC is the prevention of the formation of pE-Aβs and plaques. A computer-aided drug design (CADD) process was employed to give an idea for the designing of potentially active compounds to understand the inhibitory potency against human glutaminyl cyclase (QC). This work elaborates the ligand-based and structure-based pharmacophore exploration of glutaminyl cyclase (QC) by using the known inhibitors. Three dimensional (3D) quantitative structure-activity relationship (QSAR) methods were applied to 154 compounds with known IC50 values. All the inhibitors were divided into two sets, training-set, and test-sets. Generally, training-set was used to build the quantitative pharmacophore model based on the principle of structural diversity, whereas the test-set was employed to evaluate the predictive ability of the pharmacophore hypotheses. A chemical feature-based pharmacophore model was generated from the known 92 training-set compounds by HypoGen module implemented in Discovery Studio 2017 R2 software package. The best hypothesis was selected (Hypo1) based upon the highest correlation coefficient (0.8906), lowest total cost (463.72), and the lowest root mean square deviation (2.24Å) values. The highest correlation coefficient value indicates greater predictive activity of the hypothesis, whereas the lower root mean square deviation signifies a small deviation of experimental activity from the predicted one. The best pharmacophore model (Hypo1) of the candidate inhibitors predicted comprised four features: two hydrogen bond acceptor, one hydrogen bond donor, and one hydrophobic feature. The Hypo1 was validated by several parameters such as test set activity prediction, cost analysis, Fischer's randomization test, leave-one-out method, and heat map of ligand profiler. The predicted features were then used for virtual screening of potential compounds from NCI, ASINEX, Maybridge and Chembridge databases. More than seven million compounds were used for this purpose. The hit compounds were filtered by drug-likeness and pharmacokinetics properties. The selective hits were docked to the high-resolution three-dimensional structure of the target protein glutaminyl cyclase (PDB ID: 2AFU/2AFW) to filter these hits further. To validate the molecular docking results, the most active compound from the dataset was selected as a reference molecule. From the density functional theory (DFT) study, ten molecules were selected based on their highest HOMO (highest occupied molecular orbitals) energy and the lowest bandgap values. Molecular dynamics simulations with explicit solvation systems of the final ten hit compounds revealed that a large number of non-covalent interactions were formed with the binding site of the human glutaminyl cyclase. It was suggested that the hit compounds reported in this study could help in future designing of potent inhibitors as leads against human glutaminyl cyclase.

Keywords: glutaminyl cyclase, hit lead, pharmacophore model, simulation

Procedia PDF Downloads 131

Authors: Mabroka Omar Sherehe

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Despite the great efficacy of isoniazid (INH) and rifampicine (RIF) combination in the treatment of tuberculosis, hepatotoxicity is the most common serious complication. The potential protective effect of simvastatin (sim) against combination-induced hepatotoxicity was investigated in the present study. The administration of INH-RIF combination (50mg/kg each for 14 days) resulted in a significant increased activities of serum alanine and aspartate aminotransferases, such effects were further supported by histopathological studies. INH-RIF combination produced a significant increase in liver lipid, decreased SOD and CAT, and a significant depletion of GSH level. Additionally, treatment with INH-RIF combination resulted in a significant increase in liver MPO activity. The lipid-lowering drug, Sim demonstrated in the current study an evident antioxidant action, such effect was mediated via decreasing the elevated MDA, MPO, and restoring liver CAT activity. Additionally, Sim restored liver NO level to near basal value Furthermore, one cannot rule out the lipid-lowering effect of Sim that would probably add to its beneficial hepatoprotective antioxidant activity, where Sim decreased the elevated cholesterol, TGs and LDL cholesterol level and increased the serum HDL cholesterol level.

Keywords: isoniazid, rifampicine, oxidative stress, nitric oxide

Procedia PDF Downloads 616

Authors: Alexandra P. Alexandropoulou, Andreas Fousteris, Eleni Didaskalou, Dimitrios A. Georgakellos

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As urbanization is becoming a major stress factor not only for the urban environment but also for the wellbeing of city dwellers, incorporating the issues of urban health in strategic city planning and policy-making has never been more relevant. The impact of urbanization can vary from low to severe and relates to all non-communicable diseases caused by the different functions of cities. Air pollution, noise pollution, water and soil pollution, availability of open green spaces, and urban heat island are the major factors that can compromise citizens' health. Urban health describes the effects of the social environment, the physical environment, and the availability and accessibility to health and social services. To assess the quality of urban wellbeing, all urban characteristics that might have an effect on citizens' health must be considered, evaluated, and introduced in integrated local planning. A series of indices and indicators can be used to better describe these effects and set the target values in policy making. Local strategic planning is one of the most valuable development tools a local city administration can possess; thus, it has become mandatory under Greek law for all municipalities. It involves a two-stage procedure; the first aims to collect, analyse and evaluate data on the current situation of the city (administrative data, population data, environmental data, social data, swot analysis), while the second aims to introduce a policy vision described and supported by distinct (nevertheless integrated) actions, plans and measures to be implemented with the aim of city development and citizen wellbeing. In this procedure, the element of health is often neglected or under-evaluated. A relative survey was conducted among all Greek local authorities in order to shed light on the current situation. Evidence shows that the rate of incorporation of health in strategic planning is lacking behind. The survey also highlights key hindrances and concerns raised by local officials and suggests a path for the way forward.

Keywords: urban health, strategic planning, local authorities, integrated development

Procedia PDF Downloads 74

Authors: Anum Obaid, Bushra Noor, Zoshia Zainab

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In South Asian countries, Pakistan faces significant public health challenges regarding maternal and neonatal health (MNH). Despite global efforts to improve maternal, newborn, child, and health (MNCH) outcomes through initiatives like the Millennium Development Goals (MDGs) and Sustainable Development Goals (SDGs), high maternal and neonatal mortality rates persist. In patriarchal societies, cultural norms, family dynamics, and gender roles heavily influence healthcare accessibility and decision-making processes, often leading to delayed and inadequate maternal care. Addressing these socio-cultural barriers and enhancing healthcare resources is crucial to improving maternal health outcomes in areas like Faisalabad. A qualitative study was conducted involving two groups of informants: gynecologists practicing in private clinics and first-time pregnant women receiving care in government hospitals. Data collection included obtaining institutional permission, conducting semi-structured in-depth interviews, and using non-probability sampling techniques. A proactive strategy to overcome maternal health challenges involves using aversion therapy and disseminating knowledge among family members. This approach aims to foster a deep understanding within the family unit regarding the importance of maternal well-being, thereby creating a supportive environment and facilitating informed decision-making related to healthcare access and lifestyle choices. The findings indicate that maternal health is compromised both physiologically and psychologically, with significant implications for the baby's health. Mental well-being is profoundly affected, largely due to familial behavior and entrenched cultural taboos.

Keywords: maternal health, neonatal health, socio-cultural norms, primigravida women, gynecologist, familial conduct, cultural taboos

Procedia PDF Downloads 40

Authors: Lonna Mabandla, Godfrey Musvoto

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Transportation is a catalytic feature in cities. Transport and land use activity are interdependent and have a feedback loop between how land is developed and how transportation systems are designed and used. This recursive relationship between land use and transportation is reflected in how public transportation routes internal to the inner-city enhance accessibility, therefore creating spaces that are conducive to business activity, while the business activity also informs public transportation routes. It is for this reason that the focus of this research is on public transportation within inner-city areas where the dynamic is evident. Durban is the chosen case study where the dominating form of public transportation within the central business district (CBD) is minibus taxis. The paradox here is that minibus taxis still form part of the informal economy even though they are the leading form of public transportation in South Africa. There have been many attempts to formalise this industry to follow more regulatory practices, but minibus taxis are privately owned, therefore complicating any proposed intervention. The argument of this study is that the application of collaborative planning through a sustainable partnership between the public and private sectors will improve the social and environmental sustainability of public transportation. One of the major challenges that exist within such collaborative endeavors is power dynamics. As a result, a key focus of the study is on power relations. Practically, power relations should be observed over an extended period, specifically when the different stakeholders engage with each other, to reflect valid data. However, a lengthy data collection process was not possible to observe during the data collection phase of this research. Instead, interviews were conducted focusing on existing procedural planning practices between the inner-city minibus taxi association (South and North Beach Taxi Association), the eThekwini Transport Authority (ETA), and the eThekwini Town Planning Department. Conclusions and recommendations were then generated based on these data.

Keywords: collaborative planning, sustainability, public transport, minibus taxis

Procedia PDF Downloads 59

Authors: Yu Chen, Xiaoguang Yang, Lin Lin

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Traffic engineering construction is an important infrastructure for economic and social development. In the process of construction and operation, the ability to make a correct evaluation of the project's environmental impact appears to be crucial to the rational operation of existing transportation projects, the correct development of transportation engineering construction and the adoption of corresponding measures to scientifically carry out environmental protection work. Most of the existing research work on ecological and environmental impact assessment is limited to individual aspects of the environment and less to the overall evaluation of the environmental system; in terms of research conclusions, there are more qualitative analyses from the technical and policy levels, and there is a lack of quantitative research results and quantitative and operable evaluation models. In this paper, a comprehensive analysis of the ecological and environmental impacts of transportation construction projects is conducted, and factors such as the accessibility of data and the reliability of calculation results are comprehensively considered to extract indicators that can reflect the essence and characteristics. The qualitative evaluation indicators were screened using the expert review method, the qualitative indicators were measured using the fuzzy statistics method, the quantitative indicators were screened using the principal component analysis method, and the quantitative indicators were measured by both literature search and calculation. An environmental impact evaluation index system with the general objective layer, sub-objective layer and indicator layer was established, dividing the environmental impact of the transportation construction project into two periods: the construction period and the operation period. On the basis of the evaluation index system, the index weights are determined using the hierarchical analysis method, and the individual indicators to be evaluated are dimensionless, eliminating the influence of the original background and meaning of the indicators. Finally, the thesis uses the above research results, combined with the actual engineering practice, to verify the correctness and operability of the evaluation method.

Keywords: transportation construction projects, ecological and environmental impact, analysis and evaluation, indicator evaluation system

Procedia PDF Downloads 105

Authors: Megan E. Davies

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As substance use become an increasing prevalent occurrence amongst young people, prevention programs designed specifically for children and adolescents are required to protect against associated cognitive, psychological, and behavioural issues. Further, young people from marginalized backgrounds would highly benefit from culturally adapted substance use prevention programs. The first and second phase of the Life Skills Training (LST) program, the Maskwacis Life Skills Training (MLST) program, the Bii-Zin-Da-De-Da (BZDDD; “Listening to One Another”), and a culturally sensitive smoking prevention program, all of which have been adapted to Canadian Indigenous cultures and are applied within the school and family settings, are discussed. Additionally, comorbid disorders, at-risk personality types, and motivating factors associated with substance use amongst Canadian children and adolescents, specifically Indigenous youth, are explored through the application of a biopsychosocial model. Requital efforts being made in Canada towards Indigenous communities are described within a historical context, and substance use prevention programs targeting Indigenous children and adolescents are compared. Through this lens, suggestions are presented for future research on preventative interventions directed towards substance use within minority groups.

Keywords: early intervention, cultural appropriateness, life skills training, smoking prevention, drug and alcohol prevention

Procedia PDF Downloads 103

Authors: Figen Kadirgan, M. A. Neset Kadirgan, Gokcen A. Ciftcioglu

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Addressing food security and climate change challenges have to be done in an integrated manner. To increase food production and to reduce emissions intensity, thus contributing to mitigate climate change, food systems have to be more efficient in the use of resources. To ensure food security and adapt to climate change they have to become more resilient. The changes required in agricultural and food systems will require the creation of supporting institutions and enterprises to provide services and inputs to smallholders, fishermen and pastoralists, and transform and commercialize their production more efficiently. Thus there is continously growing need to switch to green economy where simultaneously causes reduction in carbon emissions and pollution, enhances energy and resource-use efficiency; and prevents the loss of biodiversity and ecosystem services. Smart Agriculture takes into account the four dimensions of food security, availability, accessibility, utilization, and stability. It is well known that, the increase in world population will strengthen the population-food imbalance. The emphasis on reduction of food losses makes a point on production, on farmers, on increasing productivity and income ensuring food security. Where also small farmers enhance their income and stabilize their budget. The use of solar drying for agricultural, marine or meat products is very important for preservation. Traditional sun drying is a relatively slow process where poor food quality is seen due to an infestation of insects, enzymatic reactions, microorganism growth and micotoxin development. In contrast, solar drying has a sound solution to all these negative effects of natural drying and artificial mechanical drying. The technical directions in the development of solar drying systems for agricultural products are compact collector design with high efficiency and low cost. In this study, using solar selective surface produced in Selektif Teknoloji Co. Inc. Ltd., solar dryers with high efficiency will be developed and a feasibility study will be realized.

Keywords: energy, renewable energy, solar collector, solar drying

Procedia PDF Downloads 225

Authors: Matthew Scott Lau

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This study addresses the research question: How effective has the Community Health Assist Scheme (CHAS) been in reducing market failure in Singapore’s healthcare sector? The CHAS policy, introduced in 2012 in Singapore, aims to improve accessibility and affordability of healthcare by offering subsidies to low and middle-income groups and elderly individuals for general practice consultations and healthcare. The investigation was undertaken by acquiring and analysing primary and secondary research data from 3 main sources, including handwritten survey responses of 334 individuals who were valid CHAS subsidy recipients (CHAS cardholders) from 5 different locations in Singapore, interview responses from two established general practitioner doctors with working knowledge of the scheme, and information from literature available online. Survey responses were analysed to determine how CHAS has affected the affordability and consumption of healthcare, and other benefits or drawbacks for CHAS users. The interview responses were used to explain the benefits of healthcare consumption and provide different perspectives on the impacts of CHAS on the various parties involved. Online sources provided useful information on changes in healthcare consumerism and Singapore’s government policies. The study revealed that CHAS has been largely effective in reducing market failure as the subsidies granted to consumers have improved the consumption of healthcare. This has allowed for the external benefits of healthcare consumption to be realized, thus reducing market failure. However, the study also revealed that CHAS cannot be fully effective in reducing market failure as the scope of CHAS prevents healthcare consumption from fully reaching the socially optimal level. Hence, the study concluded that CHAS has been effective to a large extent in reducing market failure in Singapore’s healthcare sector, albeit with some benefits to third parties yet to be realised. There are certain elements of the investigation, which may limit the validity of the conclusion, such as the means used to determine the socially optimal level of healthcare consumption, and the survey sample size.

Keywords: healthcare consumption, health economics, market failure, subsidies

Procedia PDF Downloads 159