Search results for: small waterbodies

Authors: Maria Areias, Diogo Simões, Ana Figueiredo, Anishur Rahman, Filipa Figueiredo, João Nunes

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It is expected that close to 7 billion people will live in urban areas by 2050. In order to improve the sustainability of the territories and its transition towards circular economy, it’s necessary to understand its metabolism and promote and guide the entrepreneurship answer. The study of a macroeconomic metabolism involves the quantification of the inputs, outputs and storage of energy, water, materials and wastes for an urban region. This quantification and analysis representing one opportunity for the promotion of green entrepreneurship. There are several methods to assess the environmental impacts of an urban territory, such as human and environmental risk assessment (HERA), life cycle assessment (LCA), ecological footprint assessment (EF), material flow analysis (MFA), physical input-output table (PIOT), ecological network analysis (ENA), multicriteria decision analysis (MCDA) among others. However, no consensus exists about which of those assessment methods are best to analyze the sustainability of these complex systems. Taking into account the weaknesses and needs identified, the CiiM - Circular Innovation Inter-Municipality project aims to define an uniform and globally accepted methodology through the integration of various methodologies and dynamic approaches to increase the efficiency of macroeconomic metabolisms and promoting entrepreneurship in a circular economy. The pilot territory considered in CiiM project has a total area of 969,428 ha, comprising a total of 897,256 inhabitants (about 41% of the population of the Center Region). The main economic activities in the pilot territory, which contribute to a gross domestic product of 14.4 billion euros, are: social support activities for the elderly; construction of buildings; road transport of goods, retailing in supermarkets and hypermarkets; mass production of other garments; inpatient health facilities; and the manufacture of other components and accessories for motor vehicles. The region's business network is mostly constituted of micro and small companies (similar to the Central Region of Portugal), with a total of 53,708 companies identified in the CIM Region of Coimbra (39 large companies), 28,146 in the CIM Viseu Dão Lafões (22 large companies) and 24,953 in CIM Beiras and Serra da Estrela (13 large companies). For the construction of the database was taking into account data available at the National Institute of Statistics (INE), General Directorate of Energy and Geology (DGEG), Eurostat, Pordata, Strategy and Planning Office (GEP), Portuguese Environment Agency (APA), Commission for Coordination and Regional Development (CCDR) and Inter-municipal Community (CIM), as well as dedicated databases. In addition to the collection of statistical data, it was necessary to identify and characterize the different stakeholder groups in the pilot territory that are relevant to the different metabolism components under analysis. The CIIM project also adds the potential of a Geographic Information System (GIS) so that it is be possible to obtain geospatial results of the territorial metabolisms (rural and urban) of the pilot region. This platform will be a powerful visualization tool of flows of products/services that occur within the region and will support the stakeholders, improving their circular performance and identifying new business ideas and symbiotic partnerships.

Keywords: circular economy tools, life cycle assessment macroeconomic metabolism, multicriteria decision analysis, decision support tools, circular entrepreneurship, industrial and regional symbiosis

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Authors: Ayla Hoeta

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In a post-colonial Aotearoa New Zealand, solutions by rangatahi (youth) for rangatahi are essential as is civic participation and building economic agency in an increasingly tough economic climate. Upsouth was an online community crowdsourcing platform developed by The Southern Initiative, in collaboration with Itsnoon that provides rangatahi and whānau (family) a safe space to share lived experience, thoughts and ideas about local kaupapa (issues/topics) of importance to them. The target participants were Māori indigenous peoples and Pacifica groups, aged 14 - 21 years. In the Aotearoa New Zealand context, this participant group is not likely to engage in traditional consultation processes despite being an essential constituent in helping shape better local communities, whānau and futures. The Upsouth platform was active for two years from 2018-2019 where it completed 42 callups with 4300+ participants. The web platform collates the ideas, voices, feedback, and content of users around a callup that has been commissioned by a sponsor, such as Auckland Council, Z Energy or Auckland Transport. A callup may be about a pressing challenge in a community such as climate change, a new housing development, homelessness etc. Each callup was funded by the sponsor with Upsouths main point of difference being that participants are given koha (money donation) through digital wallets for their ideas. Depending on the quality of what participants upload, the koha varies between small micropayments and larger payments. This encouraged participants to develop creative and critical thinking - upskilling for future focussed jobs, enterprise and democratic skills while earning pocket money at the same time. Upsouth enables youth-led action and voice, and empowers them to be a part of a reciprocal and creative economy. Rangatahi are encouraged to express themselves culturally, creatively, freely and in a way they are free to choose - for example, spoken word, song, dance, video, drawings, and/or poems. This challenges and changes what is considered acceptable as community engagement feedback by the local government. Many traditional engagement platforms are not as consultative, do not accept diverse types of feedback, nor incentivise this valuable expression of feedback. Upsouth is also empowering for rangatahi, since it allows them the opportunity to express their opinions directly to the government. Upsouth gained national and international recognition for the way it engages with youth: winning the Supreme Award and the Accessibility and Transparency Award at Auckland Council’s 2018 Engagement Awards, becoming a finalist in the 2018 Digital Equity and Accessibility category of International Data Corporation’s Smart City Asia and Pacific Awards. This paper will fully contextualize the challenges of rangatahi and whānau civic engagement in Aotearoa New Zealand and then present a reflective case study of the Upsouth project, with examples from some of the callups. This is intended to form part of the Divided Cities 22 conference New Ground sub-theme as a critical reflection on a design intervention, which was conceived and implemented by the lead author to overcome the post-colonial divisions of Māori, Pacifica and minority ethnic rangatahi in Aotearoa New Zealand.

Keywords: rangatahi, youth empowerment, civic engagement, enabling, relating, digital platform, participation

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Authors: Sajeli A. Begum, Ameer Basha, Kirti Hira, Rukaiyya Khan

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Cyclic dipeptides are simple diketopiperazine derivatives being investigated by several scientists for their biological effects which include anticancer, antimicrobial, haematological, anticonvulsant, immunomodulatory effect, etc. They are potentially active microbial metabolites having been synthesized too, for developing into drug candidates. Cultures of Pseudomonas species have earlier been reported to produce cyclic dipeptides, helping in quorum sensing signals and bacterial–host colonization phenomena during infections, causing cell anti-proliferation and immunosuppression. Fluorescing Pseudomonas species have been identified to secrete lipid derivatives, peptides, pyrroles, phenazines, indoles, aminoacids, pterines, pseudomonic acids and some antibiotics. In the present work, results of investigation on the cyclic dipeptide metabolites secreted by the culture broth of Pseudomonas species as potent pro-inflammatory cytokine inhibitors are discussed. The bacterial strain was isolated from the rhizospheric soil of groundnut crop and identified as Pseudomonas aeruginosa by 16S rDNA sequence (GenBank Accession No. KT625586). Culture broth of this strain was prepared by inoculating into King’s B broth and incubating at 30 ºC for 7 days. The ethyl acetate extract of culture broth was prepared and lyophilized to get a dry residue (EEPA). Lipopolysaccharide (LPS)-induced ELISA assay proved the inhibition of tumor necrosis factor-alpha (TNF-α) secretion in culture supernatant of RAW 264.7 cells by EEPA (IC50 38.8 μg/mL). The effect of oral administration of EEPA on plasma TNF-α level in rats was tested by ELISA kit. The LPS mediated plasma TNF-α level was reduced to 45% with 125 mg/kg dose of EEPA. Isolation of the chemical constituents of EEPA through column chromatography yielded ten cyclic dipeptides, which were characterized using nuclear magnetic resonance and mass spectroscopic techniques. These cyclic dipeptides are biosynthesized in microorganisms by multifunctional assembly of non-ribosomal peptide synthases and cyclic dipeptide synthase. Cyclo (Gly-L-Pro) was found to be more potentially (IC50 value 4.5 μg/mL) inhibiting TNF-α production followed by cyclo (trans-4-hydroxy-L-Pro-L-Phe) (IC50 value 14.2 μg/mL) and the effect was equal to that of standard immunosuppressant drug, prednisolone. Further, the effect was analyzed by determining mRNA expression of TNF-α in LPS-stimulated RAW 264.7 macrophages using quantitative real-time reverse transcription polymerase chain reaction. EEPA and isolated cyclic dipeptides demonstrated diminution of TNF-α mRNA expression levels in a dose-dependent manner under the tested conditions. Also, they were found to control the expression of other pro-inflammatory cytokines like IL-1β and IL-6, when tested through their mRNA expression levels in LPS-stimulated RAW 264.7 macrophages under LPS-stimulated conditions. In addition, significant inhibition effect was found on Nitric oxide production. Further all the compounds exhibited weak toxicity to LPS-induced RAW 264.7 cells. Thus the outcome of the study disclosed the effectiveness of EEPA and the isolated cyclic dipeptides in down-regulating key cytokines involved in pathophysiology of autoimmune diseases.In another study led by the investigators, microbial cyclic dipeptides were found to exhibit excellent antimicrobial effect against Fusarium moniliforme which is an important causative agent of Sorghum grain mold disease. Thus, cyclic dipeptides are emerging small molecular drug candidates for various autoimmune diseases.

Keywords: cyclic dipeptides, cytokines, Fusarium moniliforme, Pseudomonas, TNF-alpha

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Authors: Heather E. Ewart, Keith Jensen, Rebecca N. Cliffe

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Fragmentation and changes in the structural composition of tropical forests – as a result of intensifying anthropogenic disturbance – are increasing pressures on local biodiversity. Species with low dispersal abilities have some of the highest extinction risks in response to environmental change, as even small-scale environmental variation can substantially impact their space use and energetic balance. Understanding the implications of forest disturbance is therefore essential, ultimately allowing for more effective and targeted conservation initiatives. Here, the impact of different levels of forest disturbance on the space use, energetics, movement and behavior of 18 brown-throated sloths (Bradypus variegatus) were assessed in the South Caribbean of Costa Rica. A multi-scale framework was used to measure forest disturbance, including large-scale (landscape-level classifications) and fine-scale (within and surrounding individual home ranges) forest composition. Three landscape-level classifications were identified: primary forests (undisturbed), secondary forests (some disturbance, regenerating) and urban forests (high levels of disturbance and fragmentation). Finer-scale forest composition was determined using measurements of habitat structure and quality within and surrounding individual home ranges for each sloth (home range estimates were calculated using autocorrelated kernel density estimation [AKDE]). Measurements of forest quality included tree connectivity, density, diameter and height, species richness, and percentage of canopy cover. To determine space use, energetics, movement and behavior, six sloths in urban forests, seven sloths in secondary forests and five sloths in primary forests were tracked using a combination of Very High Frequency (VHF) radio transmitters and Global Positioning System (GPS) technology over an average period of 120 days. All sloths were also fitted with micro data-loggers (containing tri-axial accelerometers and pressure loggers) for an average of 30 days to allow for behavior-specific movement analyses (data analysis ongoing for data-loggers and primary forest sloths). Data-loggers included determination of activity budgets, circadian rhythms of activity and energy expenditure (using the vector of the dynamic body acceleration [VeDBA] as a proxy). Analyses to date indicate that home range size significantly increased with the level of forest disturbance. Female sloths inhabiting secondary forests averaged 0.67-hectare home ranges, while female sloths inhabiting urban forests averaged 1.93-hectare home ranges (estimates are represented by median values to account for the individual variation in home range size in sloths). Likewise, home range estimates for male sloths were 2.35 hectares in secondary forests and 4.83 in urban forests. Sloths in urban forests also used nearly double (median = 22.5) the number of trees as sloths in the secondary forest (median = 12). These preliminary data indicate that forest disturbance likely heightens the energetic requirements of sloths, a species already critically limited by low dispersal ability and rates of energy acquisition. Energetic and behavioral analyses from the data-loggers will be considered in the context of fine-scale forest composition measurements (i.e., habitat quality and structure) and are expected to reflect the observed home range and movement constraints. The implications of these results are far-reaching, presenting an opportunity to define a critical index of habitat connectivity for low dispersal species such as sloths.

Keywords: biodiversity conservation, forest disturbance, movement ecology, sloths

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Authors: Alberto Alfano, Sergio D’ambrosio, Darshankumar Parecha, Donatella Cimini, Chiara Schiraldi.

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The main objective of this study regards the setup of an efficient small-scale platform for the conversion of local renewable waste materials, such as whey, into added-value products, thereby reducing environmental impact and costs deriving from the disposal of processing waste products. The buffalo milk whey derived from the cheese-making process, called second cheese whey, is the main by-product of the dairy industry. Whey is the main and most polluting by-product obtained from cheese manufacturing consisting of lactose, lactic acid, proteins, and salts, making whey an added-value product. In Italy, and in particular, in the Campania region, soft cheese production needs a large volume of liquid waste, especially during late spring and summer. This project is part of a circular economy perspective focused on the conversion of potentially polluting and difficult to purify waste into a resource to be exploited, and it embodies the concept of the three “R”: reduce, recycle, and reuse. Special focus was paid to the production of health-promoting biomolecules and biopolymers, which may be exploited in different segments of the food and pharmaceutical industries. These biomolecules may be recovered through appropriate processes and reused in an attempt to obtain added value products. So, ultrafiltration and nanofiltration processes were performed to fractionate bioactive components starting from buffalo milk whey. In this direction, the present study focused on the implementation of a downstream process that converts waste generated from food and food processing industries into added value products with potential applications. Owing to innovative downstream and biotechnological processes, rather than a waste product may be considered a resource to obtain high added value products, such as food supplements (probiotics), cosmeceuticals, biopolymers, and recyclable purified water. Besides targeting gastrointestinal disorders, probiotics such as Lactobacilli have been reported to improve immunomodulation and protection of the host against infections caused by viral and bacterial pathogens. Interestingly, also inactivated microbial (probiotic) cells and their metabolic products, indicated as parabiotic and postbiotics, respectively, have a crucial role and act as mediators in the modulation of the host’s immune function. To boost the production of biomass (both viable and/or heat inactivated cells) and/or the synthesis of growth-related postbiotics, such as EPS, efficient and sustainable fermentation processes are necessary. Based on a “zero-waste” approach, wastes generated from local industries can be recovered and recycled to develop sustainable biotechnological processes to obtain probiotics as well as post and parabiotic, to be tested as bioactive compounds against gastrointestinal disorders. The results have shown it was possible to recover an ultrafiltration retentate with suitable characteristics to be used in skin dehydration, to perform films (i.e., packaging for food industries), or as a wound repair agent and a nanofiltration retentate to recover lactic acid and carbon sources (e.g., lactose, glucose..) used for microbial cultivation. On the side, the last goal is to obtain purified water that can be reused throughout the process. In fact, water reclamation and reuse provide a unique and viable opportunity to augment traditional water supplies, a key issue nowadays.

Keywords: biotech process, downstream process, probiotic growth, from waste to product, buffalo whey

Procedia PDF Downloads 69

Authors: Chusit Apirumanekul, Chayanis Krittasudthacheewa, Ratchapat Ratanavaraha, Yanyong Inmuong

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Rapid economic development in the Lower Mekong region is leading to changes in water quantity and quality. Changes in land- and forest-use, infrastructure development, increasing urbanization, migration patterns and climate risks are increasing demands for water, within various sectors, placing pressure on scarce water resources. Appropriate policies, strategies, and planning are urgently needed for improved water resource management. Over the last decade, Thailand has experienced more frequent and intense drought situations, affecting the level of water storage in reservoirs along with insufficient water allocation for agriculture during the dry season. The Huay Saibat River Basin, one of the well-known water-scarce areas in the northeastern region of Thailand, is experiencing ongoing water scarcity that affects both farming livelihoods and household consumption. Drought management in Thailand mainly focuses on emergency responses, rather than advance preparation and mitigation for long-term solutions. Despite many efforts from local authorities to mitigate the drought situation, there is yet no long-term comprehensive water management strategy, that integrates climate risks alongside other uncertainties. This paper assesses the application in the Huay Saibat River Basin, of the Robust Decision Support framework, to explore the feasibility of multiple drought management policies; including a shift in cropping season, in crop changes, in infrastructural operations and in the use of groundwater, under a wide range of uncertainties, including climate and land-use change. A series of consultative meetings were organized with relevant agencies and experts at the local level, to understand and explore plausible water resources strategies and identify thresholds to evaluate the performance of those strategies. Three different climate conditions were identified (dry, normal and wet). Other non-climatic factors influencing water allocation were further identified, including changes from sugarcane to rubber, delaying rice planting, increasing natural retention storage and using groundwater to supply demands for household consumption and small-scale gardening. Water allocation and water use in various sectors, such as in agriculture, domestic, industry and the environment, were estimated by utilising the Water Evaluation And Planning (WEAP) system, under various scenarios developed from the combination of climatic and non-climatic factors mentioned earlier. Water coverage (i.e. percentage of water demand being successfully supplied) was defined as a threshold for water resource strategy assessment. Thresholds for different sectors (agriculture, domestic, industry, and environment) were specified during multi-stakeholder engagements. Plausible water strategies (e.g. increasing natural retention storage, change of crop type and use of groundwater as an alternative source) were evaluated based on specified thresholds in 4 sectors (agriculture, domestic, industry, and environment) under 3 climate conditions. 'Business as usual' was evaluated for comparison. The strategies considered robust, emerge when performance is assessed as successful, under a wide range of uncertainties across the river basin. Without adopting any strategy, the water scarcity situation is likely to escalate in the future. Among the strategies identified, the use of groundwater as an alternative source was considered a potential option in combating water scarcity for the basin. Further studies are needed to explore the feasibility for groundwater use as a potential sustainable source.

Keywords: climate change, robust decision support, scenarios, water resources management

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Authors: Georgina Cherry, Taranpreet Rai, Luke Boyden, Sitira Williams, Andrea Wright, Richard Brown, Viva Chu, Alasdair Cook, Kevin Wells

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Estimating population-level burden, abilities of pet-parents to identify disease and demand for veterinary services worldwide is challenging. The purpose of this study is to compare a feline pruritus survey with social media listening (SML) data discussing this condition. Surveys are expensive and labour intensive to analyse, but SML data is freeform and requires careful filtering for relevancy. This study considers data from a survey of owner-observed symptoms of 156 pruritic cats conducted using Pet Parade® and SML posts collected through web-scraping to gain insights into the characterisation and management of feline pruritus. SML posts meeting a feline body area, behaviour and symptom were captured and reviewed for relevance representing 1299 public posts collected from 2021 to 2023. The survey involved 1067 pet-parents who reported on pruritic symptoms in their cats. Among the observed cats, approximately 18.37% (n=196) exhibited at least one symptom. The most frequently reported symptoms were hair loss (9.2%), bald spots (7.3%) and infection, crusting, scaling, redness, scabbing, scaling, or bumpy skin (8.2%). Notably, bald spots were the primary symptom reported for short-haired cats, while other symptoms were more prevalent in medium and long-haired cats. Affected body areas, according to pet-parents, were primarily the head, face, chin, neck (27%), and the top of the body, along the spine (22%). 35% of all cats displayed excessive behaviours consistent with pruritic skin disease. Interestingly, 27% of these cats were perceived as non-symptomatic by their owners, suggesting an under-identification of itch-related signs. Furthermore, a significant proportion of symptomatic cats did not receive any skin disease medication, whether prescribed or over the counter (n=41). These findings indicate a higher incidence of pruritic skin disease in cats than recognized by pet owners, potentially leading to a lack of medical intervention for clinically symptomatic cases. The comparison between the survey and social media listening data revealed bald spots were reported in similar proportions in both datasets (25% in the survey and 28% in SML). Infection, crusting, scaling, redness, scabbing, scaling, or bumpy skin accounted for 31% of symptoms in the survey, whereas it represented 53% of relevant SML posts (excluding bumpy skin). Abnormal licking or chewing behaviours were mentioned by pet-parents in 40% of SML posts compared to 38% in the survey. The consistency in the findings of these two disparate data sources, including a complete overlap in affected body areas for the top 80% of social media listening posts, indicates minimal biases in each method, as significant biases would likely yield divergent results. Therefore, the strong agreement across pruritic symptoms, affected body areas, and reported behaviours enhances our confidence in the reliability of the findings. Moreover, the small differences identified between the datasets underscore the valuable insights that arise from utilising multiple data sources. These variations provide additional depth in characterising and managing feline pruritus, allowing for more comprehensive understanding of the condition. By combining survey data and social media listening, researchers can obtain a nuanced perspective and capture a wider range of experiences and perspectives, supporting informed decision-making in veterinary practice.

Keywords: social media listening, feline pruritus, surveys, felines, cats, pet owners

Procedia PDF Downloads 127

Authors: M. C. O. Ezeibe, F. I. O. Ezeibe

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Reasons viral diseases (including AI, HIV/AIDS, and COVID-19), tumors (including Cancers and Prostrate enlargement), and antimicrobial-resistant infections (AMR) are difficult to cure are features of the pathogens which normal cells do not have or need (biomedical markers) have not been identified; medicines that can counter the markers have not been invented; strategies and mechanisms for their treatments have not been developed. When cells become abnormal, they acquire negative electrical charges, and viruses are either positively charged or negatively charged, while normal cells remain neutral (without electrical charges). So, opposite charges' electrostatic attraction is a treatment mechanism for viral diseases and tumors. Medicines that have positive electrical charges would mop abnormal (infected and tumor) cells and DNA viruses (negatively charged), while negatively charged medicines would mop RNA viruses (positively charged). Molecules of Aluminum-magnesium silicate [AMS: Al₂Mg₃ (SiO₄)₃], an approved medicine and pharmaceutical stabilizing agent, consist of nanoparticles which have both positive electrically charged ends and negative electrically charged ends. The very small size (0.96 nm) of the nanoparticles allows them to reach all cells in every organ. By stabilizing antimicrobials, AMS reduces the rate at which the body metabolizes them so that they remain at high concentrations for extended periods. When drugs remain at high concentrations for longer periods, their efficacies improve. Again, nanoparticles enhance the delivery of medicines to effect targets. Both remaining at high concentrations for longer periods and better delivery to effect targets improve efficacy and make lower doses achieve desired effects so that side effects of medicines are reduced to allow the immunity of patients to be enhanced. Silicates also enhance the immune responses of treated patients. Improving antimicrobial efficacies and enhancing patients` immunity terminate infections so that none remains that could develop resistance. Some countries do not have natural deposits of AMS, but they may have Aluminum silicate (AS: Al₄ (SiO₄)₃) and Magnesium silicate (MS: Mg₂SiO₄), which are also approved medicines. So, AS and MS were used to formulate an AMS-brand, named Medicinal synthetic AMS {Al₄ (SiO₄)₃ + 3Mg₂SiO₄ → 2Al₂Mg₃ (SiO₄)₃}. To overcome the challenge of AMS, AS, and MS being un-absorbable, Dextrose monohydrate is incorporated in MSAMS-formulations for the simple sugar to convey the electrically charged nanoparticles into blood circulation by the principle of active transport so that MSAMS-antimicrobial formulations function systemically. In vitro, MSAMS reduced (P≤0.05) titers of viruses, including Avian influenza virus and HIV. When used to treat virus-infected animals, it cured Newcastle disease and Infectious bursa disease of chickens, Parvovirus disease of dogs, and Peste des petits ruminants disease of sheep and goats. A number of HIV/AIDS patients treated with it have been reported to become HIV-negative (antibody and antigen). COVID-19 patients are also reported to recover and test virus negative when treated with MSAMS. PSA titers of prostate cancer/enlargement patients normalize (≤4) following treatment with MSAMS. MSAMS has also potentiated ampicillin trihydrate, sulfadimidin, cotrimoxazole, piparazine citrate and chloroquine phosphate to achieve ≥ 95 % infection-load reductions (AMR-prevention). At 75 % of doses of ampicillin, cotrimoxazole, and streptomycin, supporting MSAMS-formulations' treatments with antioxidants led to the termination of even already resistant infections.

Keywords: electrical charges, viruses, abnormal cells, aluminum-magnesium silicate

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Authors: Kalaumari Mayoral-Peña, Ana I. Montejano-Montelongo, Josué Reyes-Muñoz, Gonzalo A. Ortiz-Mancilla, Mayrin Rodríguez-Cruz, Víctor Hernández-Villalobos, Jesús A. Guzmán-López, Santiago García-Jacobo, Iván Licona-Vázquez, Grisel Fierros-Romero, Rosario Flores-Vallejo

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The group B-lactamic antibiotics include some of the most frequently used small drug molecules against bacterial infections. Nevertheless, an alarming decrease in their efficacy has been reported due to the emergence of antibiotic-resistant bacteria. Infections caused by bacteria expressing extended Spectrum B-lactamases (ESBLs) are difficult to treat and account for higher morbidity and mortality rates, delayed recovery, and high economic burden. According to the Global Report on Antimicrobial Resistance Surveillance, it is estimated that mortality due to resistant bacteria will ascend to 10 million cases per year worldwide. These facts highlight the importance of developing low-cost and readily accessible detection methods of drug-resistant ESBLs bacteria to prevent their spread and promote accurate and fast diagnosis. Bacterial detection is commonly done using molecular diagnostic techniques, where PCR stands out for its high performance. However, this technique requires specialized equipment not available everywhere, is time-consuming, and has a high cost. Loop-Mediated Isothermal Amplification (LAMP) is an alternative technique that works at a constant temperature, significantly decreasing the equipment cost. It yields double-stranded DNA of several lengths with repetitions of the target DNA sequence as a product. Although positive and negative results from LAMP can be discriminated by colorimetry, fluorescence, and turbidity, there is still a large room for improvement in the point-of-care implementation. DNA origami is a technique that allows the formation of 3D nanometric structures by folding a large single-stranded DNA (scaffold) into a determined shape with the help of short DNA sequences (staples), which hybridize with the scaffold. This research aimed to generate DNA origami structures using LAMP products as scaffolds to improve the sensitivity to detect ESBLs in point-of-care diagnosis. For this study, the coding sequence of the CTM-X-15 ESBL of E. coli was used to generate the LAMP products. The set of LAMP primers were designed using PrimerExplorerV5. As a result, a target sequence of 200 nucleotides from CTM-X-15 ESBL was obtained. Afterward, eight different DNA origami structures were designed using the target sequence in the SDCadnano and analyzed with CanDo to evaluate the stability of the 3D structures. The designs were constructed minimizing the total number of staples to reduce costs and complexity for point-of-care applications. After analyzing the DNA origami designs, two structures were selected. The first one was a zig-zag flat structure, while the second one was a wall-like shape. Given the sequence repetitions in the scaffold sequence, both were able to be assembled with only 6 different staples each one, ranging between 18 to 80 nucleotides. Simulations of both structures were performed using scaffolds of different sizes yielding stable structures in all the cases. The generation of the LAMP products were tested by colorimetry and electrophoresis. The formation of the DNA structures was analyzed using electrophoresis and colorimetry. The modeling of novel detection methods through bioinformatics tools allows reliable control and prediction of results. To our knowledge, this is the first study that uses LAMP products and DNA-origami in combination to delect ESBL-producing bacterial strains, which represent a promising methodology for diagnosis in the point-of-care.

Keywords: beta-lactamases, antibiotic resistance, DNA origami, isothermal amplification, LAMP technique, molecular diagnosis

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Authors: Sofia Horjales, Florencia Palma

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Our society is currently experiencing a profound transformation, demanding a proactive response from governmental bodies and higher education institutions to empower the next generation as catalysts for change. Environmental sustainability is rooted in the critical need to maintain the equilibrium and integrity of natural ecosystems, ensuring the preservation of precious natural resources and biodiversity for the benefit of both present and future generations. It is an essential cornerstone of sustainable development, complementing social and economic sustainability. In this evolving landscape, active methodologies take a central role, aligning perfectly with the principles of the 2030 Agenda for Sustainable Development and emerging as a pivotal element of teacher education. The emphasis on active learning methods has been driven by the urgent need to nurture sustainability and instill social responsibility in our future leaders. The Universidad Tecnológica of Uruguay (UTEC) is a public, technologically-oriented institution established in 2012. UTEC is dedicated to decentralization, expanding access to higher education throughout Uruguay, and promoting inclusive social development. Operating through Regional Technological Institutes (ITRs) and associated centers spread across the country, UTEC faces the challenge of remote student populations. To address this, UTEC utilizes e-learning for equal opportunities, self-regulated learning, and digital skills development, enhancing communication among students, teachers, and peers through virtual classrooms. The Interdisciplinary Continuing Education Program is part of the Innovation and Entrepreneurship Department of UTEC. The main goal is to strengthen innovation skills through a transversal and multidisciplinary approach. Within this Program, we have developed a Case of Study and Project-Based Learning Virtual Course designed for university students and open to the broader UTEC community. The primary aim of this course is to establish a strong foundation for comprehending and addressing environmental sustainability issues from an interdisciplinary perspective. Upon completing the course, we expect students not only to understand the intricate interactions between social and ecosystem environments but also to utilize their knowledge and innovation skills to develop projects that offer enhancements or solutions to real-world challenges. Our course design centers on innovative learning experiences, rooted in active methodologies. We explore the intersection of these methods with sustainability and social responsibility in the education of university students. A paramount focus lies in gathering student feedback, empowering them to autonomously generate ideas with guidance from instructors, and even defining their own project topics. This approach underscores that when students are genuinely engaged in subjects of their choice, they not only acquire the necessary knowledge and skills but also develop essential attributes like effective communication, critical thinking, and problem-solving abilities. These qualities will benefit them throughout their lifelong learning journey. We are convinced that education serves as the conduit to merge knowledge and cultivate interdisciplinary collaboration, igniting awareness and instigating action for environmental sustainability. While systemic changes are undoubtedly essential for society and the economy, we are making significant progress by shaping perspectives and sparking small, everyday actions within the UTEC community. This approach empowers our students to become engaged global citizens, actively contributing to the creation of a more sustainable future.

Keywords: active learning, environmental education, project-based learning, soft skills development

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Authors: Cory B. Portner, Julie A. Grauert, Lisa M. Stromme, Shelby D. Anderson, Franji H. Mayes

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Introduction: WASHINGTON state in the Pacific Northwest of the United States is internationally known for its technology industry, fisheries, agriculture, and vistas. On January 21, 2020, Washington state also became known as the first state with a confirmed COVID-19 case in the United States, thrusting the state into the international spotlight as the world came to grips with the global threat of this disease presented. Tourism is Washington state’s fourth-largest industry. Tourism to the state generates over 1.8 billion dollars (USD) in local and state tax revenue and employs over 180,000 people. Communicating with residents, stakeholders, and visitors on the status of disease activity, prevention measures, and response updates was vital to stopping the pandemic and increasing compliance and awareness. Significance: In order to communicate vital public health updates, guidance implementation, and safety measures to the public, the Washington State Department of Health established routine live virtual media briefings to reach audiences via social media, internet television, and broadcast television. Through close partnership with regional broadcast news stations and the state public affairs news network, the Washington State Department of Health hosted 95 media briefings from January 2020 through September 2022 and continues to regularly host live virtual media briefings to accommodate the needs of the public and media. Methods: Our methods quickly evolved from hosting briefings in the cement closet of a military base to being able to produce and stream the briefings live from any home-office location. The content was tailored to the hot topic of the day and to the reporter's questions and needs. Virtual media briefings hosted through inexpensive or free platforms online are extremely cost-effective: the only mandatory components are WiFi, a laptop, and a monitor. There is no longer a need for a fancy studio or expensive production software to achieve the goal of communicating credible, reliable information promptly. With minimal investment and a small learning curve, facilitators and panelists are able to host highly produced and engaging media availabilities from their living rooms. Results: The briefings quickly developed a reputation as the best source for local and national journalists to get the latest and most factually accurate information about the pandemic. In the height of the COVID-19 response, 135 unique media outlets logged on to participate in the briefing. The briefings typically featured 4-5 panelists, with as many as 9 experts in attendance to provide information and respond to media questions. Preparation was always a priority: Public Affairs staff for the Washington State Department of Health produced over 170 presenter remarks, including guidance on talking points for 63 expert guest panelists. Implication For Practice: Information is today’s most valuable currency. The ability to disseminate correct information urgently and on a wide scale is the most effective tool in crisis communication. Due to our role as the first state with a confirmed COVID-19 case, we were forced to develop the most accurate and effective way to get life-saving information to the public. The cost-effective, web-based methods we developed can be applied in any crisis to educate and protect communities under threat, ultimately saving lives from a laptop.

Keywords: crisis communications, public relations, media management, news media

Procedia PDF Downloads 184

Authors: Denis Jordan, Daniel Golkowski, Mathias Lukas, Katharina Merz, Caroline Mlynarcik, Max Maurer, Valentin Riedl, Stefan Foerster, Eberhard F. Kochs, Andreas Bender, Ruediger Ilg

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Introduction: So far, clinical assessments that rely on behavioral responses to differentiate coma states or even predict outcome in coma patients are unreliable, e.g. because of some patients’ motor disabilities. The present study was aimed to provide prognosis in coma patients using markers from electroencephalogram (EEG), blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) and [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET). Unsuperwised principal component analysis (PCA) was used for multimodal integration of markers. Methods: Approved by the local ethics committee of the Technical University of Munich (Germany) 20 patients (aged 18-89) with severe brain damage were acquired through intensive care units at the Klinikum rechts der Isar in Munich and at the Therapiezentrum Burgau (Germany). At the day of EEG/fMRI/PET measurement (date I) patients (<3.5 month in coma) were grouped in the minimal conscious state (MCS) or vegetative state (VS) on the basis of their clinical presentation (coma recovery scale-revised, CRS-R). Follow-up assessment (date II) was also based on CRS-R in a period of 8 to 24 month after date I. At date I, 63 channel EEG (Brain Products, Gilching, Germany) was recorded outside the scanner, and subsequently simultaneous FDG-PET/fMRI was acquired on an integrated Siemens Biograph mMR 3T scanner (Siemens Healthineers, Erlangen Germany). Power spectral densities, permutation entropy (PE) and symbolic transfer entropy (STE) were calculated in/between frontal, temporal, parietal and occipital EEG channels. PE and STE are based on symbolic time series analysis and were already introduced as robust markers separating wakefulness from unconsciousness in EEG during general anesthesia. While PE quantifies the regularity structure of the neighboring order of signal values (a surrogate of cortical information processing), STE reflects information transfer between two signals (a surrogate of directed connectivity in cortical networks). fMRI was carried out using SPM12 (Wellcome Trust Center for Neuroimaging, University of London, UK). Functional images were realigned, segmented, normalized and smoothed. PET was acquired for 45 minutes in list-mode. For absolute quantification of brain’s glucose consumption rate in FDG-PET, kinetic modelling was performed with Patlak’s plot method. BOLD signal intensity in fMRI and glucose uptake in PET was calculated in 8 distinct cortical areas. PCA was performed over all markers from EEG/fMRI/PET. Prognosis (persistent VS and deceased patients vs. recovery to MCS/awake from date I to date II) was evaluated using the area under the curve (AUC) including bootstrap confidence intervals (CI, *: p<0.05). Results: Prognosis was reliably indicated by the first component of PCA (AUC=0.99*, CI=0.92-1.00) showing a higher AUC when compared to the best single markers (EEG: AUC<0.96*, fMRI: AUC<0.86*, PET: AUC<0.60). CRS-R did not show prediction (AUC=0.51, CI=0.29-0.78). Conclusion: In a multimodal analysis of EEG/fMRI/PET in coma patients, PCA lead to a reliable prognosis. The impact of this result is evident, as clinical estimates of prognosis are inapt at time and could be supported by quantitative biomarkers from EEG, fMRI and PET. Due to the small sample size, further investigations are required, in particular allowing superwised learning instead of the basic approach of unsuperwised PCA.

Keywords: coma states and prognosis, electroencephalogram, entropy, functional magnetic resonance imaging, machine learning, positron emission tomography, principal component analysis

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Authors: S. Fadda, M. Fiori, C. Matzuzzi

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Mineralized formations in the bottom sediments of a Miocene transgression have been discovered in Sardinia. The mineral assemblage consists of copper sulphides and oxidates suggesting fluctuations of redox conditions in neutral to high-pH restricted shallow-water coastal basins. Azurite/malachite has been observed as authigenic and occurs as loose spheroidal crystalline particles associated with the transitional-littoral horizon forming the bottom of the marine transgression. Many field observations are consistent with a supergenic circulation of metals involving terrestrial groundwater-seawater mixing. Both clastic materials and metals come from Tertiary volcanic edifices while the main precipitating anions, carbonates, and sulphides species are of both continental and marine origin. Formation of Cu carbonates as a supergene secondary 'oxide' assemblage, does not agree with field evidences, petrographic observations along with textural evidences in the host-rock types. Samples were collected along the sedimentary sequence for different analyses: the majority of elements were determined by X-ray fluorescence and plasma-atomic emission spectroscopy. Mineral identification was obtained by X-ray diffractometry and scanning electron microprobe. Thin sections of the samples were examined in microscopy while porosity measurements were made using a mercury intrusion porosimeter. Cu-carbonates deposited at a temperature below 100 C° which is consistent with the clay minerals in the matrix of the host rock dominated by illite and montmorillonite. Azurite nodules grew during the early diagenetic stage through reaction of cupriferous solutions with CO₂ imported from the overlying groundwater and circulating through the sandstones during shallow burial. Decomposition of organic matter in the bottom anoxic waters released additional carbon dioxide to pore fluids for azurite stability. In this manner localized reducing environments were also generated in which Cu was fixed as Cu-sulphide and sulphosalts. Microscopic examinations of textural features of azurite nodules give evidence of primary malachite/azurite deposition rather than supergene oxidation in place of primary sulfides. Photomicrographs show nuclei of azurite and malachite surrounded by newly formed microcrystalline carbonates which constitute the matrix. The typical pleochroism of crystals can be observed also when this mineral fills microscopic fissures or cracks. Sedimentological evidence of transgression and regression indicates that the pore water would have been a variable mixture of marine water and groundwaters with a possible meteoric component in an alternatively exposed and subaqueous environment owing to water-level fluctuation. Salinity data of the pore fluids, assessed at random intervals along the mineralised strata confirmed the values between about 7000 and 30,000 ppm measured in coeval sediments at the base of Miocene falling in the range of a more or less diluted sea water. This suggests a variation in mean pore-fluids pH between 5.5 and 8.5, compatible with the oxidized and reduced mineral paragenesis described in this work. The results of stable isotopes studies reflect the marine transgressive-regressive cyclicity of events and are compatibile with carbon derivation from sea water. During the last oxidative stage of diagenesis, under surface conditions of higher activity of H₂O and O₂, CO₂ partial pressure decreased, and malachite becomes the stable Cu mineral. The potential for these small but high grade deposits does exist.

Keywords: sedimentary, Cu-carbonates, authigenic, tertiary, Sardinia

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Authors: Isabelle Barrett

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Natural watercourses provide a range of vital ecosystem services, notably freshwater provision. They also offer highly heterogeneous habitat which supports an extreme diversity of aquatic life. Exploitation of rivers, changing land use and flood prevention measures have led to habitat degradation and subsequent biodiversity loss; indeed, freshwater species currently face a disproportionate rate of extinction compared to their terrestrial and marine counterparts. Large woody debris (LWD) encompasses the trees, large branches and logs which fall into watercourses, and is responsible for important habitat characteristics. Historically, natural LWD has been removed from streams under the assumption that it is not aesthetically pleasing and is thus ecologically unfavourable, despite extensive evidence contradicting this. Restoration efforts aim to replace lost LWD in order to reinstate habitat heterogeneity. This paper aims to assess the current state of such restoration schemes for improving fluvial ecological health in the UK. A detailed review of the scientific literature was conducted alongside a meta-analysis of 25 UK-based projects involving LWD restoration. Projects were chosen for which sufficient information was attainable for analysis, covering a broad range of budgets and scales. The most effective strategies for river restoration encompass ecological success, stakeholder engagement and scientific advancement, however few projects surveyed showed sensitivity to all three; for example, only 32% of projects stated biological aims. Focus tended to be on stakeholder engagement and public approval, since this is often a key funding driver. Consequently, there is a tendency to focus on the aesthetic outcomes of a project, however physical habitat restoration does not necessarily lead to direct biodiversity increases. This highlights the significance of rivers as highly heterogeneous environments with multiple interlinked processes, and emphasises a need for a stronger scientific presence in project planning. Poor scientific rigour means monitoring is often lacking, with varying, if any, definitions of success which are rarely pre-determined. A tendency to overlook negative or neutral results was apparent, with unjustified focus often put on qualitative results. The temporal scale of monitoring is typically inadequate to facilitate scientific conclusions, with only 20% of projects surveyed reporting any pre-restoration monitoring. Furthermore, monitoring is often limited to a few variables, with biotic monitoring often fish-focussed. Due to their longer life cycles and dispersal capability, fish are usually poor indicators of environmental change, making it difficult to attribute any changes in ecological health to restoration efforts. Although the potential impact of LWD restoration may be positive, this method of restoration could simply be making short-term, small-scale improvements; without addressing the underlying symptoms of degradation, for example water quality, the issue cannot be fully resolved. Promotion of standardised monitoring for LWD projects could help establish a deeper understanding of the ecology surrounding the practice, supporting movement towards adaptive management in which scientific evidence feeds back to practitioners, enabling the design of more efficient projects with greater ecological success. By highlighting LWD, this study hopes to address the difficulties faced within river management, and emphasise the need for a more holistic international and inter-institutional approach to tackling problems associated with degradation.

Keywords: biological monitoring, ecological health, large woody debris, river management, river restoration

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Authors: Liane J. Ioannou, Jonathan Serpell, Cino Bendinelli, David Walters, Jenny Gough, Dean Lisewski, Win Meyer-Rochow, Julie Miller, Duncan Topliss, Bill Fleming, Stephen Farrell, Andrew Kiu, James Kollias, Mark Sywak, Adam Aniss, Linda Fenton, Danielle Ghusn, Simon Harper, Aleksandra Popadich, Kate Stringer, David Watters, Susannah Ahern

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BACKGROUND: There are significant variations in the management, treatment and outcomes of thyroid cancer, particularly in the role of: diagnostic investigation and pre-treatment scanning; optimal extent of surgery (total or hemi-thyroidectomy); use of active surveillance for small low-risk cancers; central lymph node dissections (therapeutic or prophylactic); outcomes following surgery (e.g. recurrent laryngeal nerve palsy, hypocalcaemia, hypoparathyroidism); post-surgical hormone, calcium and vitamin D therapy; and provision and dosage of radioactive iodine treatment. A proven strategy to reduce variations in the outcome and to improve survival is to measure and compare it using high-quality clinical registry data. Clinical registries provide the most effective means of collecting high-quality data and are a tool for quality improvement. Where they have been introduced at a state or national level, registries have become one of the most clinically valued tools for quality improvement. To benchmark clinical care, clinical quality registries require systematic measurement at predefined intervals and the capacity to report back information to participating clinical units. OBJECTIVE: The aim of this study was to develop a core set clinical indicators that enable measurement and reporting of quality of care for patients with thyroid cancer. We hypothesise that measuring clinical quality indicators, developed to identify differences in quality of care across sites, will reduce variation and improve patient outcomes and survival, thereby lessening costs and healthcare burden to the Australian community. METHOD: Preparatory work and scoping was conducted to identify existing high quality, clinical guidelines and best practice for thyroid cancer both nationally and internationally, as well as relevant literature. A bi-national panel was invited to participate in a modified Delphi process. Panelists were asked to rate each proposed indicator on a Likert scale of 1–9 in a three-round iterative process. RESULTS: A total of 236 potential quality indicators were identified. One hundred and ninety-two indicators were removed to reflect the data capture by the Australian and New Zealand Thyroid Cancer Registry (ANZTCR) (from diagnosis to 90-days post-surgery). The remaining 44 indicators were presented to the panelists for voting. A further 21 indicators were later added by the panelists bringing the total potential quality indicators to 65. Of these, 21 were considered the most important and feasible indicators to measure quality of care in thyroid cancer, of which 12 were recommended for inclusion in the final set. The consensus indicator set spans the spectrum of care, including: preoperative; surgery; surgical complications; staging and post-surgical treatment planning; and post-surgical treatment. CONCLUSIONS: This study provides a core set of quality indicators to measure quality of care in thyroid cancer. This indicator set can be applied as a tool for internal quality improvement, comparative quality reporting, public reporting and research. Inclusion of these quality indicators into monitoring databases such as clinical quality registries will enable opportunities for benchmarking and feedback on best practice care to clinicians involved in the management of thyroid cancer.

Keywords: clinical registry, Delphi survey, quality indicators, quality of care

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Authors: Rajwanlop Kumpoopong, Sukit Yindeesuk, Pornchai Silarom

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On May 5, 2014, an earthquake of magnitude 6.3 Richter hit the Northern part of Thailand. The epicenter was in Phan District, Chiang Rai Province. This earthquake or the so-called 2014-Chiang Rai Earthquake is the strongest ground shaking that Thailand has ever been experienced in her modern history. The 2014-Chiang Rai Earthquake confirms the geological evidence, which has previously been ignored by most engineers, that earthquakes of considerable magnitudes 6 to 7 Richter can occurr within the country. This promptly stimulates authorized agencies to pay more attention at the safety of their assets and promotes the comprehensive review of seismic resistance design of their building structures. The focus of this paper is to summarize the damages of highway bridges as a result of the 2014-Chiang Rai ground shaking, the remedy actions, and the research needs. The 2014-Chiang Rai Earthquake caused considerable damages to nearby structures such as houses, schools, and temples. The ground shaking, however, caused damage to only one highway bridge, Mae Laos Bridge, located several kilometers away from the epicenter. The damage of Mae Laos Bridge was in the form of concrete spalling caused by pounding of cap beam on the deck structure. The damage occurred only at the end or abutment span. The damage caused by pounding is not a surprise, but the pounding by only one bridge requires further investigation and discussion. Mae Laos Bridge is a river crossing bridge with relatively large approach structure. In as much, the approach structure is confined by strong retaining walls. This results in a rigid-like approach structure which vibrates at the acceleration approximately equal to the ground acceleration during the earthquake and exerts a huge force to the abutment causing the pounding of cap beam on the deck structure. Other bridges nearby have relatively small approach structures, and therefore have no capability to generate pounding. The effect of mass of the approach structure on pounding of cap beam on the deck structure is also evident by the damage of one pedestrian bridge in front of Thanthong Wittaya School located 50 meters from Mae Laos Bridge. The width of the approach stair of this bridge is wider than the typical one to accommodate the stream of students during pre- and post-school times. This results in a relatively large mass of the approach stair which in turn exerts a huge force to the pier causing pounding of cap beam on the deck structure during ground shaking. No sign of pounding was observed for a typical pedestrian bridge located at another end of Mae Laos Bridge. Although pounding of cap beam on the deck structure of the above mentioned bridges does not cause serious damage to bridge structure, this incident promotes the comprehensive review of seismic resistance design of highway bridges in Thailand. Given a proper mass and confinement of the approach structure, the pounding of cap beam on the deck structure can be easily excited even at the low to moderate ground shaking. In as much, if the ground shaking becomes stronger, the pounding is certainly more powerful. This may cause the deck structure to be unseated and fall off in the case of unrestrained bridge. For the bridge with restrainer between cap beam and the deck structure, the restrainer may prevent the deck structure from falling off. However, preventing free movement of the pier by the restrainer may damage the pier itself. Most highway bridges in Thailand have dowel bars embedded connecting cap beam and the deck structure. The purpose of the existence of dowel bars is, however, not intended for any seismic resistance. Their ability to prevent the deck structure from unseating and their effect on the potential damage of the pier should be evaluated. In response to this expected situation, Thailand Department of Highways (DOH) has set up a team to revise the standard practices for the seismic resistance design of highway bridges in Thailand. In addition, DOH has also funded the research project 'Seismic Resistance Evaluation of Pre- and Post-Design Modifications of DOH’s Bridges' with the scope of full-scale tests of single span bridges under reversed cyclic static loadings for both longitudinal and transverse directions and computer simulations to evaluate the seismic performance of the existing bridges and the design modification bridges. The research is expected to start in October, 2015.

Keywords: earthquake, highway bridge, Thailand, damage, pounding, seismic resistance

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Authors: Aastha Arora, Vikas Bhuria, Saurabh Singh, Uma Pathak, Shweta Mathur, Puja P. Hazari, Rajat Sandhir, Ravi Soni, Anant N. Bhatt, Bilikere S. Dwarakanath

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Radiotherapy is an effective curative and palliative option for patients with thoracic malignancies. However, lung injury, comprising of pneumonitis and fibrosis, remains a significant clin¬ical complication of thoracic radiation, thus making it a dose-limiting factor. Also, injury to the lung is often reported as part of multi-organ failure in victims of accidental radiation exposures. Radiation induced inflammatory response in the lung, characterized by leukocyte infiltration and vascular changes, is an important contributing factor for the injury. Therefore, countermeasure agents to attenuate radiation induced inflammatory response are considered as an important approach to prevent chronic lung damage. Although Amifostine, the widely used, FDA approved radio-protector, has been found to reduce the radiation induced pneumonitis during radiation therapy of non-small cell lung carcinoma, its application during mass and field exposure is limited due to associated toxicity and ineffectiveness with the oral administration. The amifostine analogue (DRDE-30) overcomes this limitation as it is orally effective in reducing the mortality of whole body irradiated mice. The current study was undertaken to investigate the potential of DRDE-30 to ameliorate radiation induced lung damage. DRDE-30 was administered intra-peritoneally, 30 minutes prior to 13.5 Gy thoracic (60Co-gamma) radiation in C57BL/6 mice. Broncheo- alveolar lavage fluid (BALF) and lung tissues were harvested at 12 and 24 weeks post irradiation for studying inflammatory and fibrotic markers. Lactate dehydrogenase (LDH) leakage, leukocyte count and protein content in BALF were used as parameters to evaluate lung vascular permeability. Inflammatory cell signaling (p38 phosphorylation) and anti-oxidant status (MnSOD and Catalase level) was assessed by Western blot, while X-ray CT scan, H & E staining and trichrome staining were done to study the lung architecture and collagen deposition. Irradiation of the lung increased the total protein content, LDH leakage and total leukocyte count in the BALF, reflecting endothelial barrier dysfunction. These disruptive effects were significantly abolished by DRDE-30, which appear to be linked to the DRDE-30 mediated abrogation of activation of the redox-sensitive pro- inflammatory signaling cascade, the MAPK pathway. Concurrent administration of DRDE-30 with radiation inhibited radiation-induced oxidative stress by strengthening the anti-oxidant defense system and abrogated p38 mitogen-activated protein kinase activation, which was associated with reduced vascular leak and macrophage recruitment to the lungs. Histopathological examination (by H & E staining) of the lung showed radiation-induced inflammation of the lungs, characterized by cellular infiltration, interstitial oedema, alveolar wall thickening, perivascular fibrosis and obstruction of alveolar spaces, which were all reduced by pre-administration of DRDE-30. Structural analysis with X-ray CT indicated lung architecture (linked to the degree of opacity) comparable to un-irradiated mice that correlated well with the lung morphology and reduced collagen deposition. Reduction in the radiation-induced inflammation and fibrosis brought about by DRDE-30 resulted in a profound increase in animal survival (72 % in the combination vs 24% with radiation) observed at the end of 24 weeks following irradiation. These findings establish the potential of the Amifostine analogue, DRDE-30, in reducing radiation induced pulmonary injury by attenuating the inflammatory and fibrotic responses.

Keywords: amifostine, fibrosis, inflammation, lung injury radiation

Procedia PDF Downloads 510

Authors: Shreya Saxena, Felix Miller-Molloy, Phillipa Bowen, Greg Fellows, Elizabeth Bowen

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Background: Complex fluid balance abnormalities are well-established post-neurosurgery and traumatic brain injury (TBI). The triple-phase response requires fluid management strategies reactive to urine output and sodium homeostasis as patients shift between Diabetes Insipidus (DI) and Syndrome of Inappropriate ADH (SIADH). It was observed, at a tertiary paediatric center, a relatively high prevalence of the above complications within a cohort of paediatric post-neurosurgical and TBI patients. An audit of the clinical practice against set institutional guidelines was undertaken and analyzed to understand why this was occurring. Based on those results, new guidelines were developed with structured educational packages for the specialist teams involved. This was then reaudited, and the findings were compared. Methods: Two independent audits were conducted across two time periods, pre and post guideline change. Primary data was collected retrospectively, including both qualitative and quantitative data sets from the CQUIN neurosurgical database and electronic medical records. All paediatric patients post posterior fossa (PFT) or supratentorial surgery or with a TBI were included. A literature review of evidence-based practice, initial audit data, and stakeholder feedback was used to develop new clinical guidelines and nursing standard operation procedures. Compliance against these newly developed guidelines was re-assessed and a thematic, trend-based analysis of the two sets of results was conducted. Results: Audit-1 January2017-June2018, n=80; Audit-2 January2020-June2021, n=30 (reduced operative capacity due to COVID-19 pandemic). Overall, improvements in the monitoring of both fluid balance and electrolyte trends were demonstrated; 51% vs. 77% and 78% vs. 94%, respectively. The number of clear fluid management plans documented postoperatively also increased (odds ratio of 4), leading to earlier recognition and management of evolving fluid-balance abnormalities. The local paediatric endocrine team was involved in the care of all complex cases and notified sooner for those considered to be developing DI or SIADH (14% to 35%). However, significant Na fluctuations (>12mmol in 24 hours) remained similar – 5 vs six patients – found to be due to complex pituitary hypothalamic pathology – and the recommended adaptive fluid management strategy was still not always used. Qualitative data regarding useability and understanding of fluid-balance abnormalities and the revised guidelines were obtained from health professionals via surveys and discussion in the specialist teams providing care. The feedback highlighted the new guidelines provided a more consistent approach to the post-operative care of these patients and was a better platform for communication amongst the different specialist teams involved. The potential limitation to our study would be the small sample size on which to conduct formal analyses; however, this reflects the population that we were investigating, which we cannot control. Conclusion: The revised clinical guidelines, based on audited data, evidence-based literature review and stakeholder consultations, have demonstrated an improvement in understanding of the neuro-endocrine complications that are possible, as well as increased compliance to post-operative monitoring of fluid balance and electrolytes in this cohort of patients. Emphasis has been placed on preventative rather than treatment of DI and SIADH. Consequently, this has positively impacted patient safety for the center and highlighted the importance of educational awareness and multi-disciplinary team working.

Keywords: post-operative, fluid-balance management, neuro-endocrine complications, paediatric

Procedia PDF Downloads 92

Authors: Hooshag Asadi Haroni, Maryam Veiskarami, Yongjun Lu

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The Dalli gold-rich porphyry deposit (17 Mt @ 0.5% Cu and 0.65 g/t Au) is located in the Urumieh-Dokhtar Magmatic Arc (UDMA), a small segment of the Tethyan metallogenic belt, hosting several porphyry Cu (Mo-Au) systems in Iran. This research characterizes the Dalli deposit to define exploration criteria in advanced exploration such as the drilling of possible blind porphyry centers. Geological map, trench/drill hole geochemical and ground magnetic data, and age dating and isotope trace element analyses, carried out at the John De Laeter Research Center of Curtin University, were used to characterize the Delli deposit. Mineralization at Dalli is hosted by NE-trending quartz-diorite porphyry stocks (~ 200m in diameter) intruded by a wall-rock andesite porphyry. Disseminated and stockwork Cu-Au mineralization is related to potassic alteration, comprising magnetite, late K-feldspar and biotite, and quartz-sericite-specularite overprint, surrounded by extensive barren argillic and propylitic alterations. In the peripheries of the porphyry centers, there are N-trending vuggy quartz veins, hosting epithermal Au-Ag-As-Sb mineralization. Geochemical analyses of drill core samples showed that the core of the porphyry stocks is low-grade, whereas the high-grade disseminated and stockwork mineralization (~ 1% Cu and ~ 1.2 g/t Au) occurred at the contact of the porphyry stocks and andesite porphyry. Geochemical studies of the drill hole and trench samples showed a strong correlation between Cu and Au and both show a second-order correlation with Fe and As. Magnetic survey revealed two significant magnetic anomalies, associated with intensive potassic alteration, in the reduced-to-the-pole magnetic map of the area. A relatively weaker magnetic anomaly, showing no surface porphyry expressions, is located on a lithocap, consisting of advanced argillic alteration, vuggy quartz veins, and surface expressions of epithermal geochemical signatures. The association of the lithocap and the weak magnetic anomaly could be indicative of a hidden mineralized porphyry center. Litho-geochemical analyses of the least altered Dalli intrusions and volcanic rocks indicated high Sr/Y (49-61) and Eu/Eu* (0.89-0.92), features typical of Cu porphyries. The U-Pb dating of zircons of the mineralized quartz diorite and andesite porphyry, carried out by laser ablation inductively coupled plasma mass spectrometry, yielded magmatic crystallization ages of 15.4-16.0 Ma (Middle Miocene). The zircon trace element concentrations of Dalli are characterized by high Eu/Eu* (0.3-0.8), (Ce/Nd)/Y (0.01-0.3), and 10000*(Eu/Eu*)/Y (2-15) ratios, similar to fertile porphyry suites such as the giant Sar-Cheshmeh and Qulong porphyry Cu deposits along the Tethyan belt. This suggests that the Middle Miocene Dalli intrusions are fertile and require extensive deep drillings to define their potential. Chondrite-normalized rare earth element (REE) patterns show no significant Eu anomalies, and are characterized by light-REE enrichments (La/Sm)n = 2.57–6.40). In normalized multi-element diagrams, analyzed rocks are characterized by enrichments in large ion lithophile elements (LILE) and depletions in high field strength elements (HFSE), and display typical features of subduction-related calc-alkaline magmas. The characteristics of the Dalli deposit provided several recognition criteria for detailed exploration of Cu-Au porphyry deposits and highlighted the importance of the UDMA as a potentially significant, economically important, but relatively underexplored porphyry province.

Keywords: porphyry, gold, geochronology, magnetic, exploration

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Authors: Gulce Kanturer Yasar, Hayriye Esbah Tuncay

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Cultivated food production systems have coexisted harmoniously with nature for thousands of years through ancient techniques. Based on this experience, experimentation, and discovery, these culturally embedded methods have evolved to sustain food production, restore ecosystems, and harmoniously adapt to nature. In this era, as we seek solutions to food security challenges, enhancing and repairing our food production systems is crucial, making them more resilient to future disasters without harming the ecosystem. Instead of unsustainable conventional systems with ongoing destructive effects, we must investigate innovative and restorative production systems that integrate ancient wisdom and technology. Whether we consider agricultural fields, pastures, forests, coastal wetland ecosystems, or lagoons, it is crucial to harness the potential of these natural resources in addressing future global challenges, fostering both socio-economic resilience and ecological sustainability through strategic organization for food production. When thoughtfully designed and managed, marine-based food production has the potential to function as a living infrastructure system that addresses social and environmental challenges despite its known adverse impacts on the environment and local economies. These areas are also stages of daily life, vibrant hubs where local culture is produced and shared, contributing to the distinctive rural character of coastal settlements and exhibiting numerous spatial expressions of public nature. When we consider the history of humanity, indigenous communities have engaged in these sustainable production practices that provide goods for food, trade, culture, and the environment for many ages. Ecosystem restoration and socio-economic resilience can be achieved by combining production techniques based on ecological knowledge developed by indigenous societies with modern technologies. Coastal lagoons are highly productive coastal features that provide various natural services and societal values. They are especially vulnerable to severe physical, ecological, and social impacts of changing, challenging global conditions because of their placement within the coastal landscape. Coastal lagoons are crucial in sustaining fisheries productivity, providing storm protection, supporting tourism, and offering other natural services that hold significant value for society. Although there is considerable literature on the physical and ecological dimensions of lagoons, much less literature focuses on their economic and social values. This study will discuss the possibilities of coastal lagoons to achieve both ecologically sustainable and socio-economically resilient while maintaining their productivity by combining local techniques and modern technologies. The case study will present Turkey’s traditional aquaculture method, "Dalyans," predominantly operated by small-scale farmers in coastal lagoons. Due to human, ecological, and economic factors, dalyans are losing their landscape characteristics and efficiency. These 1000-year-old ancient techniques, rooted in centuries of traditional and agroecological knowledge, are under threat of tourism, urbanization, and unsustainable agricultural practices. Thus, Dalyans have diminished from 29 to approximately 4-5 active Dalyans. To deal with the adverse socio-economic and ecological consequences on Turkey's coastal areas, conserving Dalyans by protecting their indigenous practices while incorporating contemporary methods is essential. This study seeks to generate scenarios that envision the potential ways protection and development can manifest within case study areas.

Keywords: coastal foodscape, lagoon aquaculture, regenerative food systems, watershed food networks

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Authors: Mehmet Salih Bayraktutan

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Geomechanical properties of Rock Salt Deposits in Tuzluca Salt Mine Area (Eastern Turkey) are studied for modeling the operation- excavation strategy. The purpose of this research focused on calculating the critical value of span height- which will meet the safety requirements. The Mine Site Tuzluca Hills consist of alternating parallel bedding of Salt ( NaCl ) and Gypsum ( CaS04 + 2 H20) rocks. Rock Salt beds are more resistant than narrow Gypsum interlayers. Rock Salt beds formed almost 97 percent of the total height of the Hill. Therefore, the geotechnical safety of Galleries depends on the mechanical criteria of Rock Salt Cores. General deposition of Tuzluca Basin was finally completed by Tuzluca Evaporites, as for the uppermost stratigraphic unit. They are currently running mining operations performed by classic mechanical excavation, room and pillar method. Rooms and Pillars are currently experiencing an initial stage of fracturing in places. Geotechnical safety of the whole mining area evaluated by Rock Mass Rating (RMR), Rock Quality Designation (RQD) spacing of joints, and the interaction of groundwater and fracture system. In general, bedded rock salt Show large lateral deformation capacity (while deformation modulus stays in relative small values, here E= 9.86 GPa). In such litho-stratigraphic environments, creep is a critical mechanism in failure. Rock Salt creep rate in steady-state is greater than interbedding layers. Under long-lasted compressive stresses, creep may cause shear displacements, partly using bedding planes. Eventually, steady-state creep in time returns to accelerated stages. Uniaxial compression creep tests on specimens were performed to have an idea of rock salt strength. To give an idea, on Rock Salt cores, average axial strength and strain are found as 18 - 24 MPa and 0.43-0.45 %, respectively. Uniaxial Compressive strength of 26- 32 MPa, from bedded rock salt cores. Elastic modulus is comparatively low, but lateral deformation of the rock salt is high under the uniaxial compression stress state. Poisson ratio = 0.44, break load = 156 kN, cohesion c= 12.8 kg/cm2, specific gravity SG=2.17 gr/cm3. Fracture System; spacing of fractures, joints, faults, offsets are evaluated under acting geodynamic mechanism. Two sand beds, each 4-6 m thick, exist near to upper level and at the top of the evaporating sequence. They act as aquifers and keep infiltrated water on top for a long duration, which may result in the failure of roofs or pillars. Two major active seismic ( N30W and N70E ) striking Fault Planes and parallel fracture strands have seismically triggered moderate risk of structural deformation of rock salt bedding sequence. Earthquakes and Floods are two prevailing sources of geohazards in this region—the seismotectonic activity of the Mine Site based on the crossing framework of Kagizman Faults and Igdir Faults. Dominant Hazard Risk sources include; a) Weak mechanical properties of rock salt, gypsum, anhydrite beds-creep. b) Physical discontinuities cutting across the thick parallel layers of Evaporite Mass, c) Intercalated beds of weak cemented or loose sand, clayey sandy sediments. On the other hand, absorbing the effects of salt-gyps parallel bedded deposits on seismic wave amplitudes has a reducing effect on the Rock Mass.

Keywords: bedded rock salt, creep, failure mechanism, geotechnical safety

Procedia PDF Downloads 190

Authors: Marcela Davalos Lopez

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The history of the circulation of hygienic knowledge and the consolidation of public health in Latin American cities towards the end of the 19th century is well known. Among them, Mexico City was inserted in international politics, strengthened institutions, medical knowledge, applied parameters of modernity and built sanitary engineering works. Despite the power that this hygienist system achieved, its scope was relative: it cannot be generalized to all cities. From a comparative and contextual analysis, it will be shown that conclusions derived from modern urban historiography present, from our contemporary observations, fractures. Between 1890 and 1930, the small cities and areas surrounding the Mexican capital adapted in their own way the international and federal public health regulations. This will be shown for neighborhoods located around Mexico City and in a medium city, close to the Mexican capital (about 80 km), called Cuernavaca. While the inhabitants of the neighborhoods kept awaiting the evolutionary process and the forms that public hygiene policies were taking (because they were witnesses and affected in their territories), in Cuernavaca, the dictates came as an echo. While the capital was drained, large roads were opened, roundabouts were erected, residents were expelled, and drains, sewers, drinking water pipes, etc., were built; Cuernavaca was sheltered in other times and practices. What was this due to? Undoubtedly, the time and energy that it took politicians and the group of "scientists" to carry out these enormous works in the Mexican capital took them away from addressing the issue in remote villages. It was not until the 20th century that the federal hygiene policy began to be strengthened. Despite this, there are other factors that emphasize the particularities of each site. I would like to draw attention here to the different receptions that each town prepared on public hygiene. We will see that Cuernavaca responded to its own semi-rural culture, history, orography and functions, prolonging for much longer, for example, the use of its deep ravines as sewers. For their part, the neighborhoods surrounding the capital, although affected and excluded from hygienist policies, chose to move away from them and solve the deficiencies with their own resources (they resorted to the waste that was left from the dried lake of Mexico to continue their lake practices). All of this points to a paradox that shapes our contemporary concerns: on the one hand, the benefits derived from medical knowledge and its technological applications (in this work referring particularly to the urban health system) and, on the other, the alteration it caused in environmental settings. Places like Cuernavaca (classified by the nineteenth-century and hygienists of the first decades of the twentieth century as backward), as well as landscapes such as neighborhoods, affected by advances in sanitary engineering, keep in their memory buried practices that we observe today as possible ways to reestablish environmental balances: alternative uses of water; recycling of organic materials; local uses of fauna; various systems for breaking down excreta, and so on. In sum, what the nineteenth and first half of the twentieth centuries graduated as levels of backwardness or progress, turn out to be key information to rethink the routes of environmental conservation. When we return to the observations of the scientists, politicians and lawyers of that period, we find historically rejected cultural alterity. Populations such as Cuernavaca that, due to their history, orography and/or insufficiency of federal policies, kept different relationships with the environment, today give us clues to reorient basic elements of cities: alternative uses of water, waste of raw materials, organic or consumption of local products, among others. It is, therefore, a matter of unearthing the rejected that cries out to emerge to the surface.

Keywords: sanitary hygiene, Mexico city, cultural alterity, environmental conservation, environmental history

Procedia PDF Downloads 164

Authors: Nino Kupatadze, Tamar Memanishvili, Natia Ochkhikidze, David Tugushi, Zaal Kokaia, Ramaz Katsarava

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Amino acid-based Biodegradable poly(ester-amide)s (PEAs) have gained considerable interest as a promising materials for numerous biomedical applications. These polymers reveal a high biocompatibility and easily form small particles suitable for delivery various biological, as well as elastic bio-erodible films serving as matrices for constructing antibacterial coatings. In the present work we have demonstrated a potential of the PEAs for two applications: 1. cell therapy for stroke as vehicles for delivery and sustained release of growth factors, 2. bactericidal coating as prevention biofilm and applicable in infected wound management. Stroke remains the main cause of adult disability with limited treatment options. Although stem cell therapy is a promising strategy, it still requires improvement of cell survival, differentiation and tissue modulation. .Recently, microspheres (MPs) made of biodegradable polymers have gained significant attention for providing necessary support of transplanted cells. To investigate this strategy in the cell therapy of stroke, MPs loaded with transcription factors Wnt3A/BMP4 were prepared. These proteins have been shown to mediate the maturation of the cortical neurons. We have suggested that implantation of these materials could create a suitable microenvironment for implanted cells. Particles with spherical shape, porous surface, and 5-40 m in size (monitored by scanning electron microscopy) were made on the basis of the original PEA composed of adipic acid, L-phenylalanine and 1,4-butanediol. After 4 months transplantation of MPs in rodent brain, no inflammation was observed. Additionally, factors were successfully released from MPs and affected neuronal cell differentiation in in vitro. The in vivo study using loaded MPs is in progress. Another severe problem in biomedicine is prevention of surgical devices from biofilm formation. Antimicrobial polymeric coatings are most effective “shields” to protect surfaces/devices from biofilm formation. Among matrices for constructing the coatings preference should be given to bio-erodible polymers. Such types of coatings will play a role of “unstable seating” that will not allow bacteria to occupy the surface. In other words, bio-erodible coatings would be discomfort shelter for bacteria that along with releasing “killers of bacteria” should prevent the formation of biofilm. For this purpose, we selected an original biodegradable PEA composed of L-leucine, 1,6-hexanediol and sebacic acid as a bio-erodible matrix, and nanosilver (AgNPs) as a bactericidal agent (“killer of bacteria”). Such nanocomposite material is also promising in treatment of superficial wound and ulcer. The solubility of the PEA in ethanol allows to reduce AgNO3 to NPs directly in the solution, where the solvent served as a reductive agent, and the PEA served as NPs stabilizer. The photochemical reduction was selected as a basic method to form NPs. The obtained AgNPs were characterized by UV-spectroscopy, transmission electron microscope (TEM), and dynamic light scattering (DLS). According to the UV-data and TEM data the photochemical reduction resulted in spherical AgNPs with wide particle size distribution with a high contribution of the particles below 10 nm that are known as responsible for bactericidal activity of AgNPs. DLS study showed that average size of nanoparticles formed after photo-reduction in ethanol solution ranged within ca. 50 nm.

Keywords: biodegradable polymers, microparticles, nanocomposites, stem cell therapy, stroke

Procedia PDF Downloads 395

Authors: A. Aceranti, L. Moretti, S. Vernocchi, M. Colorato, P. Caristia

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Irritable bowel syndrome (IBS) is the association between abdominal pain, abdominal distension and intestinal dysfunction for recurring periods. About 10% of the world's population has IBS at any given time in their life, and about 200 people per 100,000 receive an initial diagnosis of IBS each year. Persistent pain is recognized as one of the most pervasive and challenging problems facing the medical community today. Persistent pain is considered more as a complex pathophysiological, diagnostic and therapeutic situation rather than as a persistent symptom. The low efficiency of conventional drug treatments has led many doctors to become interested in the non-drug alternative treatment of IBS, especially for more severe cases. Patients and providers are often dissatisfied with the available drug remedies and often seek complementary and alternative medicine (CAM), a unique and holistic approach to treatment that is not a typical component of conventional medicine. Osteopathic treatment may be of specific interest in patients with IBS. Osteopathy is a complementary health approach that emphasizes the role of the musculoskeletal system in health and promotes optimal function of the body's tissues using a variety of manual techniques to improve body function. Osteopathy has been defined as a patient-centered health discipline based on the principles of interrelation between body structure and function, the body's innate capacity for self-healing and the adoption of a whole person health approach. mainly by practicing manual processing. Studies reported that osteopathic manual treatment (OMT) reduced IBS symptoms, such as abdominal pain, constipation, diarrhea, and improved general well-being. The focus in the treatment of IBS with osteopathy has gone beyond simple spinal alignment, to directly address the abnormal physiology of the body using a series of direct and indirect techniques. The topic of this study was chosen for different reasons: due to the large number of people involved who suffer from this disorder and for the dysfunction itself, since nowadays there is still little clarity about the best type of treatment and, above all, to its origin. The visceral component in the osteopathic field is still a world to be discovered, although it is related to a large part of patient series, it has contents that affect numerous disciplines and this makes it an enigma yet to be solved. The study originated in the didactic practice where the curiosity of a topic is marked that, even today, no one is able to explain and, above all, cure definitively. The main purpose of this study is to try to create a good basis on the osteopathic discipline for subsequent studies that can be exhaustive in the best possible way, resolving some doubts about which treatment modality can be used with more relevance. The path was decided to structure it in such a way that 3 types of osteopathic treatment are used on 3 groups of people who will be selected after completing a questionnaire, which will deem them suitable for the study. They will, in fact, be divided into three groups where: - the first group was given a visceral osteopathic treatment. - The second group was given a manual osteopathic treatment of neurological stimulation. - The third group received a placebo treatment. At the end of the treatment, questionnaires will be re-proposed respectively one week after the session and one month after the treatment from which any data will be collected that will demonstrate the effectiveness or otherwise of the treatment received. The sample of 50 patients examined underwent an oral interview to evaluate the inclusion and exclusion criteria to participate in the study. Of the 50 patients questioned, 17 people who underwent different osteopathic techniques were eligible for the study. Comparing the data related to the first assessment of tenderness and frequency of symptoms with the data related to the first follow-up shows a significant improvement in the score assigned to the different questions, especially in the neurogenic and visceral groups. We are aware of the fact that it is a study performed on a small sample of patients, and this is a penalizing factor. We remain, however, convinced that having obtained good results in terms of subjective improvement in the quality of life of the subjects, it would be very interesting to re-propose the study on a larger sample and fill the gaps.

Keywords: IBS, osteopathy, colon, intestinal inflammation

Procedia PDF Downloads 101

Authors: P. J. Sweeney, T. Ahtoniemi, J. Puoliväli, T. Laitinen, K.Lehtimäki, A. Nurmi, D. Wells

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Duchenne muscular dystrophy (DMD) is an X-linked, lethal muscle wasting disease for which there are currently no treatment that effectively prevents the muscle necrosis and progressive muscle loss. DMD is among the most common of inherited diseases affecting around 1/3500 live male births. MDX (X-linked muscular dystrophy) mice only partially encapsulate the disease in humans and display weakness in muscles, muscle damage and edema during a period deemed the “critical period” when these mice go through cycles of muscular degeneration and regeneration. Although the MDX mutant mouse model has been extensively studied as a model for DMD, to-date an extensive temporal, non-invasive imaging profile that utilizes magnetic resonance imaging (MRI) and 1H-magnetic resonance spectroscopy (1H-MRS) has not been performed.. In addition, longitudinal imaging characterization has not coincided with attempts to exacerbate the progressive muscle damage by exercise. In this study we employed an 11.7 T small animal MRI in order to characterize the MRI and MRS profile of MDX mice longitudinally during a 12 month period during which MDX mice were subjected to exercise. Male mutant MDX mice (n=15) and male wild-type mice (n=15) were subjected to a chronic exercise regime of treadmill walking (30 min/ session) bi-weekly over the whole 12 month follow-up period. Mouse gastrocnemius and tibialis anterior muscles were profiled with baseline T2-MRI and 1H-MRS at 6 weeks of age. Imaging and spectroscopy was repeated again at 3 months, 6 months, 9 months and 12 months of age. Plasma creatine kinase (CK) level measurements were coincided with time-points for T2-MRI and 1H-MRS, but also after the “critical period” at 10 weeks of age. The results obtained from this study indicate that chronic exercise extends dystrophic phenotype of MDX mice as evidenced by T2-MRI and1H-MRS. T2-MRI revealed extent and location of the muscle damage in gastrocnemius and tibialis anterior muscles as hyperintensities (lesions and edema) in exercised MDX mice over follow-up period.. The magnitude of the muscle damage remained stable over time in exercised mice. No evident fat infiltration or cumulation to the muscle tissues was seen at any time-point in exercised MDX mice. Creatine, choline and taurine levels evaluated by 1H-MRS from the same muscles were found significantly decreased in each time-point, Extramyocellular (EMCL) and intramyocellular lipids (IMCL) did not change in exercised mice supporting the findings from anatomical T2-MRI scans for fat content. Creatine kinase levels were found to be significantly higher in exercised MDX mice during the follow-up period and importantly CK levels remained stable over the whole follow-up period. Taken together, we have described here longitudinal prophile for muscle damage and muscle metabolic changes in MDX mice subjected to chronic exercised. The extent of the muscle damage by T2-MRI was found to be stable through the follow-up period in muscles examined. In addition, metabolic profile, especially creatine, choline and taurine levels in muscles, was found to be sustained between time-points. The anatomical muscle damage evaluated by T2-MRI was supported by plasma CK levels which remained stable over the follow-up period. These findings show that non-invasive imaging and spectroscopy can be used effectively to evaluate chronic muscle pathology. These techniques can be also used to evaluate the effect of various manipulations, like here exercise, on the phenotype of the mice. Many of the findings we present here are translatable to clinical disease, such as decreased creatine, choline and taurine levels in muscles. Imaging by T2-MRI and 1H-MRS also revealed that fat content or extramyocellar and intramyocellular lipids, respectively, are not changed in MDX mice, which is in contrast to clinical manifestation of the Duchenne’s muscle dystrophy. Findings show that non-invasive imaging can be used to characterize the phenotype of a MDX model and its translatability to clinical disease, and to study events that have traditionally been not examined, like here rigorous exercise related sustained muscle damage after the “critical period”. The ability for this model to display sustained damage beyond the spontaneous “critical period“ and in turn to study drug effects on this extended phenotype will increase the value of the MDX mouse model as a tool to study therapies and treatments aimed at DMD and associated diseases.

Keywords: 1H-MRS, MRI, muscular dystrophy, mouse model

Procedia PDF Downloads 357

Authors: Leila Safazadeh, Brad Berron

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Self-assembled monolayers have tremendous impact in interfacial science, due to the unique opportunity they offer to tailor surface properties. Low-density self-assembled monolayers are an emerging class of monolayers where the environment-interfacing portion of the adsorbate has a greater level of conformational freedom when compared to traditional monolayer chemistries. This greater range of motion and increased spacing between surface-bound molecules offers new opportunities in tailoring adsorption phenomena in sensing systems. In particular, we expect low-density surfaces to offer a unique opportunity to intercalate surface bound ligands into the secondary structure of protiens and other macromolecules. Additionally, as many conventional sensing surfaces are built upon gold surfaces (SPR or QCM), these surfaces must be compatible with gold substrates. Here, we present the first stable method of generating low-density self assembled monolayer surfaces on gold for the analysis of their interactions with protein targets. Our approach is based on the 2:1 addition of thiol-yne chemistry to develop new classes of y-shaped adsorbates on gold, where the environment-interfacing group is spaced laterally from neighboring chemical groups. This technique involves an initial deposition of a crystalline monolayer of 1,10 decanedithiol on the gold substrate, followed by grafting of a low-packed monolayer on through a photoinitiated thiol-yne reaction in presence of light. Orthogonality of the thiol-yne chemistry (commonly referred to as a click chemistry) allows for preparation of low-density monolayers with variety of functional groups. To date, carboxyl, amine, alcohol, and alkyl terminated monolayers have been prepared using this core technology. Results from surface characterization techniques such as FTIR, contact angle goniometry and electrochemical impedance spectroscopy confirm the proposed low chain-chain interactions of the environment interfacing groups. Reductive desorption measurements suggest a higher stability for the click-LDMs compared to traditional SAMs, along with the equivalent packing density at the substrate interface, which confirms the proposed stability of the monolayer-gold interface. In addition, contact angle measurements change in the presence of an applied potential, supporting our description of a surface structure which allows the alkyl chains to freely orient themselves in response to different environments. We are studying the differences in protein adsorption phenomena between well packed and our loosely packed surfaces, and we expect this data will be ready to present at the GRC meeting. This work aims to contribute biotechnology science in the following manner: Molecularly imprinted polymers are a promising recognition mode with several advantages over natural antibodies in the recognition of small molecules. However, because of their bulk polymer structure, they are poorly suited for the rapid diffusion desired for recognition of proteins and other macromolecules. Molecularly imprinted monolayers are an emerging class of materials where the surface is imprinted, and there is not a bulk material to impede mass transfer. Further, the short distance between the binding site and the signal transduction material improves many modes of detection. My dissertation project is to develop a new chemistry for protein-imprinted self-assembled monolayers on gold, for incorporation into SPR sensors. Our unique contribution is the spatial imprinting of not only physical cues (seen in current imprinted monolayer techniques), but to also incorporate complementary chemical cues. This is accomplished through a photo-click grafting of preassembled ligands around a protein template. This conference is important for my development as a graduate student to broaden my appreciation of the sensor development beyond surface chemistry.

Keywords: low-density self-assembled monolayers, thiol-yne click reaction, molecular imprinting

Procedia PDF Downloads 226

Authors: Z. S. Haidar

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Millions of teeth are removed annually, and dental extraction is one of the most commonly performed surgical procedures globally. Whether due to caries, periodontal disease, or trauma, exodontia and the ensuing wound healing and bone remodeling processes of the resultant socket (hole in the jaw bone) usually result in serious deformities of the residual alveolar osseous ridge and surrounding soft tissues (reduced height/width). Such voluminous changes render the placement of a proper conventional bridge, denture, or even an implant-supported prosthesis extremely challenging. Further, most extractions continue to be performed with no regard for preventing the onset of alveolar osteitis (also known as dry socket, a painful and difficult-to-treat/-manage condition post-exodontia). Hence, such serious resorptive morphological changes often result in significant facial deformities and a negative impact on the overall Quality of Life (QoL) of patients (and oral health-related QoL); alarming, particularly for the geriatric with compromised healing and in light of the thriving longevity statistics. Despite advances in tissue/wound grafting, serious limitations continue to exist, including efficacy and clinical outcome predictability, cost, treatment time, expertise, and risk of immune reactions. For cases of dry socket, specifically, the commercially available and often-prescribed home remedies are highly-lacking. Indeed, most are not recommended for use anymore. Alveogyl is a fine example. Hence, there is a great market demand and need for alternative solutions. Herein, SockGEL/PLUG (patent pending), an innovative, all-natural, drug-free, and injectable thermo-responsive hydrogel, was designed, formulated, characterized, and evaluated as an osteogenic, angiogenic, anti-microbial, and pain-soothing suture-free intra-alveolar dressing, safe and efficacious for use in fresh extraction sockets, immediately post-exodontia. It is composed of FDA-approved, biocompatible and biodegradable polymers, self-assembled electro-statically to formulate a scaffolding matrix to (1) prevent the on-set of alveolar osteitis via securing the fibrin-clot in situ and protecting/sealing the socket from contamination/infection; and (2) endogenously promote/accelerate wound healing and bone remodeling to preserve the volume of the alveolus. The intrinsic properties of the SockGEL/PLUG hydrogel were evaluated physical-chemical-mechanically for safety (cell viability), viscosity, rheology, bio-distribution, and essentially, capacity to induce wound healing and osteogenesis (small defect, in vivo) without any signaling cues from exogenous cells, growth factors or drugs. The proposed animal model of cranial critical-sized and non-vascularized bone defects shall provide new and critical insights into the role and mechanism of the employed natural bio-polymer blend and gel product in endogenous reparative regeneration of soft tissues and bone morphogenesis. Alongside, the fine-tuning of our modified formulation method will further tackle appropriateness, reproducibility, scalability, ease, and speed in producing stable, biodegradable, and sterilizable thermo-sensitive matrices (3-dimensional interpenetrating yet porous polymeric network) suitable for the intra-socket application. Findings are anticipated to provide sufficient evidence to translate into pilot clinical trials and validate the innovation before engaging the market for feasibility, acceptance, and cost-effectiveness studies.

Keywords: hydrogel, nanotechnology, bioengineering, bone regeneration, nanogel, drug delivery

Procedia PDF Downloads 112

Authors: Erika T. Fajardo-Ariza, Luis A. Castillo-Sanabria, Andrea Nieto-Veloza, Carlos M. Zuluaga-Domínguez

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The growing emphasis on sustainable food production and preservation has driven the development of innovative solutions to minimize postharvest losses and improve market access for small-scale farmers. This project focuses on designing, constructing, and selecting materials for solar dryers in certain regions of Colombia where inadequate infrastructure limits access to major commercial hubs. Postharvest losses pose a significant challenge, impacting food security and farmer income. Addressing these losses is crucial for enhancing the value of agricultural products and supporting local economies. A comprehensive survey of local farmers revealed substantial challenges, including limited market access, inefficient transportation, and significant postharvest losses. For crops such as coffee, bananas, and citrus fruits, losses range from 0% to 50%, driven by factors like labor shortages, adverse climatic conditions, and transportation difficulties. To address these issues, the project prioritized selecting effective materials for the solar dryer. Various materials, recovered acrylic, original acrylic, glass, and polystyrene, were tested for their performance. The tests showed that recovered acrylic and glass were most effective in increasing the temperature difference between the interior and the external environment. The solar dryer was designed using Fusion 360® software (Autodesk, USA) and adhered to architectural guidelines from Architectural Graphic Standards. It features up to sixteen aluminum trays, each with a maximum load capacity of 3.5 kg, arranged in two levels to optimize drying efficiency. The constructed dryer was then tested with two locally available plant materials: green plantains (Musa paradisiaca L.) and snack bananas (Musa AA Simonds). To monitor performance, Thermo hygrometers and an Arduino system recorded internal and external temperature and humidity at one-minute intervals. Despite challenges such as adverse weather conditions and delays in local government funding, the active involvement of local producers was a significant advantage, fostering ownership and understanding of the project. The solar dryer operated under conditions of 31°C dry bulb temperature (Tbs), 55% relative humidity, and 21°C wet bulb temperature (Tbh). The drying curves showed a consistent drying period with critical moisture content observed between 200 and 300 minutes, followed by a sharp decrease in moisture loss, reaching an equilibrium point after 3,400 minutes. Although the solar dryer requires more time and is highly dependent on atmospheric conditions, it can approach the efficiency of an electric dryer when properly optimized. The successful design and construction of solar dryer systems in difficult-to-access areas represent a significant advancement in agricultural sustainability and postharvest loss reduction. By choosing effective materials such as recovered acrylic and implementing a carefully planned design, the project provides a valuable tool for local farmers. The initiative not only improves the quality and marketability of agricultural products but also offers broader environmental benefits, such as reduced reliance on fossil fuels and decreased waste. Additionally, it supports economic growth by enhancing the value of crops and potentially increasing farmer income. The successful implementation and testing of the dryer, combined with the engagement of local stakeholders, highlight its potential for replication and positive impact in similar contexts.

Keywords: drying technology, postharvest loss reduction, solar dryers, sustainable agriculture

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Authors: Katerina Zaharieva, Katya Milenova, Zara Cherkezova-Zheleva, Alexander Eliyas, Boris Kunev, Ivan Mitov

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The synthesized nanosized manganese ferrite-type of samples have been tested as photocatalysts in the reaction of oxidative degradation of model contaminant Reactive Black 5 (RB5) dye in aqueous solutions under UV irradiation. As it is known this azo dye is applied in the textile-coloring industry and it is discharged into the waterways causing pollution. The co-precipitation procedure has been used for the synthesis of manganese ferrite-type of materials: Sample 1 - Mn0.25Fe2.75O4, Sample 2 - Mn0.5Fe2.5O4 and Sample 3 - MnFe2O4 from 0.03M aqueous solutions of MnCl2•4H2O, FeCl2•4H2O and/or FeCl3•6H2O and 0.3M NaOH in appropriate amounts. The mechanochemical activation of co-precipitated ferrite-type of samples has been performed in argon (Samples 1 and 2) or in air atmosphere (Sample 3) for 2 hours at a milling speed of 500 rpm. The mechano-chemical treatment has been carried out in a high energy planetary ball mill type PM 100, Retsch, Germany. The mass ratio between balls and powder was 30:1. As a result mechanochemically activated Sample 4 - Mn0.25Fe2.75O4, Sample 5 - Mn0.5Fe2.5O4 and Sample 6 - MnFe2O4 have been obtained. The synthesized manganese ferrite-type photocatalysts have been characterized by X-ray diffraction method and Moessbauer spectroscopy. The registered X-ray diffraction patterns and Moessbauer spectra of co-precipitated ferrite-type of materials show the presence of manganese ferrite and additional akaganeite phase. The presence of manganese ferrite and small amounts of iron phases is established in the mechanochemically treated samples. The calculated average crystallite size of manganese ferrites varies within the range 7 – 13 nm. This result is confirmed by Moessbauer study. The registered spectra show superparamagnetic behavior of the prepared materials at room temperature. The photocatalytic investigations have been made using polychromatic UV-A light lamp (Sylvania BLB, 18 W) illumination with wavelength maximum at 365 nm. The intensity of light irradiation upon the manganese ferrite-type photocatalysts was 0.66 mW.cm-2. The photocatalytic reaction of oxidative degradation of RB5 dye was carried out in a semi-batch slurry photocatalytic reactor with 0.15 g of ferrite-type powder, 150 ml of 20 ppm dye aqueous solution under magnetic stirring at rate 400 rpm and continuously feeding air flow. The samples achieved adsorption-desorption equilibrium in the dark period for 30 min and then the UV-light was turned on. After regular time intervals aliquot parts from the suspension were taken out and centrifuged to separate the powder from solution. The residual concentrations of dye were established by a UV-Vis absorbance single beam spectrophotometer CamSpec M501 (UK) measuring in the wavelength region from 190 to 800 nm. The photocatalytic measurements determined that the apparent pseudo-first-order rate constants calculated by linear slopes approximating to first order kinetic equation, increase in following order: Sample 3 (1.1х10-3 min-1) < Sample 1 (2.2х10-3 min-1) < Sample 2 (3.3 х10-3 min-1) < Sample 4 (3.8х10-3 min-1) < Sample 6 (11х10-3 min-1) < Sample 5 (15.2х10-3 min-1). The mechanochemically activated manganese ferrite-type of photocatalyst samples show significantly higher degree of oxidative degradation of RB5 dye after 120 minutes of UV light illumination in comparison with co-precipitated ferrite-type samples: Sample 5 (92%) > Sample 6 (91%) > Sample 4 (63%) > Sample 2 (53%) > Sample 1 (42%) > Sample 3 (15%). Summarizing the obtained results we conclude that the mechanochemical activation leads to a significant enhancement of the degree of oxidative degradation of the RB5 dye and photocatalytic activity of tested manganese ferrite-type of catalyst samples under our experimental conditions. The mechanochemically activated Mn0.5Fe2.5O4 ferrite-type of material displays the highest photocatalytic activity (15.2х10-3 min-1) and degree of oxidative degradation of the RB5 dye (92%) compared to the other synthesized samples. Especially a significant improvement in the degree of oxidative degradation of RB5 dye (91%) has been determined for mechanochemically treated MnFe2O4 ferrite-type of sample with the highest extent of substitution of iron ions by manganese ions than in the case of the co-precipitated MnFe2O4 sample (15%). The mechanochemically activated manganese ferrite-type of samples show good photocatalytic properties in the reaction of oxidative degradation of RB5 azo dye in aqueous solutions and it could find potential application for dye removal from wastewaters originating from textile industry.

Keywords: nanostructured manganese ferrite-type materials, photocatalytic activity, Reactive Black 5, water treatment

Procedia PDF Downloads 347

Authors: Claire Harrison, Raajit K. Rampal, Vikas Gupta, Srdan Verstovsek, Moshe Talpaz, Jean-Jacques Kiladjian, Ruben Mesa, Andrew Kuykendall, Alessandro Vannucchi, Francesca Palandri, Sebastian Grosicki, Timothy Devos, Eric Jourdan, Marielle J. Wondergem, Haifa Kathrin Al-Ali, Veronika Buxhofer-Ausch, Alberto Alvarez-Larrán, Sanjay Akhani, Rafael Muñoz-Carerras, Yury Sheykin, Gozde Colak, Morgan Harris, John Mascarenhas

Abstract:

Myelofibrosis (MF) is characterized by bone marrow fibrosis, anemia, splenomegaly and constitutional symptoms. Progressive bone marrow fibrosis results from aberrant megakaryopoeisis and expression of proinflammatory cytokines, both of which are heavily influenced by bromodomain and extraterminal domain (BET)-mediated gene regulation and lead to myeloproliferation and cytopenias. Pelabresib (CPI-0610) is an oral small-molecule investigational inhibitor of BET protein bromodomains currently being developed for the treatment of patients with MF. It is designed to downregulate BET target genes and modify nuclear factor kappa B (NF-κB) signaling. MANIFEST-2 was initiated based on data from Arm 3 of the ongoing Phase 2 MANIFEST study (NCT02158858), which is evaluating the combination of pelabresib and ruxolitinib in Janus kinase inhibitor (JAKi) treatment-naïve patients with MF. Primary endpoint analyses showed splenic and symptom responses in 68% and 56% of 84 enrolled patients, respectively. MANIFEST-2 (NCT04603495) is a global, Phase 3, randomized, double-blind, active-control study of pelabresib and ruxolitinib versus placebo and ruxolitinib in JAKi treatment-naïve patients with primary MF, post-polycythemia vera MF or post-essential thrombocythemia MF. The aim of this study is to evaluate the efficacy and safety of pelabresib in combination with ruxolitinib. Here we report updates from a recent protocol amendment. The MANIFEST-2 study schema is shown in Figure 1. Key eligibility criteria include a Dynamic International Prognostic Scoring System (DIPSS) score of Intermediate-1 or higher, platelet count ≥100 × 10^9/L, spleen volume ≥450 cc by computerized tomography or magnetic resonance imaging, ≥2 symptoms with an average score ≥3 or a Total Symptom Score (TSS) of ≥10 using the Myelofibrosis Symptom Assessment Form v4.0, peripheral blast count <5% and Eastern Cooperative Oncology Group performance status ≤2. Patient randomization will be stratified by DIPSS risk category (Intermediate-1 vs Intermediate-2 vs High), platelet count (>200 × 10^9/L vs 100–200 × 10^9/L) and spleen volume (≥1800 cm^3 vs <1800 cm^3). Double-blind treatment (pelabresib or matching placebo) will be administered once daily for 14 consecutive days, followed by a 7 day break, which is considered one cycle of treatment. Ruxolitinib will be administered twice daily for all 21 days of the cycle. The primary endpoint is SVR35 response (≥35% reduction in spleen volume from baseline) at Week 24, and the key secondary endpoint is TSS50 response (≥50% reduction in TSS from baseline) at Week 24. Other secondary endpoints include safety, pharmacokinetics, changes in bone marrow fibrosis, duration of SVR35 response, duration of TSS50 response, progression-free survival, overall survival, conversion from transfusion dependence to independence and rate of red blood cell transfusion for the first 24 weeks. Study recruitment is ongoing; 400 patients (200 per arm) from North America, Europe, Asia and Australia will be enrolled. The study opened for enrollment in November 2020. MANIFEST-2 was initiated based on data from the ongoing Phase 2 MANIFEST study with the aim of assessing the efficacy and safety of pelabresib and ruxolitinib in JAKi treatment-naïve patients with MF. MANIFEST-2 is currently open for enrollment.

Keywords: CPI-0610, JAKi treatment-naïve, MANIFEST-2, myelofibrosis, pelabresib

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