Search results for: rapid microbial identification

Authors: Justin A. Udie, Subhes C. Bhatthacharyya, Leticia Ozawa-Meida

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The impact of climate change is severe in the Niger Delta and critical oil and gas infrastructures are vulnerable. This is partly due to lack of specific impact assessment framework to assess impact indices on both existing and new infrastructures. The purpose of this paper is to develop a framework for the assessment of climate change impact on critical oil and gas infrastructure in the region. Comparative and documentary methods as well as analysis of frameworks were used to develop a flexible, integrated and conceptual four dimensional framework underpinning; 1. Scoping – the theoretical identification of inherent climate burdens, review of exposure, adaptive capacities and delineation of critical infrastructure; 2. Vulnerability assessment – presents a systematic procedure for the assessment of infrastructure vulnerability. It provides real time re-scoping, practical need for data collection, analysis and review. Physical examination of systems is encouraged to complement the scoped data and ascertain the level of exposure to relevant climate risks in the area; 3. New infrastructure – consider infrastructures that are still at developmental level. It seeks to suggest the inclusion of flexible adaptive capacities in original design of infrastructures in line with climate threats and projections; 4. The Mainstreaming Climate Impact Assessment into government’s environmental decision making approach. Though this framework is designed specifically for the estimation of exposure, adaptive capacities and criticality of vulnerable oil and gas infrastructures in the Niger Delta to climate burdens; it is recommended for researchers and experts as a first-hand generic and practicable tool which can be used for the assessment of other infrastructures perceived as critical and vulnerable. The paper does not provide further tools that synch into the methodological approach but presents pointers upon which a pragmatic methodology can be developed.

Keywords: adaptation, assessment, conceptual, climate, change, framework, vulnerability

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Authors: Ling Liyun

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In the field of contemporary architecture, complex forms of architectural works continue to emerge in the world, along with some new terminology emerged: digital architecture, parametric design, algorithm generation, building information modeling, CNC construction and so on. Architects gradually mastered the new skills of mathematical logic in the form of exploration, virtual simulation, and the entire design and coordination in the construction process. Digital construction technology has a greater degree in controlling construction, and ensure its accuracy, creating a series of new construction techniques. As a result, the use of digital technology is an improvement and expansion of the practice of digital architecture design revolution. We worked by reading and analyzing information about the digital architecture development process, a large number of cases, as well as architectural design and construction as a whole process. Thus current developments were introduced and discussed in our paper, such as architectural discourse, design theory, digital design models and techniques, material selecting, as well as artificial intelligence space design. Our paper also pays attention to the representative three cases of digital design and construction experiment at great length in detail to expound high-informatization, high-reliability intelligence, and high-technique in constructing a humane space to cope with the rapid development of urbanization. We concluded that the opportunities and challenges of the shift existed in architectural paradigms, such as the cooperation methods, theories, models, technologies and techniques which were currently employed in digital design research and digital praxis. We also find out that the innovative use of space can gradually change the way people learn, talk, and control information. The past two decades, digital technology radically breaks the technology constraints of industrial technical products, digests the publicity on a particular architectural style (era doctrine). People should not adapt to the machine, but in turn, it’s better to make the machine work for users.

Keywords: artificial intelligence, collaboration, digital architecture, digital design theory, material selection, space construction

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Authors: Christian Fercher, Jiaul Islam, Simon R. Corrie

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Fluorescence-based immunodiagnostics are an emerging field in biosensor development and exhibit several advantages over traditional detection methods. While various affinity biosensors have been developed to generate a fluorescence signal upon sensing varying concentrations of analytes, reagentless, reversible, and continuous monitoring of complex biological samples remains challenging. Here, we aimed to genetically engineer biosensors based on single-chain antibody fragments (scFv) that are site-specifically labeled with environmentally sensitive fluorescent unnatural amino acids (UAA). A rational design approach resulted in quantifiable analyte-dependent changes in peak fluorescence emission wavelength and enabled antigen detection in vitro. Incorporation of a polarity indicator within the topological neighborhood of the antigen-binding interface generated a titratable wavelength blueshift with nanomolar detection limits. In order to ensure continuous analyte monitoring, scFv candidates with fast binding and dissociation kinetics were selected from a genetic library employing a high-throughput phage display and affinity screening approach. Initial rankings were further refined towards rapid dissociation kinetics using bio-layer interferometry (BLI) and surface plasmon resonance (SPR). The most promising candidates were expressed, purified to homogeneity, and tested for their potential to detect biomarkers in a continuous microfluidic-based assay. Variations of dissociation kinetics within an order of magnitude were achieved without compromising the specificity of the antibody fragments. This approach is generally applicable to numerous antibody/antigen combinations and currently awaits integration in a wide range of assay platforms for one-step protein quantification.

Keywords: antibody engineering, biosensor, phage display, unnatural amino acids

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Authors: Kuni Vergauwen, Ivan P. J. Huijnen, Astrid Depuydt, Jasmine Van Regenmortel, Mira Meeus

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A lower activity level and imbalanced activity pattern are frequently observed in persons with chronic fatigue syndrome (CFS) / myalgic encephalomyelitis (ME) due to debilitating fatigue and post-exertional malaise (PEM). Identification of measurement instruments to evaluate the activity level and pattern is therefore important. The objective is to identify measurement instruments suited to evaluate the activity level and/or pattern in patients with CFS/ME and review their psychometric properties. A systematic literature search was performed in the electronic databases PubMed and Web of Science until 12 October 2016. Articles including relevant measurement instruments were identified and included for further analysis. The psychometric properties of relevant measurement instruments were extracted from the included articles and rated based on the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist. The review was performed and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A total of 49 articles and 15 unique measurement instruments were found, but only three instruments were evaluated in patients with CFS/ME: the Chronic Fatigue Syndrome-Activity Questionnaire (CFS-AQ), Activity Pattern Interview (API) and International Physical Activity Questionnaire-Short Form (IPAQ-SF), three self-report instruments measuring the physical activity level. The IPAQ-SF, CFS-AQ and API are all equally capable of evaluating the physical activity level, but none of the three measurement instruments are optimal to use. No studies about the psychometric properties of activity monitors in patients with CFS/ME were found, although they are often used as the gold standard to measure the physical activity pattern. More research is needed to evaluate the psychometric properties of existing instruments, including the use of activity monitors.

Keywords: chronic fatigue syndrome, data collection, physical activity, psychometrics

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Authors: Magdalena Rusady Goey, Gordon Strathdee, Neil Perkins

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Background: Acute lymphoblastic leukaemia (ALL) is the most frequent type of childhood malignancy, accounting for 25% of all cases. TWIST2, a basic helix-loop-helix transcription factor, has been implicated in ALL development. Prior studies found that TWIST2 undergoes epigenetic silencing in more than 50% cases of ALL through promoter hypermethylation and suggested that re-expression of TWIST2 may inhibit cell growth/survival of leukaemia cell lines. TWIST2 has also been implicated as a regulator of NF-kappaB activity, which is constitutively active in leukaemia. Here, we use a lentiviral transductions system to confirm the importance of TWIST2 in controlling leukaemia cell growth and to investigate whether this is achieved through altered regulation of NF-kappaB activity. Method: Re-expression of TWIST2 in leukaemia cell lines was achieved using lentiviral-based transduction. The lentiviral vector also expresses enhanced green fluorescent protein (eGFP), allowing transduced cells to be tracked using flow cytometry. Analysis of apoptosis and cell proliferation were done using annexinV and VPD450 staining, respectively. Result and Discussion: TWIST2-expressing cells were rapidly depleted from a mixed population in ALL cell lines (NALM6 and Reh), indicating that TWIST2 inhibited cell growth/survival of ALL cells. In contrast, myeloid cell lines (HL60 and K562) were comparatively insensitive to TWIST2 re-expression. Analysis of apoptosis and cell proliferation found no significant induction of apoptosis, but did find a rapid induction of proliferation arrest in TWIST2-expressing Reh and NALM6 cells. Initial experiment with NF-kappaB inhibitor demonstrated that inhibition of NF-kappaB has similar impact on cell proliferation in the ALL cell lines, suggesting that TWITST2 may induce cell proliferation arrest through inhibition of NF-kappaB. Conclusion: The results of this study suggest that epigenetic inactivation of TWIST2 in primary ALL leads to increased proliferation, potentially by altering the regulation of NF-kappaB.

Keywords: leukaemia, acute lymphoblastic leukaemia, NF-kappaB, TWIST2, lentivirus

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Authors: Helen K. Buteme, Rebecca Axelsson-Robertson, Moses L. Joloba, Henry W. Boom, Gunilla Kallenius, Markus Maeurer

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Background: The Ugandan population is heavily affected by infectious diseases and Human leukocyte antigen (HLA) diversity plays a crucial role in the host-pathogen interaction and affects the rates of disease acquisition and outcome. The identification of HLA class 1 alleles and determining which alleles are associated with tuberculosis (TB) outcomes would help in screening individuals in TB endemic areas for susceptibility to TB and to predict resistance or progression to TB which would inevitably lead to better clinical management of TB. Aims: To be able to determine the HLA class 1 phenotype distribution in a Ugandan TB cohort and to establish the relationship between these phenotypes and active and latent TB. Methods: Blood samples were drawn from 32 HIV negative individuals with active TB and 45 HIV negative individuals with latent MTB infection. DNA was extracted from the blood samples and the DNA samples HLA typed by the polymerase chain reaction-sequence specific primer method. The allelic frequencies were determined by direct count. Results: HLA-A*02, A*01, A*74, A*30, B*15, B*58, C*07, C*03 and C*04 were the dominant phenotypes in this Ugandan cohort. There were differences in the distribution of HLA types between the individuals with active TB and the individuals with LTBI with only HLA-A*03 allele showing a statistically significant difference (p=0.0136). However, after FDR computation the corresponding q-value is above the expected proportion of false discoveries (q-value 0.2176). Key findings: We identified a number of HLA class I alleles in a population from Central Uganda which will enable us to carry out a functional characterization of CD8+ T-cell mediated immune responses to MTB. Our results also suggest that there may be a positive association between the HLA-A*03 allele and TB implying that individuals with the HLA-A*03 allele are at a higher risk of developing active TB.

Keywords: HLA, phenotype, tuberculosis, Uganda

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Authors: Sherly M. A., Subhankar Karmakar, Terence Chan, Christian Rau

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Floods are one of the most frequent natural disasters, causing widespread devastation, economic damage and threat to human lives. Hydrologic impacts of climate change and intensification of urbanization are two root causes of increased flood occurrences, and recent research trends are oriented towards understanding these aspects. Due to rapid urbanization, population of cities across the world has increased exponentially leading to improperly planned developments. Climate change due to natural and anthropogenic activities on our environment has resulted in spatiotemporal changes in rainfall patterns. The combined effect of both aggravates the vulnerability of urban populations to floods. In this context, an efficient and effective flood risk management with its core component as flood risk mapping is essential in prevention and mitigation of flood disasters. Urban flood risk mapping involves zoning of an urban region based on its flood risk, which depicts the spatiotemporal pattern of frequency and severity of hazards, exposure to hazards, and degree of vulnerability of the population in terms of socio-economic, environmental and infrastructural aspects. Although vulnerability is a key component of risk, its assessment and mapping is often less advanced than hazard mapping and quantification. A synergic effort from technical experts and social scientists is vital for the effectiveness of flood risk management programs. Despite an increasing volume of quality research conducted on urban flood risk, a comprehensive multidisciplinary approach towards flood risk mapping still remains neglected due to which many of the input parameters and definitions of flood risk concepts are imprecise. Thus, the objectives of this review are to introduce and precisely define the relevant input parameters, concepts and terms in urban flood risk mapping, along with its methodology, current status and limitations. The review also aims at providing thought-provoking insights to potential future researchers and flood management professionals.

Keywords: flood risk, flood hazard, flood vulnerability, flood modeling, urban flooding, urban flood risk mapping

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Authors: Binh T. T. Nguyen, Zhenyu Li, Eric Yap, Yi Zhang, Ai-Qun Liu

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Silicon-photonic-sensor system is an emerging class of analytical technologies that use evanescent field wave to sensitively measure the slight difference in the surrounding environment. The wavelength shift induced by local refractive index change is used as an indicator in the system. These devices can be served as sensors for a wide variety of chemical or biomolecular detection in clinical and environmental fields. In our study, a system including a silicon-based micro-ring resonator, microfluidic channel, and optical processing is designed, fabricated for biomolecule detection. The system is demonstrated to detect Clostridium botulinum type A neurotoxin (BoNT) in different water sources. BoNT is one of the most toxic substances known and relatively easily obtained from a cultured bacteria source. The toxin is extremely lethal with LD50 of about 0.1µg/70kg intravenously, 1µg/ 70 kg by inhalation, and 70µg/kg orally. These factors make botulinum neurotoxins primary candidates as bioterrorism or biothreat agents. It is required to have a sensing system which can detect BoNT in a short time, high sensitive and automatic. For BoNT detection, silicon-based micro-ring resonator is modified with a linker for the immobilization of the anti-botulinum capture antibody. The enzymatic reaction is employed to increase the signal hence gains sensitivity. As a result, a detection limit to 30 pg/mL is achieved by our silicon-photonic sensor within a short period of 80 min. The sensor also shows high specificity versus the other type of botulinum. In the future, by designing the multifunctional waveguide array with fully automatic control system, it is simple to simultaneously detect multi-biomaterials at a low concentration within a short period. The system has a great potential to apply for online, real-time and high sensitivity for the label-free bimolecular rapid detection.

Keywords: biotoxin, photonic, ring resonator, sensor

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Authors: Alex Knighton, Roba Khundkar, Michael Dunn

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Neo-colonialism is defined as the use of economic, political, cultural, or other pressures to control or influence other countries, especially former dependencies, and concerns have been raised about its presence in surgical missions. Surgical missions aim to rectify the huge disparity in surgical access worldwide, but their ethics must be carefully considered. This is especially in light of colonial history which affects international relations and global health today, to ensure that colonial attitudes are not influencing efforts to promote equity. This review examines the history of colonial global health, demonstrating that global health initiatives have consistently been used to benefit those providing them, and then asks whether elements of colonialism are still pervasive in surgical missions today. Data was collected from the literature using specified search terms and snowball searching, as well as from international expert web-based conferences on global surgery ethics. A thematic analysis was then conducted on this data, resulting in the identification of six themes which are identifiable in both past and present global health initiatives. These six themes are power, lack of understanding or respect, feelings of superiority, exploitation, enabling of dependency, and acceptance of poorer standards of care. An ethical analysis follows, concluding that the concerns of power and neo-colonialism in global surgery would be addressed by adopting a framework of procedural justice that promotes a refined governance process in which stakeholders are able to propose and reject decisions that affect them. The paper argues that adopting this model would address concerns of the power disparity in the field directly, as well as promoting an ethical framework to enable the other concerns of power disparity and neo-colonialism identified in the present analysis to be addressed.

Keywords: medical ethics, global surgery, global health, neocolonialism, surgical missions

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Authors: Yong-Kian Lim, Khan Cheung, Xin Dang, Steven Roberts, Xiaotong Wang, Vengatesen Thiyagarajan

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Unprecedented rate of increased CO₂ level in the ocean and the subsequent changes in carbonate system including decreased pH, known as ocean acidification (OA), is predicted to disrupt not only the calcification process but also several other physiological and developmental processes in a variety of marine organisms, including edible oysters. Nonetheless, not all species are vulnerable to those OA threats, e.g., some species may be able to cope with OA stress using environmentally induced modifications on gene and protein expressions. For example, external environmental stressors, including OA, can influence the addition and removal of methyl groups through epigenetic modification (e.g., DNA methylation) process to turn gene expression “on or off” as part of a rapid adaptive mechanism to cope with OA. In this study, the above hypothesis was tested through testing the effect of OA, using decreased pH 7.4 as a proxy, on the DNA methylation pattern of an endemic and a commercially important estuary oyster species, Crassostrea hongkongensis, at the time of larval habitat selection and metamorphosis. Larval growth rate did not differ between control pH 8.1 and treatment pH 7.4. The metamorphosis rate of the pediveliger larvae was higher at pH 7.4 than those in control pH 8.1; however, over one-third of the larvae raised at pH 7.4 failed to attach to an optimal substrate as defined by biofilm presence. During larval development, a total of 130 genes were differentially methylated across the two treatments. The differential methylation in the larval genes may have partially accounted for the higher metamorphosis success rate under decreased pH 7.4 but with poor substratum selection ability. Differentially methylated loci were concentrated in the exon regions and appear to be associated with cytoskeletal and signal transduction, oxidative stress, metabolic processes, and larval metamorphosis, which implies the high potential of C. hongkongensis larvae to acclimate and adapt through non-genetic ways to OA threats within a single generation.

Keywords: adaptive plasticity, DNA methylation, larval metamorphosis, ocean acidification

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Authors: Muhammad Nasar-U-Minallah, Dagmar Haase, Salman Qureshi, Safdar Ali Shirazi

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Urban green spaces (UGS) play a key role in the urban ecology of an area since they provide significant ecological services to compensate for natural environment functions damaged by the rapid growth of urbanization. The transformation of urban green specs to impervious landscapes has been recognized as a key factor prompting the distinctive urban heat and associated microclimatic changes. There is no doubt that urban green spaces offer a range of ecosystem services that can help to mitigate the ill effects of urbanization, heat anomalies, and climate change. The present study attempts to appraise the impact of urban green spaces on the urban thermal environment for the development of the microclimatic conditions in Lahore, Pakistan. The influence of urban heat has been studied through Landsat 8 data. The land surface temperature (LST) of Lahore was computed through the Radiative transfer method (RTM). The spatial variation of land surface temperature is retrieved to describe their local heat effect on urban microclimate. The association between the LST, normalized difference vegetation index, and the normalized difference built-up index are investigated to explore the impact of the urban green spaces and impervious surfaces on urban microclimate. The results of this study show significant changes in (impervious land surface 18% increase) land use within the study area. However, conversion of natural green cover to commercial and residential uses considerably increases the LST. Furthermore, results show that green spaces were the major heat sinks while impervious landscapes were the major heat source in the study area. Urban green spaces reveal 1 to 3℃ lower LST associated with their surrounding urban built-up area. This study shows that urban green spaces will help to mitigate the effect of urban microclimate and it is significant for the sustainable urban environment as well as to improve the quality of life of the urban inhabitants.

Keywords: thermal environmental, urban green space, cooling effect, microclimate, Lahore

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Authors: Tooba Sabir, Asima Jaffar, Namra Sabir, Mohammad Amjad Sabir

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Ecocriticism is the study of relationship between human and environment which has been represented in literature since the very beginning in pastoral tradition. However, the analysis of such representation is new as compared to the other critical evaluations like Psychoanalysis, Marxism, Post-colonialism, Modernism and many others. Ecocritics seek to find information like anthropocentrism, ecocentrism, ecofeminism, eco-Marxism, representation of environment and environmental concept and several other topics. In the current study the representation of environmental concepts, were ecocritically analyzed in Paulo Coelho’s The Alchemist, one of the most read novels throughout the world, having been translated into many languages. Analysis of the text revealed, the representations of environmental ideas like landscapes and tourism, biodiversity, land-sea displacement, environmental disasters and warfare, desert winds and sand dunes. 'This desert was once a sea' throws light on different theories of land-sea displacement, one being the plate-tectonic theory which proposes Earth’s lithosphere to be divided into different large and small plates, continuously moving toward, away from or parallel to each other, resulting in land-sea displacement. Another theory is the continental drift theory which holds onto the belief that one large landmass—Pangea, broke down into smaller pieces of land that moved relative to each other and formed continents of the present time. The cause of desertification may, however, be natural i.e. climate change or artificial i.e. by human activities. Imagery of the environmental concepts, at some instances in the novel, is detailed and at other instances, is not as striking, but still is capable of arousing readers’ imagination. The study suggests that ecocritical justifications of environmental concepts in the text will increase the interactions between literature and environment which should be encouraged in order to induce environmental awareness among the readers.

Keywords: biodiversity, ecocritical analysis, ecocriticism, environmental disasters, landscapes

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Authors: Nayab Kanwal, Noor Us Saher

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The management and utilization of food resources is becoming a big issue due to rapid urbanization, wastage and non-sustainable use of food, especially in developing countries. Therefore, the use of seafood as alternative sources is strongly promoted worldwide. Marine pollution strongly affects marine organisms, which ultimately decreases their export quality. The monitoring of contamination in marine organisms is a good indicator of the environmental quality as well as seafood quality. Monitoring the accumulation of chemical elements within various tissues of organisms has become a useful tool to survey current or chronic levels of heavy metal exposure within an environment. In this perspective, this study was carried out to compare the previous and current levels (Year 2012 and 2014) of heavy metals (Cd, Pb, Cr, Cu and Zn) in crabs marketed in Karachi and to estimate the toxicological risk associated with their intake. The accumulation of metals in marine organisms, both essential (Cu and Zn) and toxic (Pb, Cd and Cr), natural and anthropogenic, is an actual food safety issue. Significant (p>0.05) variations in metal concentrations were found in all crab species between the two years, with most of the metals showing high accumulation in 2012. For toxicological risk assessment, EWI (Estimated weekly intake), Target Hazard quotient (THQ) and cancer risk (CR) were also assessed and high EWI, Non- cancer risk (THQ < 1) showed that there is no serious threat associated with the consumption of shellfish species on Karachi coast. The Cancer risk showed the highest risk from Cd and Pb pollution if consumed in excess. We summarize key environmental health research on health effects associated with exposure to contaminated seafood. It could be concluded that considering the Pakistan coast, these edible species may be sensitive and vulnerable to the adverse effects of environmental contaminants; more attention should be paid to the Pb and Cd metal bioaccumulation and to toxicological risks to seafood and consumers.

Keywords: cancer risk, edible crabs, heavy metals pollution, risk assessment

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Authors: Abhishek N. Srivastava, Rahul Singh, Sumedha Chakma

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The rapid urbanization in the developing countries is generating an enormous amount of waste leading to the creation of unregulated landfill sites at various places at its disposal. The liquid waste, known as leachate, produced from these landfills sites is severely affecting the surrounding water quality. The water quality in the proximity areas of the landfill is found affected by various physico-chemical parameters of leachate such as pH, alkalinity, total hardness, conductivity, chloride, total dissolved solids (TDS), total suspended solids (TSS), sulphate, nitrate, phosphate, fluoride, sodium and potassium, biological parameters such as biochemical oxygen demand (BOD), chemical oxygen demand (COD), Faecal coliform, and heavy metals such as cadmium (Cd), lead (Pb), iron (Fe), mercury (Hg), arsenic (As), cobalt (Co), manganese (Mn), zinc (Zn), copper (Cu), chromium (Cr), nickel (Ni). However, all these parameters are distributive in leachate that produced according to the nature of waste being dumped at various landfill sites, therefore, it becomes very difficult to predict the main responsible parameter of leachate for water quality contamination. The present study is endeavour the comparative analysis of the physical, chemical and biological parameters of various landfills in India viz. Okhla landfill, Ghazipur landfill, Bhalswa ladfill in NCR Delhi, Deonar landfill in Mumbai, Dhapa landfill in Kolkata and Kodungayaiyur landfill, Perungudi landfill in Chennai. The statistical analysis of the parameters was carried out using the Statistical Packages for the Social Sciences (SPSS) and LandSim 2.5 model to simulate the long term effect of various parameters on different time scale. Further, the uncertainties characterization of various input parameters has also been analysed using fuzzy alpha cut (FAC) technique to check the sensitivity of various water quality parameters at the proximity of numerous landfill sites. Finally, the study would help to suggest the best method for the prevention of pollution migration from the landfill sites on priority basis.

Keywords: landfill leachate, water quality, LandSim, fuzzy alpha cut

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Authors: Seon-Young Lee, Harkiran Sagoo, Reem Farwana, Katharine Whitehurst, Alex Fowler, Riaz Agha

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Background/Aims: Systematic reviews and meta-analysis are becoming increasingly important way of summarizing research evidence. Researches in ophthalmology may represent further challenges, due to their potential complexity in study design. The aim of our study was to determine the reporting quality of systematic reviews and meta-analysis in ophthalmology with the PRISMA statement, by assessing the articles published between 2010 and 2015 from five major journals with the highest impact factor. Methods: MEDLINE and EMBASE were used to search systematic reviews published between January 2010 and December 2015, in 5 major ophthalmology journals: Progress in Retinal and Eye Research, Ophthalmology, Archives of Ophthalmology, American Journal of Ophthalmology, Journal of the American Optometric Association. Screening, identification, and scoring of articles were performed independently by two teams, followed by statistical analysis including the median, range, and 95% CIs. Results: 115 articles were involved. The median PRISMA score was 15 of 27 items (56%), with a range of 5-26 (19-96%) and 95% CI 13.9-16.1 (51-60%). Compliance was highest in items related to the description of rationale (item 3,100%) and inclusion of a structured summary in the abstract (item 2, 90%), while poorest in indication of review protocol and registration (item 5, 9%), specification of risk of bias affecting the cumulative evidence (item 15, 24%) and description of clear objectives in introduction (item 4, 26%). Conclusion: The reporting quality of systematic reviews and meta-analysis in ophthalmology need significant improvement. While the use of PRISMA criteria as a guideline before journal submission is recommended, additional research identifying potential barriers may be required to improve the compliance to the PRISMA guidelines.

Keywords: systematic reviews, meta-analysis, research methodology, reporting quality, PRISMA, ophthalmology

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Authors: Anu S. Nair, V. Anantha Subramanian

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This paper presents a surface development and fairing technique combining the features of a modern computer-aided design tool namely the Non-Uniform Rational Basis Spline (NURBS) with an algorithm to obtain a rapidly faired hull form. Some of the older series based designs give sectional area distribution such as in the Wageningen-Lap Series. Others such as the FORMDATA give more comprehensive offset data points. Nevertheless, this basic data still requires fairing to obtain an acceptable faired hull form. This method uses the input of sectional area distribution as an example and arrives at the faired form. Characteristic section shapes define any general ship hull form in the entrance, parallel mid-body and run regions. The method defines a minimum of control points at each section and using the Golden search method or the bisection method; the section shape converges to the one with the prescribed sectional area with a minimized error in the area fit. The section shapes combine into evolving the faired surface by NURBS and typically takes 20 iterations. The advantage of the method is that it is fast, robust and evolves the faired hull form through minimal iterations. The curvature criterion check for the hull lines shows the evolution of the smooth faired surface. The method is applicable to hull form from any parent series and the evolved form can be evaluated for hydrodynamic performance as is done in more modern design practice. The method can handle complex shape such as that of the bulbous bow. Surface patches developed fit together at their common boundaries with curvature continuity and fairness check. The development is coded in MATLAB and the example illustrates the development of the method. The most important advantage is quick time, the rapid iterative fairing of the hull form.

Keywords: computer-aided design, methodical series, NURBS, ship design

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Authors: Qin Yang, Fan Zhang, Juan Du, Chongkui Sun, Krishna Kota, Yun-Ling Zheng

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Telomeres are specialized structures at chromosome ends consisting of tandem repetitive DNA sequences [(TTAGGG)n in humans] and associated proteins, which are necessary for telomere function. Telomere lengths are tightly regulated within a narrow range in normal human somatic cells, the basis of cellular senescence and aging. Previous studies have extensively focused on how short telomeres are extended and have demonstrated that telomerase plays a central role in telomere maintenance through elongating the short telomeres. However, the molecular mechanisms of regulating excessively long telomeres are unknown. Here, we found that telomerase enzymatic component hTERT plays a dual role in the regulation of telomeres length. We analyzed single telomere alterations at each chromosomal end led to the discoveries that hTERT shortens excessively long telomeres and elongates short telomeres simultaneously, thus maintaining the optimal telomere length at each chromosomal end for an efficient protection. The hTERT-mediated telomere shortening removes large segments of telomere DNA rapidly without inducing telomere dysfunction foci or affecting cell proliferation, thus it is mechanistically distinct from rapid telomere deletion. We found that expression of hTERT generates telomeric circular DNA, suggesting that telomere homologous recombination may be involved in this telomere shortening process. Moreover, the hTERT-mediated telomere shortening is required its enzymatic activity, but telomerase RNA component hTR is not involved in it. Furthermore, shelterin protein TPP1 interacts with hTERT and recruits it on telomeres to mediate telomere shortening. In addition, telomere-associated proteins, DKC1 and TCAB1 also play roles in this process. This novel hTERT-mediated telomere shortening mechanism not only exists in cancer cells, but also in primary human cells. Thus, the hTERT-mediated telomere shortening is expected to shift the paradigm on current molecular models of telomere length maintenance, with wide-reaching consequences in cancer and aging fields.

Keywords: aging, hTERT, telomerase, telomeres, human cells

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Authors: Perdana Rakhmana Putra, Hansen Wijaya, Sri Budiyani, Muhamad Natsir, Alexis badai Samudra

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The Palembang Sub-Basin (PSB) located in southern part of South Sumatera basin (SSB) consist of half-graben complex trending N-S to NW-SE. These geometries are believe as an impact of strike-slip regime developed in Eocene-Oligocene. Generally, most of the wells in this area produced hydrocarbon from late stage of syn-rift sequences called Lower Talang Akar (LTAF) and post-rift sequences called Batu Raja Formation (BRF) and drilled to proved hydrocarbon on structural trap; three-way dip anticline, four-way dip anticline, dissected anticline, and stratigraphy trap; carbonate build-up and stratigraphic pinch out. Only a few wells reached the deeper syn-rift sequences called Lahat Formation (LAF) and Lemat Formation (LEF). The new interpretation of subsurface data was done by the tectonostratigraphy concept and focusing on syn-rift sequence. Base on seismic characteristic on basin centre, it divided into four sequences: pre-rift sequence, rift initiation, maximum rift and late rift. These sequences believed as a new exploration target on PSB mature basin. This paper will demonstrate the paleo depositional setting during Paleogene and exploration play concept of syn-rift sequence in PSB. The main play for this area consists of stratigraphic and structure play, where the stratigraphic play is Eocene-Oligocene sediment consist of LAF sandstone, LEF-Benakat formation, and LAF with pinch-out geometry. The pinch-out, lenses geometry and on-lap features can be seen on the seismic reflector and formed at the time of the syn-rift sequence. The structural play is dominated by a 3 Way Dip play related to reverse fault trap.

Keywords: syn-rift, tectono-stratigraphy, exploration play, basin center play, south sumatera basin

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Authors: Faiza Marrium, Masood Rabbani, Ali Ahmad Sheikh, Muhammad Yasin Tipu Javed Muhammad, Sohail Raza

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More than 75% diseases spreading in the past 10 years in human population globally are linked to veterinary sector. Veterinary diagnostic labs are the powerful ally for diagnosis, prevention and monitoring of animal diseases in any country. In order to avoid detrimental effects of errors in disease diagnostic and biorisk management, there is a dire need to establish quality control system. In current study, 3 private and 6 public sectors veterinary diagnostic labs were selected for survey. A questionnaire survey in biorisk management guidelines of CWA 15793 was designed to find quality control breaches in lab design, personal, equipment and consumable, quality control measures adopted in lab, waste management, environmental monitoring and customer care. The data was analyzed through frequency distribution statistically by using (SPSS) version 18.0. A non-significant difference was found in all parameters of lab design, personal, equipment and consumable, quality control measures adopted in lab, waste management, environmental monitoring and customer care with an average percentage of 46.6, 57.77, 52.7, 55.5, 54.44, 48.88 and 60, respectively. A non-significant difference among all nine labs were found, with highest average compliance percentage of all parameters are lab 2 (78.13), Lab 3 (70.56), Lab 5 (57.51), Lab 6 (56.37), Lab 4 (55.02), Lab 9 (49.58), Lab 7 (47.76), Lab 1 (41.01) and Lab 8 (36.09). This study shows that in Lahore district veterinary diagnostic labs are not giving proper attention to quality of their system and there is no significant difference between setups of private and public sector laboratories. These results show that most of parameters are between 50 and 80 percent, which needs some work and improvement as per WHO criteria.

Keywords: veterinary lab, quality management system, accreditation, regulatory body, disease identification

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Authors: Ana L. Martins, Luis Orfão

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Healthcare systems have been subject to various research efforts aiming at process improvement under a lean approach. Another perspective, agility, has also been used, though in a lower scale, in order to analyse the ability of different hospital services to adapt to demand uncertainties. Both perspectives have a common denominator, the improvement of effectiveness and efficiency of the services in a healthcare setting context. Mixing the two approached allows, on one hand, to streamline the processes, and on the other hand the required flexibility to deal with demand uncertainty in terms of both volume and variety. The present research aims to analyse the impacts of the combination of both perspectives in the effectiveness and efficiency of an hospital service. The adopted methodology is based on a case study approach applied to the process of the ambulatory surgery service of Hospital de Lamego. Data was collected from direct observations, formal interviews and informal conversations. The analyzed process was selected according to three criteria: relevance of the process to the hospital, presence of human resources, and presence of waste. The customer of the process was identified as well as his perception of value. The process was mapped using flow chart, on a process modeling perspective, as well as through the use of Value Stream Mapping (VSM) and Process Activity Mapping. The Spaghetti Diagram was also used to assess flow intensity. The use of the lean tools enabled the identification of three main types of waste: movement, resource inefficiencies and process inefficiencies. From the use of the lean tools improvement suggestions were produced. The results point out that leagility cannot be applied to the process, but the application of lean and agility in specific areas of the process would bring benefits in both efficiency and effectiveness, and contribute to value creation if improvements are introduced in hospital’s human resources and facilities management.

Keywords: case study, healthcare systems, leagility, lean management

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Authors: Waqas Shafqat Chattha, Muhammad Iqbal, Amir Shakeel

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Transcriptional factors are proteins that play a vital role in regulating the transcription of target genes in different biological processes and are being widely studied in different plant species. In the current era of genomics, plant genomes sequencing has directed to the genome-wide identification, analyses and categorization of diverse transcription factor families and hence provide key insights into their structural as well as functional diversity. The DNA-binding with One Finger (DOF) proteins belongs to C2-C2-type zinc finger protein family. DOF proteins are plant-specific transcription factors implicated in diverse functions including seed maturation and germination, phytohormone signalling, light-mediated gene regulation, cotton-fiber elongation and responses of the plant to biotic as well as abiotic stresses. In this context, a genome-wide in-silico analysis of DOF TF family in diploid cotton species i.e. Gossypium raimondii has enabled us to identify 55 non-redundant genes encoding DOF proteins renamed as GrDofs (Gossypium raimondii Dof). Gene distribution studies have shown that all of the GrDof genes are unevenly distributed across 12 out of 13 G. raimondii chromosomes. The gene structure analysis illustrated that 34 out of 55 GrDof genes are intron-less while remaining 21 genes have a single intron. Protein sequence-based phylogenetic analysis of putative 55 GrDOFs has divided these proteins into 5 major groups with various paralogous gene pairs. Molecular evolutionary studies aided with the conserved domain as well as gene structure analysis suggested that segmental duplications were the principal contributors for the expansion of Dof genes in G. raimondii.

Keywords: diploid cotton , G. raimondii, phylogenetic analysis, transcription factor

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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: Selin Tosun

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The improvements in technology have started to transform the way we live, work, play, and commute in our cities. The emerging smart city understanding has been paving the way for more efficient, more useful, and more profitable cities. Smart sensors, smart lighting, smart waste, water and electricity management, smart transportation and communication systems are introduced to cities at a rapid pace. In today's world, innovation is often correlated with start-up companies and technological pioneers seeking broader economic objectives such as production and competitiveness. The government's position is primarily that of an enabler, with creativity mostly coming from the private sector. The paper argues that to achieve sustainable development, the ways in which smart and sustainable city approaches are being applied to cities need to be redefined. The research aims to address common discussions in the discourse of smart and sustainable cities criticizing the priority of lifestyle sterilization over human-centered sustainable interventions and social innovation strategies. The dichotomy between the fact that smart cities are mostly motivated by the competitive global market and the fact that the delocalization is, in fact, their biggest problem in the way of becoming authentic, sustainable cities is the main challenge that we face today. In other words, the key actors in smart cities have different and somewhat conflicting interests and demands. By reviewing the roles of the public and private actors in smart city making, the paper aspires to reconceptualize the understanding of “smartness” in achieving sustainable development in which the “smartness” is understood as a multi-layered complex phenomenon that can be channeled through different dynamics. The case cities around the world are explored and compared in terms of their technological innovations, governance and policy innovations, public-private stakeholder relationships, and the understanding of the public realm. The study aims to understand the current trends and general dynamics in the field, key issues that are being addressed, the scale that is preferred to reflect upon and the projects that are designed for the particular issues.

Keywords: smart city, sustainable development, technological innovation, social innovation

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Authors: Khan Md. Abdus Subhan, Rabeya Bushra

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Bangladesh has already seen significant growth in Islamic banking and finance, contributing to the rapid expansion of this sector in the global banking and finance industry. The objective of this study is to analyse the Islamic finance and banking industry's ability to contribute to sustainable development in Bangladesh. It aims to assess the current state, potential, and limitations of Islamic banking and finance in the country. Bangladesh has significant growth potential for Islamic banking and finance. However, addressing several challenges is imperative. These challenges include the absence of a well-developed infrastructure for Islamic banking and finance, a lack of a solid legal framework, limited attention from the central bank, the absence of an Islamic capital market, and a shortage of experts in Sharia law as well as public awareness. Bangladesh, a nation characterized by a primarily Muslim populace, has acknowledged the importance of Islamic finance and banking in promoting sustainable development. Islamic banking principles advocate for ethical practices, risk sharing, and the avoidance of interest-based transactions. This article examines the impact of Islamic finance and banking on promoting sustainable development in Bangladesh and emphasizes its capacity to tackle socio-economic difficulties. The Islamic banking sector, as a trailblazer in funding sustainable development, has the potential to play a significant role in facilitating the shift toward a circular economy. According to Shari'ah rules and the Sustainable Development Goals (SDGs), Islamic finance principles will help change the linear economy into a circular one. They will also provide a strong framework and a lot of funding sources. This study aims to offer crucial recommendations and techniques for the successful implementation of Islamic finance institutions in Bangladesh. The study will use quantitative research methodology, collecting data from secondary sources. This research offers a thorough understanding of the reasoning for the payment of Zakat and its socio-economic importance. Furthermore, the study provides significant insights that could assist Bangladeshi policymakers and governments in implementing Islamic financing systems.

Keywords: sustainable development, Islamic fintech, Islamic banking, Bangladesh

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Authors: M. R. Vijayakumar, Sanjay Kumar Singh, Lakshmi, Hithesh Dewangan, Sanjay Singh

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Trans resveratrol (RES) is a natural molecule proved for cancer preventive and therapeutic activities devoid of any potential side effects. However, the therapeutic application of RES in disease management is limited because of its rapid elimination from blood circulation thereby low biological half life in mammals. Therefore, the main objective of this study is to enhance the circulation as well as therapeutic efficacy using PEGylated liposomes. D-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) is applied as steric surface decorating agent to prepare RES liposomes by thin film hydration method. The prepared nanoparticles were evaluated by various state of the art techniques such as dynamic light scattering (DLS) technique for particle size and zeta potential, TEM for shape, differential scanning calorimetry (DSC) for interaction analysis and XRD for crystalline changes of drug. Encapsulation efficiency and invitro drug release were determined by dialysis bag method. Cancer cell viability studies were performed by MTT assay, respectively. Pharmacokinetic studies were performed in sprague dawley rats. The prepared liposomes were found to be spherical in shape. Particle size and zeta potential of prepared formulations varied from 64.5±3.16 to 262.3±7.45 nm and -2.1 to 1.76 mV, respectively. DSC study revealed absence of potential interaction. XRD study revealed presence of amorphous form in liposomes. Entrapment efficiency was found to be 87.45±2.14 % and the drug release was found to be controlled up to 24 hours. Minimized MEC in MTT assay and tremendous enhancement in circulation time of RES PEGylated liposomes than its pristine form revealed that the stearic stabilized PEGylated liposomes can be an alternative tool to commercialize this molecule for chemopreventive and therapeutic applications in cancer.

Keywords: trans resveratrol, cancer nanotechnology, long circulating liposomes, bioavailability enhancement, liposomes for cancer therapy, PEGylated liposomes

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Authors: Hi̇lal Surat

Abstract:

People who want to get rid of stress and intensive working tempo for a while head for recreation operations in order to get rest and have fun. Therefore, planning recreation operation makes contributions to social, physiological, economic and psychological development of an individual and the community in a way that the needs of people meet regularly and constantly. The rapid increase of world population rate makes necessary of benefit from natural or man-made resources in a multiple way. Dams and reservoirs which are built near urban area with the aim of electrical energy conversion and agricultural irrigation are considered as natural area providing various opportunities such as recreation operations. Dams have a great importance regarding to protection and improvement of water resources and coming into service of community. There should be a priority to protect these water resources, which are essential for nature and living organisms. It should be taken into consideration that these water resources are the most important input in the area and have high nature value to make sustainability of recreation effectiveness. The Deriner reservoir that has been built yet near the province of Artvin with natural and cultural properties is considered as an alternative option for meeting the needs of people for sportive and recreation activities and as a potential for planning of water-based recreation activities. Hence, in this study, activities that meet the expectations of people who get benefit from the area considering to natural, cultural and sportive recreation opportunities will be developed. In the first place, planning criteria for some sportive and water-based recreation operations will be defined in order to use the area for recreation and sportive activities and these criteria will be a base for a macro planning work within the holistic perspective of natural, cultural, and economical structure of the area. After this time, necessities of local people and evaluation of reservoir recreational potential will be determined, end then different socio-economic groups according to their in-come, age groups will be chosen and the questionnaire which has already prepared will be done these groups, as a result of these questionnaire recreational activities in water necessities will determine and we are going to develop different suggestion for this reservoir.

Keywords: dam, dam lakes, Deriner, recreation, water based activities

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Authors: Amir Reza Asnafi, Ehsan Tajabadi, Mohsen Hajizeinolabedini

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The purpose of this study is to identify the concept of knowledge flow in central libraries of Tehran universities in by the pattern of American Productivity & Quality Center (APQC). The present study is an applied and descriptive survey in terms of its purpose and the methodology used. In this study, APQC framework was used for data collection. The study population is managers and supervisors of central libraries’ departments of public universities of Tehran belonging to the Ministry of Science, Research and Technology. These libraries include: Central Libraries of Al-Zahra University, Amir Kabir, Tarbiat Modarres, Tehran, Khajeh Nasir Toosi University of Technology, Shahed, Sharif, Shahid Beheshti, Allameh Tabataba'i University, Iran University of Science and Technology. Due to the limited number of members of the community, sampling was not performed and the census was conducted instead. The study of knowledge flow in central libraries of public universities in Tehran showed that in seven dimensions of knowledge flow of APQC, these libraries are far from desirable level and to achieve the ideal point, many activities in the field of knowledge flow need to be made, therefore suggestions were made in this study to reach the desired level. One Sample t Test in this research showed that these libraries are at a poor level in terms of these factors: in the dimensions of creation, identification and use of knowledge at a medium level and in the aspects of knowledge acquisition, review, sharing and access and also Manova test or Multivariable Analyze of Variance proved that there was no significant difference between the dimensions of knowledge flow between these libraries and the status of the knowledge flow in these libraries is at the same level as well. Except for the knowledge creation aspect that is slightly different in this regard that was mentioned before.

Keywords: knowledge flow, knowledge management, APQC, Tehran’s academic university libraries

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Authors: Mariame Taibi, Marouane Aouiji, Rachid Bengueddour

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The Moroccan coastline is particularly rich in algae and constitutes a reserve of species with considerable economic, social and ecological potential. This work focuses on the research and characterization of algae bioactive compounds that can be used in pharmacology or phytopathology. The biochemical composition of the green alga Ulva lactuca (Ulvophyceae) was studied by determining the content of moisture, ash, phenols, flavonoids, total tannins, and chlorophyll. Seven solvents: distilled water, methanol, ethyl acetate, chloroform, benzene, petroleum ether, and hexane, were tested for their effectiveness in recovering chemical compounds. The identification of functional groupings, as well as the bioactive chemical compounds, was determined by FT-IR and GC-MS. The moisture content of the alga was 77%, while the ash content was 15%. Phenol content differed from one solvent studied to another, while chlorophyll a, b, and total chlorophyll were determined at 14%, 9.52%, and 25%, respectively. Carotenoid was present in a considerable amount (8.17%). The experimental results show that methanol is the most effective solvent for recovering bioactive compounds, followed by water. Moreover, the green alga Ulva lactuca is characterized by a high level of total polyphenols (45±3.24 mg GAE/gDM), average levels of total tannins and flavonoids (22.52±8.23 mg CE/gDM, 15.49±0.064 mg QE/gDM) respectively. The results of Fourier transform infrared spectroscopy (FT-IR) confirmed the presence of alcohol/phenol and amide functions in Ulva lactuca. The GC-MS analysis gave precisely the compounds contained in the various extracts, such as phenolic compounds, fatty acids, terpenoids, alcohols, alkanes, hydrocarbons, and steroids. All these results represent only a first step in the search for biologically active natural substances from seaweed. Additional tests are envisaged to confirm the bioactivity of seaweed.

Keywords: algae, Ulva lactuca, phenolic compounds, FTIR, GC-MS

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Authors: Samar Mousa, Galini Mavromatidou, Rebecca Shirley

Abstract:

Surgeons carry out numerous operations in the busy burns and plastic surgery department daily. Writing an accurate operation note with all the essential information is crucial for communication not only within the plastics team but also to the multi-disciplinary team looking after the patient, including other specialties, nurses and GPs. The Royal college of surgeons of England, in its guidelines of good surgical practice, mentioned that the surgeon should ensure that there are clear (preferably typed) operative notes for every procedure. The notes should accompany the patient into recovery and to the ward and should give sufficient detail to enable continuity of care by another doctor. The notes should include the Date and time, Elective/emergency procedure, Names of the operating surgeon and assistant, Name of the theatre anesthetist, Operative procedure carried out, Incision, Operative diagnosis, Operative findings, Any problems/complications, Any extra procedure performed and the reason why it was performed, Details of tissue removed, added or altered, Identification of any prosthesis used, including the serial numbers of prostheses and other implanted materials, Details of closure technique, Anticipated blood loss, Antibiotic prophylaxis (where applicable), DVT prophylaxis (where applicable), Detailed postoperative care instructions and Signature. Fourteen random days were chosen in December 2021 to assess the accuracy of operative notes and post-operative care. A total of 163 operative notes were examined. The average completion rates in all domains were 85.4%. An electronic operative note template was designed to cover all domains mentioned in the Royal College of surgeons' good surgical practice. It is kept in the hospital drive for all surgeons to use.

Keywords: operative notes, plastic surgery, documentation, electronic

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Authors: Moiseenko F. V., Volkov N. M., Zhabina A. S., Stepanova E. O., Kirillov A. V., Myslik A. V., Artemieva E. V., Agranov I. R., Oganesyan A. P., Egorenkov V. V., Abduloeva N. H., Aleksakhina S. Yu., Ivantsov A. O., Kuligina E. S., Imyanitov E. N., Moiseyenko V. M.

Abstract:

Analysis of ctDNA in patients with NSCLC is an emerging biomarker. Multiple research efforts of quantitative or at least qualitative analysis before and during the first periods of treatment with TKI showed the prognostic value of ctDNA clearance. Still, these important results are not incorporated in clinical standards. We evaluated the role of ctDNA in EGFR-mutated NSCLC receiving first-line TKI. Firstly, we analyzed sequential plasma samples from 30 patients that were collected before intake of the first tablet (at baseline) and at 6, 12, 24, 36, and 48 hours after the “starting point.” EGFR-M+ allele was measured by ddPCR. Afterward, we included sequential qualitative analysis of ctDNA with cobas® EGFR Mutation Test v2 from 99 NSCLC patients before the first dose, after 2 and 4 months of treatment, and on progression. Early response analysis showed the decline of EGFR-M+ level in plasma within the first 48 hours of treatment in 11 subjects. All these patients showed objective tumor response. 10 patients showed either elevation of EGFR-M+ plasma concentration (n = 5) or stable content of circulating EGFR-M+ after the start of the therapy (n = 5); only 3 of these patients achieved an objective response (p = 0.026) when compared to the former group). The rapid decline of plasma EGFR-M+ DNA concentration also predicted for longer PFS (13.7 vs. 11.4 months, p = 0.030). Long-term ctDNA monitoring showed clinically significant heterogeneity of EGFR-mutated NSCLC treated with 1st line TKIs in terms of progression-free and overall survival. Patients without detectable ctDNA at baseline (N = 32) possess the best prognosis on the duration of treatment (PFS: 24.07 [16.8-31.3] and OS: 56.2 [21.8-90.7] months). Those who achieve clearance after two months of TKI (N = 42) have indistinguishably good PFS (19.0 [13.7 – 24.2]). Individuals who retain ctDNA after 2 months (N = 25) have the worst prognosis (PFS: 10.3 [7.0 – 13.5], p = 0.000). 9/25 patients did not develop ctDNA clearance at 4 months with no statistical difference in PFS from those without clearance at 2 months. Prognostic heterogeneity of EGFR-mutated NSCLC should be taken into consideration in planning further clinical trials and optimizing the outcomes of patients.

Keywords: NSCLC, EGFR, targeted therapy, ctDNA, prognosis

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