Search results for: Sustained Attention to Response Task (SART)

Authors: Pedro J. Rolim-Neto, Leslie R. M. Ferraz, Fabiana L. A. Santos, Pablo A. Ferreira, Ricardo T. L. Maia-Jr., Magaly A. M. Lyra, Danilo A F. Fonte, Salvana P. M. Costa, Amanda C. Q. M. Vieira, Larissa A. Rolim

Abstract:

Initially developed as an antimalarial agent, hydroxychloroquine (HCQ) sulfate is often used as a slow-acting antirheumatic drug in the treatment of disorders of connective tissue. The United States Pharmacopeia (USP) 37 provides a reversed-phase HPLC method for quantification of HCQ. However, this method was not reproducible, producing asymmetric peaks in a long analysis time. The asymmetry of the peak may cause an incorrect calculation of the concentration of the sample. Furthermore, the analysis time is unacceptable, especially regarding the routine of a pharmaceutical industry. The aiming of this study was to develop a fast, easy and efficient method for quantification of HCQ sulfate by High Performance Liquid Chromatography (HPLC) based on the Quality by Design (QbD) methodology. This method was optimized in terms of peak symmetry using the surface area graphic as the Design of Experiments (DoE) and the tailing factor (TF) as an indicator to the Design Space (DS). The reference method used was that described at USP 37 to the quantification of the drug. For the optimized method, was proposed a 33 factorial design, based on the QbD concepts. The DS was created with the TF (in a range between 0.98 and 1.2) in order to demonstrate the ideal analytical conditions. Changes were made in the composition of the USP mobile-phase (USP-MP): USP-MP: Methanol (90:10 v/v, 80:20 v/v and 70:30 v/v), in the flow (0.8, 1.0 and 1.2 mL) and in the oven temperature (30, 35, and 40ºC). The USP method allowed the quantification of drug in a long time (40-50 minutes). In addition, the method uses a high flow rate (1,5 mL.min-1) which increases the consumption of expensive solvents HPLC grade. The main problem observed was the TF value (1,8) that would be accepted if the drug was not a racemic mixture, since the co-elution of the isomers can become an unreliable peak integration. Therefore, the optimization was suggested in order to reduce the analysis time, aiming a better peak resolution and TF. For the optimization method, by the analysis of the surface-response plot it was possible to confirm the ideal setting analytical condition: 45 °C, 0,8 mL.min-1 and 80:20 USP-MP: Methanol. The optimized HPLC method enabled the quantification of HCQ sulfate, with a peak of high resolution, showing a TF value of 1,17. This promotes good co-elution of isomers of the HCQ, ensuring an accurate quantification of the raw material as racemic mixture. This method also proved to be 18 times faster, approximately, compared to the reference method, using a lower flow rate, reducing even more the consumption of the solvents and, consequently, the analysis cost. Thus, an analytical method for the quantification of HCQ sulfate was optimized using QbD methodology. This method proved to be faster and more efficient than the USP method, regarding the retention time and, especially, the peak resolution. The higher resolution in the chromatogram peaks supports the implementation of the method for quantification of the drug as racemic mixture, not requiring the separation of isomers.

Keywords: analytical method, hydroxychloroquine sulfate, quality by design, surface area graphic

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Authors: Yang Yang, Luciana Magalhães Rebelo Alencar, Martha Sahylí Ortega Pijeira, Beatriz da Silva Batista, Alefe Roger Silva França, Erick Rafael Dias Rates, Ruana Cardoso Lima, Sara Gemini-Piperni, Ralph Santos-Oliveira

Abstract:

Radium-²²³ dichloride ([²²³Rₐ]RₐCl₂) is an alpha particle-emitting radiopharmaceutical currently approved for the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases, and no known visceral metastatic disease. [²²³Rₐ]RₐCl₂ is bone-seeking calcium mimetic that bonds into the newly formed bone stroma, especially osteoblastic or sclerotic metastases, killing the tumor cells by inducing DNA breaks in a potent and localized manner. Nonetheless, the successful therapy of osteosarcoma as primary bone tumors is still a challenge. Nanomicelles are colloidal nanosystems widely used in drug development to improve blood circulation time, bioavailability, and specificity of therapeutic agents, among other applications. In addition, the enhanced permeability and retention effect of the nanosystems, and the renal excretion of the nanomicelles reported in most cases so far, are very attractive to achieve selective and increased accumulation in tumor site as well as to increase the safety of [²²³Rₐ]RₐCl₂ in the clinical routine. In the present work, [²²³Rₐ]RₐCl₂ nanomicelles were produced, characterized, in vitro evaluated, and compared with pure [²²³Rₐ]RₐCl2 solution using SAOS2 osteosarcoma cells. The [²²³Rₐ]RₐCl₂ nanomicelles were prepared using the amphiphilic copolymer Pluronic F127. The dynamic light scattering analysis of freshly produced [²²³Rₐ]RₐCl₂ nanomicelles demonstrated a mean size of 129.4 nm with a polydispersity index (PDI) of 0.303. After one week stored in the refrigerator, the mean size of the [²²³Rₐ]RₐCl₂ nanomicelles increased to 169.4 with a PDI of 0.381. Atomic force microscopy analysis of [223Rₐ]RₐCl₂ nanomicelles exhibited spherical structures whose heights reach 1 µm, suggesting the filling of 127-Pluronic nanomicelles with [²²³Rₐ]RₐCl₂. The viability assay with [²²³Rₐ]RₐCl₂ nanomicelles displayed a dose-dependent response as it was observed using pure [²²³Rₐ]RₐCl2. However, at the same dose, [²²³Rₐ]RₐCl₂ nanomicelles were 20% higher efficient in killing SAOS2 cells when compared with pure [²²³Rₐ]RₐCl₂. These findings demonstrated the effectiveness of the nanosystem validating the application of nanotechnology in targeted alpha therapy with [²²³Ra]RₐCl₂. In addition, the [²²³Rₐ]RaCl₂nanomicelles may be decorated and incorporated with a great variety of agents and compounds (e.g., monoclonal antibodies, aptamers, peptides) to overcome the limited use of [²²³Ra]RₐCl₂.

Keywords: nanomicelles, osteosarcoma, radium dichloride, targeted alpha therapy

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Authors: Shawn P. Daly

Abstract:

Communities heavily engaged in the tourism industry discover their values intersect, meld, and conflict with those of visitors. Maintaining cultural integrity in the face of powerful external pressures causes stress among society members. This effect represents a less studied aspect of sustainable tourism. The present paper brings a perspective unique to the tourism literature: biculturalism. The grounded theories, coherent hypotheses, and validated constructs and indicators of biculturalism represent a sound base from which to consider sociocultural issues in sustainable tourism. Five models describe the psychological state of individuals operating at cultural crossroads: assimilation (joining the new culture), acculturation (grasping the new culture but remaining of the original culture), alternation (varying behavior to cultural context), multicultural (maintaining distinct cultures), and fusion (blending cultures). These five processes divide into two units of analysis (individual and society), permitting research questions at levels important for considering sociocultural sustainability. Acculturation modelling has morphed into dual processes of acculturation (new culture adaptation) and enculturation (original culture adaptation). This dichotomy divides sustainability research questions into human impacts from assimilation (acquiring new culture, throwing away original), separation (rejecting new culture, keeping original), integration (acquiring new culture, keeping original), and marginalization (rejecting new culture, throwing away original). Biculturalism is often cast in terms of its emotional, behavioral, and cognitive dimensions. Required cultural adjustments and varying levels of cultural competence lead to physical, psychological, and emotional outcomes, including depression, lowered life satisfaction and self-esteem, headaches, and back pain—or enhanced career success, social skills, and life styles. Numerous studies provide empirical scales and research hypotheses for sustainability research into tourism’s causality and effect on local well-being. One key issue in applying biculturalism to sustainability scholarship concerns identification and specification of the alternative new culture contacting local culture. Evidence exists for tourism industry, universal tourist, and location/event-specific tourist culture. The biculturalism paradigm holds promise for researchers examining evolving cultural identity and integrity in response to mass tourism. In particular, confirmed constructs and scales simplify operationalization of tourism sustainability studies in terms of human impact and adjustment.

Keywords: biculturalism, cultural integrity, psychological and sociocultural adjustment, tourist culture

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Authors: Wu Liching

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Aim This case aims to discuss the pathogenesis, clinical manifestations and medical treatment of strokes caused by mitochondrial gene mutations. Methods Diagnosis of ischemic stroke caused by mitochondrial gene defect by means of "next-generation sequencing mitochondrial DNA gene variation detection", imaging examination, neurological examination, and medical history; this study took samples from the neurology ward of a medical center in northern Taiwan cases diagnosed with acute cerebral infarction as the research objects. Result This case is a 49-year-old married woman with a rare disease, mitochondrial gene mutation inducing ischemic stroke. She has severe hearing impairment and needs to use hearing aids, and has a history of diabetes. During the patient’s hospitalization, the blood test showed that serum Lactate: 7.72 mmol/L, Lactate (CSF) 5.9 mmol/L. Through the collection of relevant medical history, neurological evaluation showed changes in consciousness and cognition, slow response in language expression, and brain magnetic resonance imaging examination showed subacute bilateral temporal lobe infarction, which was an atypical type of stroke. The lineage DNA gene has m.3243A>G known pathogenic mutation point, and its heteroplasmic level is 24.6%. This pathogenic point is located in MITOMAP and recorded as Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like episodes (MELAS) , Leigh Syndrome and other disease-related pathogenic loci, this mutation is located in ClinVar and recorded as Pathogenic (dbSNP: rs199474657), so it is diagnosed as a case of stroke caused by a rare disease mitochondrial gene mutation. After medical treatment, there was no more seizure during hospitalization. After interventional rehabilitation, the patient's limb weakness, poor language function, and cognitive impairment have all improved significantly. Conclusion Mitochondrial disorders can also be associated with abnormalities in psychological, neurological, cerebral cortical function, and autonomic functions, as well as problems with internal medical diseases. Therefore, the differential diagnoses cover a wide range and are not easy to be diagnosed. After neurological evaluation, medical history collection, imaging and rare disease serological examination, atypical ischemic stroke caused by rare mitochondrial gene mutation was diagnosed. We hope that through this case, the diagnosis of rare disease mitochondrial gene variation leading to cerebral infarction will be more familiar to clinical medical staff, and this case report may help to improve the clinical diagnosis and treatment for patients with similar clinical symptoms in the future.

Keywords: acute stroke, MELAS, lactic acidosis, mitochondrial disorders

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Authors: Eleonora Di Salvo, Antonio Panebianco, Graziella Ziino

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Background: Vibrio parahaemolyticus is a human pathogen that is widely distributed in marine environments. It is frequently isolated from raw seafood, particularly shellfish. Consumption of raw or undercooked seafood contaminated with V. parahaemolyticus may lead to acute gastroenteritis. Vibrio spp. has excellent resistance to low temperatures so it can be found in frozen products for a long time. Recently, the viable but non-culturable state (VBNC) of bacteria has attracted great attention, and more than 85 species of bacteria have been demonstrated to be capable of entering this state. VBNC cells cannot grow in conventional culture medium but are viable and maintain metabolic activity, which may constitute an unrecognized source of food contamination and infection. Also V. parahaemolyticus could exist in VBNC state under nutrient starvation or low-temperature conditions. Aim: The aim of the present study was to optimize methods and investigate V. parahaemolyticus VBNC cells and their presence in frozen bivalve molluscs, regularly marketed. Materials and Methods: propidium monoazide (PMA) was integrated with real-time polymerase chain reaction (qPCR) targeting the tl gene to detect and quantify V. parahaemolyticus in the VBNC state. PMA-qPCR resulted highly specific to V. parahaemolyticus with a limit of detection (LOD) of 10-1 log CFU/mL in pure bacterial culture. A standard curve for V. parahaemolyticus cell concentrations was established with the correlation coefficient of 0.9999 at the linear range of 1.0 to 8.0 log CFU/mL. A total of 77 samples of frozen bivalve molluscs (35 mussels; 42 clams) were subsequently subjected to the qualitative (on alkaline phosphate buffer solution) and quantitative research of V. parahaemolyticus on thiosulfate-citrate-bile salts-sucrose (TCBS) agar (DIFCO) NaCl 2.5%, and incubation at 30°C for 24-48 hours. Real-time PCR was conducted on homogenate samples, in duplicate, with and without propidium monoazide (PMA) dye, and exposed for 45 min under halogen lights (650 W). Total DNA was extracted from cell suspension in homogenate samples according to bolliture protocol. The Real-time PCR was conducted with species-specific primers for V. parahaemolitycus. The RT-PCR was performed in a final volume of 20 µL, containing 10 µL of SYBR Green Mixture (Applied Biosystems), 2 µL of template DNA, 2 µL of each primer (final concentration 0.6 mM), and H2O 4 µL. The qPCR was carried out on CFX96 TouchTM (Bio-Rad, USA). Results: All samples were negative both to the quantitative and qualitative detection of V. parahaemolyticus by the classical culturing technique. The PMA-qPCR let us individuating VBNC V. parahaemolyticus in the 20,78% of the samples evaluated with a value between the Log 10-1 and Log 10-3 CFU/g. Only clams samples were positive for PMA-qPCR detection. Conclusion: The present research is the first evaluating PMA-qPCR assay for detection of VBNC V. parahaemolyticus in bivalve molluscs samples, and the used method was applicable to the rapid control of marketed bivalve molluscs. We strongly recommend to use of PMA-qPCR in order to identify VBNC forms, undetectable by the classic microbiological methods. A precise knowledge of the V.parahaemolyticus in a VBNC form is fundamental for the correct risk assessment not only in bivalve molluscs but also in other seafood.

Keywords: food safety, frozen bivalve molluscs, PMA dye, Real-time PCR, VBNC state, Vibrio parahaemolyticus

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Authors: Gyu-Dong Kim, Wuk-Jae Yoo, Sang-Youl Lee

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Composite structures offer numerous advantages over conventional structural systems in the form of higher specific stiffness and strength, lower life-cycle costs, and benefits such as easy installation and improved safety. Recently, there has been a considerable increase in the use of composites in engineering applications and as wraps for seismic upgrading and repairs. However, these composites deteriorate with time because of outdated materials, excessive use, repetitive loading, climatic conditions, manufacturing errors, and deficiencies in inspection methods. In particular, damaged fibers in a composite result in significant degradation of structural performance. In order to reduce the failure probability of composites in service, techniques to assess the condition of the composites to prevent continual growth of fiber damage are required. Condition assessment technology and nondestructive evaluation (NDE) techniques have provided various solutions for the safety of structures by means of detecting damage or defects from static or dynamic responses induced by external loading. A variety of techniques based on detecting the changes in static or dynamic behavior of isotropic structures has been developed in the last two decades. These methods, based on analytical approaches, are limited in their capabilities in dealing with complex systems, primarily because of their limitations in handling different loading and boundary conditions. Recently, investigators have introduced direct search methods based on metaheuristics techniques and artificial intelligence, such as genetic algorithms (GA), simulated annealing (SA) methods, and neural networks (NN), and have promisingly applied these methods to the field of structural identification. Among them, GAs attract our attention because they do not require a considerable amount of data in advance in dealing with complex problems and can make a global solution search possible as opposed to classical gradient-based optimization techniques. In this study, we propose an alternative damage-detection technique that can determine the degraded stiffness distribution of vibrating laminated composites made of Glass Fiber-reinforced Polymer (GFRP). The proposed method uses a modified form of the bivariate Gaussian distribution function to detect degraded stiffness characteristics. In addition, this study presents a method to detect the fiber property variation of laminated composite plates from the micromechanical point of view. The finite element model is used to study free vibrations of laminated composite plates for fiber stiffness degradation. In order to solve the inverse problem using the combined method, this study uses only first mode shapes in a structure for the measured frequency data. In particular, this study focuses on the effect of the interaction among various parameters, such as fiber angles, layup sequences, and damage distributions, on fiber-stiffness damage detection.

Keywords: stiffness detection, fiber damage, genetic algorithm, layup sequences

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Authors: Waseem Akram, Hafiz Azhar Ali Khan

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Unplanned urbanization together with change in life from simple to more technologically advanced style with flow of rural masses to urban areas has played a vital role in pilling loads of solid wastes in our environment. The cities and towns have expanded beyond boundaries. Even the uncontrolled population expansion has caused the overall environmental burden. Thus, today the indifference remains as one of the biggest trash that has come up due to the non-responsive behavior of the people. Everyday huge amount of solid waste is thrown in the streets, on the roads, parks, and in all those places that are frequently and often visited by the human beings. This behavior based response in many countries of the world has led to serious health concerns and environmental issues. Over 80% of our products that are sold in the market are packed in plastic bags. None of the bags are later recycled but simply become a permanent environment concern that flies, choke lines or are burnt and release toxic gases in the environment or form dumps of heaps. Lack of classification of the daily waste generated from houses and other places lead to worst clogging of the sewerage lines and formation of ponding areas which ultimately favor vector borne disease and sometimes become a cause of transmission of polio virus. Solid waste heaps were checked at different places of the cities. All of the wastes on visual assessments were classified into plastic bags, papers, broken plastic pots, clay pots, steel boxes, wrappers etc. All solid waste dumping sites in the cities and wastes that were thrown outside of the trash containers usually contained wrappers, plastic bags, and unconsumed food products. Insect populations seen in these sites included the house flies, bugs, cockroaches and mosquito larvae breeding in water filled wrappers, containers or plastic bags. The population of the mosquitoes, cockroaches and houseflies were relatively very high in dumping sites close to human population. This population has been associated with cases like dengue, malaria, dysentery, gastro and also to skin allergies during the monsoon and summer season. Thus, dumping of the huge amount of solid wastes in and near the residential areas results into serious environmental concerns, bad smell circulation, and health related issues. In some places, the same waste is burnt to get rid of mosquitoes through smoke which ultimately releases toxic material in the atmosphere. Therefore, a proper environmental strategy is needed to minimize environmental burden and promote concepts of recycled products and thus, reduce the disease burden.

Keywords: solid waste accumulation, disease burden, mosquitoes, vector borne diseases

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Authors: William Ho, Agus Wicaksana

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Anecdotal evidence in the last decade shows that the occurrence of disruptive events and uncertainties in the supply chain is increasing. The coupling of these events with the nature of an increasingly complex and interdependent business environment leads to devastating impacts that quickly propagate within and across organizations. For example, the recent COVID-19 pandemic increased the global supply chain disruption frequency by at least 20% in 2020 and is projected to have an accumulative cost of $13.8 trillion by 2024. This crisis raises attention to organizational resilience to weather business uncertainty. However, the concept has been criticized for being vague and lacking a consistent definition, thus reducing the significance of the concept for practice and research. This study is intended to solve that issue by providing a comprehensive review of the conceptualization, measurement, and antecedents of operational resilience that have been discussed in the supply chain risk management literature (SCRM). We performed a Scholarly Network Analysis, combining citation-based and text-based approaches, on 252 articles published from 2000 to 2021 in top-tier journals based on three parameters: AJG ranking and ABS ranking, UT Dallas and FT50 list, and editorial board review. We utilized a hybrid scholarly network analysis by combining citation-based and text-based approaches to understand the conceptualization, measurement, and antecedents of operational resilience in the SCRM literature. Specifically, we employed a Bibliographic Coupling Analysis in the research cluster formation stage and a Co-words Analysis in the research cluster interpretation and analysis stage. Our analysis reveals three major research clusters of resilience research in the SCRM literature, namely (1) supply chain network design and optimization, (2) organizational capabilities, and (3) digital technologies. We portray the research process in the last two decades in terms of the exemplar studies, problems studied, commonly used approaches and theories, and solutions provided in each cluster. We then provide a conceptual framework on the conceptualization and antecedents of resilience based on studies in these clusters and highlight potential areas that need to be studied further. Finally, we leverage the concept of abnormal operating performance to propose a new measurement strategy for resilience. This measurement overcomes the limitation of most current measurements that are event-dependent and focus on the resistance or recovery stage - without capturing the growth stage. In conclusion, this study provides a robust literature review through a scholarly network analysis that increases the completeness and accuracy of research cluster identification and analysis to understand conceptualization, antecedents, and measurement of resilience. It also enables us to perform a comprehensive review of resilience research in SCRM literature by including research articles published during the pandemic and connects this development with a plethora of articles published in the last two decades. From the managerial perspective, this study provides practitioners with clarity on the conceptualization and critical success factors of firm resilience from the SCRM perspective.

Keywords: supply chain risk management, organizational resilience, scholarly network analysis, systematic literature review

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Authors: Oluwafunmibi Omotayo Fasanya, Augustine Kena Adjei

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Background and Aims: This meta-analysis aimed to evaluate the effect of vitamin D supplementation on key metabolic and cardiovascular parameters, such as glycated hemoglobin (HbA1C), fasting blood sugar (FBS), low-density lipoprotein (LDL), high-density lipoprotein (HDL), systolic blood pressure (SBP), and total vitamin D levels in patients with Type 2 diabetes mellitus (T2DM). Methods: A systematic search was performed across databases, including PubMed, Scopus, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov, from January 1990 to January 2024. A total of 4,177 relevant studies were initially identified. Using an unsupervised K-means clustering algorithm, publications were grouped based on common text features. Maximum entropy classification was then applied to filter studies that matched a pre-identified training set of 139 potentially relevant articles. These selected studies were manually screened for relevance. A parallel manual selection of all initially searched studies was conducted for validation. The final inclusion of studies was based on full-text evaluation, quality assessment, and meta-regression models using random effects. Sensitivity analysis and publication bias assessments were also performed to ensure robustness. Results: The unsupervised K-means clustering algorithm grouped the patients based on their responses to vitamin D supplementation, using key biomarkers such as HbA1C, FBS, LDL, HDL, SBP, and total vitamin D levels. Two primary clusters emerged: one representing patients who experienced significant improvements in these markers and another showing minimal or no change. Patients in the cluster associated with significant improvement exhibited lower HbA1C, FBS, and LDL levels after vitamin D supplementation, while HDL and total vitamin D levels increased. The analysis showed that vitamin D supplementation was particularly effective in reducing HbA1C, FBS, and LDL within this cluster. Furthermore, BMI, weight gain, and disease duration were identified as factors that influenced cluster assignment, with patients having lower BMI and shorter disease duration being more likely to belong to the improvement cluster. Conclusion: The findings of this machine learning-assisted meta-analysis confirm that vitamin D supplementation can significantly improve glycemic control and reduce the risk of cardiovascular complications in T2DM patients. The use of automated screening techniques streamlined the process, ensuring the comprehensive evaluation of a large body of evidence while maintaining the validity of traditional manual review processes.

Keywords: HbA1C, T2DM, SBP, FBS

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Authors: Peter Kus, Anna Ostroverkh, Yurii Yakovlev, Yevheniia Lobko, Roman Fiala, Ivan Khalakhan, Vladimir Matolin

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Hydrogen economy is a concept of low-emission society which harvests most of its energy from renewable sources (e.g., wind and solar) and in case of overproduction, electrochemically turns the excess amount into hydrogen, which serves as an energy carrier. Proton exchange membrane water electrolyzers (PEMWE) are the backbone of this concept. By fast-response electricity to hydrogen conversion, the PEMWEs will not only stabilize the electrical grid but also provide high-purity hydrogen for variety of fuel cell powered devices, ranging from consumer electronics to vehicles. Wider commercialization of PEMWE technology is however hindered by high prices of noble metals which are necessary for catalyzing the redox reactions within the cell. Namely, platinum for hydrogen evolution reaction (HER), running on cathode, and iridium for oxygen evolution reaction (OER) on anode. Possible way of how to lower the loading of Pt and Ir is by using conductive high-surface nanostructures as catalyst supports in conjunction with thin-film catalyst deposition. The presented study discusses unconventional technique of membrane electron assembly (MEA) preparation. Noble metal catalysts (Pt and Ir) were magnetron sputtered in very low loadings onto the surface of porous sublayers (located on gas diffusion layer or directly on membrane), forming so to say localized three-phase boundary. Ultrasonically sprayed corrosion resistant TiC-based sublayer was used as a support material on anode, whereas magnetron sputtered nanostructured etched nitrogenated carbon (CNx) served the same role on cathode. By using this configuration, we were able to significantly decrease the amount of noble metals (to thickness of just tens of nanometers), while keeping the performance comparable to that of average state-of-the-art catalysts. Complex characterization of prepared supported catalysts includes in-cell performance and durability tests, electrochemical impedance spectroscopy (EIS) as well as scanning electron microscopy (SEM) imaging and X-ray photoelectron spectroscopy (XPS) analysis. Our research proves that magnetron sputtering is a suitable method for thin-film deposition of electrocatalysts. Tested set-up of thin-film supported anode and cathode catalysts with combined loading of just 120 ug.cm⁻² yields remarkable values of specific current. Described approach of thin-film low-loading catalyst deposition might be relevant when noble metal reduction is the topmost priority.

Keywords: hydrogen economy, low-loading catalyst, magnetron sputtering, proton exchange membrane water electrolyzer

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Authors: Leto Leandra, Guaitini Caterina, Agosti Anna, Del Vecchio Lorenzo, Guarrasi Valeria, Cirlini Martina, Chiancone Benedetta

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To the best of our knowledge, this study represents the first attempt to investigate the in vitro germination response of Rhus coriaria L., and its sprout chemical characterization. Rhus coriaria L., a species belonging to the Anacardiaceae family, is commonly called "sumac" and is cultivated, in different countries of the Mediterranean and the Middle East regions, to produce a spice with a sour taste, obtained from its dried and ground fruits. Moreover, since ancient times, many beneficial properties have been attributed to this plant that has been used, in the traditional medicine of several Asian countries, against various diseases, including liver and intestinal pathologies, ulcers and various inflammatory states. In the recent past, sumac was cultivated in the Southern regions of Italy to treat leather, but its cultivation was abandoned, and currently, sumac plants grow spontaneously in marginal areas. Recently, in Italy, the interest in this species has been growing again, thanks to its numerous properties; thus, it becomes imperative to deepen the knowledge of this plant. In this study, in order to set up an efficient in vitro seed germination protocol, sumac seeds collected from spontaneous plants grown in Sicily, an island in the South of Italy, were, firstly, subjected to different treatments, scarification (mechanical, physical and chemical), cold stratification and imbibition, to break their physical and physiological dormancy, then, treated seeds were in vitro cultured on media with different gibberellic acid (GA3) concentrations. Results showed that, without any treatment, only 5% of in vitro sown seeds germinated, while the germination percentage increased up to 19% after the mechanical scarification. A further significative improvement of germination percentages was recorded after the physical scarification, with (40.5%) or without (36.5%) 8 weeks of cold stratification, especially when seeds were sown on gibberellin enriched cultured media. Vitro-derived sumac sprouts, at different developmental stages, were chemically characterized, in terms of polyphenol and tannin content, as well as for their antioxidant activity, to evaluate this matrix as a potential novel food or as a source of bioactive compounds. Results evidenced how more developed sumac sprouts and, above all, their leaves are a wealthy source of polyphenols (78.4 GAE/g SS) and tannins (21.9 mg GAE/g SS), with marked antioxidant activity. The outcomes of this study will be of support the nursery sector and sumac growers in obtaining a higher number of plants in a shorter time; moreover, the sprout chemical characterization will contribute to the process of considering this matrix as a new source of bioactive compounds and tannins to be used in food and non-food sectors.

Keywords: bioactive compounds, germination pre-treatments, rhus coriaria l., tissue culture

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Authors: Leto Leandra, Guaitini Caterina, Agosti Anna, Del Vecchio Lorenzo, Guarrasi Valeria, Cirlini Martina, Chiancone Benedetta

Abstract:

To the best of our knowledge, this study represents the first attempt to investigate the in vitro germination response of Rhus coriaria L. and its sprout chemical characterization. Rhus coriaria L., a species belonging to the Anacardiaceae family, is commonly called "sumac” and is cultivated, in different countries of the Mediterranean and the Middle East regions, to produce a spice with a sour taste, obtained from its dried and ground fruits. Moreover, since ancient times, many beneficial properties have been attributed to this plant that has been used, in the traditional medicine of several Asian countries, against various diseases, including liver and intestinal pathologies, ulcers, and various inflammatory states. In the recent past, sumac was cultivated in the Southern regions of Italy to treat leather, but its cultivation was abandoned, and currently, sumac plants grow spontaneously in marginal areas. Recently, in Italy, the interest in this species has been growing again, thanks to its numerous properties; thus, it becomes imperative to deepen the knowledge of this plant. In this study, in order to set up an efficient in vitro seed germination protocol, sumac seeds collected from spontaneous plants grown in Sicily, an island in the South of Italy, were, firstly, subjected to different treatments, scarification (mechanical, physical and chemical), cold stratification and imbibition, to break their physical and physiological dormancy, then, treated seeds were in vitro cultured on media with different gibberellic acid (GA3) concentrations. Results showed that, without any treatment, only 5% of in vitro sown seeds germinated, while the germination percentage increased up to 19% after the mechanical scarification. A further significative improvement of germination percentages was recorded after the physical scarification, with (40.5%) or without (36.5%) 8 weeks of cold stratification, especially when seeds were sown on gibberellin enriched cultured media. Vitro-derived sumac sprouts, at different developmental stages, were chemically characterized, in terms of polyphenol and tannin content, as well as for their antioxidant activity, to evaluate this matrix as a potential novel food or as a source of bioactive compounds. Results evidenced how more developed sumac sprouts and, above all, their leaves are a wealthy source of polyphenols (78.4 GAE/g SS) and tannins (21.9 mg GAE/g SS), with marked antioxidant activity. The outcomes of this study will be of support the nursery sector and sumac growers in obtaining a higher number of plants in a shorter time; moreover, the sprout chemical characterization will contribute to the process of considering this matrix as a new source of bioactive compounds and tannins to be used in food and non-food sectors.

Keywords: bioactive compounds, germination pre-treatments, rhus coriaria l., tissue culture

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Authors: Rana Parween, Rob Marchant

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With the continued loss of global biodiversity despite the application of modern conservation techniques, it has become crucial to investigate non-conventional methods. Accelerated destruction of ecosystems due to altered land use, climate change, cultural and social change, necessitates the exploration of society-biodiversity attitudes and links. While the loss of species and their extinction is a well-known and well-documented process that attracts much-needed attention from researchers, academics, government and non-governmental organizations, the loss of traditional ecological knowledge and practices is more insidious and goes unnoticed. The growing availability of 'indirect experiences' such as the internet and media are leading to a disaffection towards nature and the 'Extinction of Experience'. Exacerbated by the lack of documentation of traditional practices and skills, there is the possibility for the 'extinction' of traditional practices and skills before they are fully recognized and captured. India, as a mega-biodiverse country, is also known for its historical conservation strategies entwined in traditional beliefs. Indigenous communities hold skillsets, knowledge, and traditions that have accumulated over multiple generations and may play an important role in conserving biodiversity today. This study explores the differences in knowledge and attitudes towards conserving biodiversity, of three different stakeholder groups living around Jim Corbett National Park, based on their age, traditions, and association with the protected area. A triangulation designed multi-strategy investigation collected qualitative and quantitative data through a questionnaire survey of village elders, the general public, and forest officers. Following an inductive approach to analyzing qualitative data, the thematic content analysis was followed. All coding and analysis were completed using NVivo 11. Although the village elders and some general public had vast amounts of traditional knowledge, most of it was related to animal husbandry and the medicinal value of plants. Village elders were unfamiliar with the concept of the term ‘biodiversity’ albeit their way of life and attitudes ensured that they care for the ecosystem without having the scientific basis underpinning biodiversity conservation. Inherently, village elders were keen to conserve nature; the superimposition of governmental policies without any tangible benefit or consultation was seen as detrimental. Alienating villagers and consequently the village elders who are the reservoirs of traditional knowledge would not only be damaging to the social network of the area but would also disdain years of tried and tested techniques held by the elders. Forest officers advocated for biodiversity and conservation education for women and children. Women, across all groups, when questioned about nature conservation, showed more interest in learning and participation. Biodiversity not only has an ethical and cultural value, but also plays a role in ecosystem function and, thus, provides ecosystem services and supports livelihoods. Therefore, underpinning and using traditional knowledge and incorporating them into programs of biodiversity conservation should be explored with a sense of urgency.

Keywords: biological diversity, mega-biodiverse countries, traditional ecological knowledge, society-biodiversity links

Procedia PDF Downloads 105

Authors: Samuel N. Forjuoh, Marcia G. Ory, Jaewoong Won, Samuel D. Towne, Suojin Wang, Chanam Lee

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The public health burden of obesity is well established as is the influence of physical activity (PA) on the health and wellness of individuals who are obese. This study examined the influence of selected demographic, health, and socioenvironmental factors on the walking behaviors of middle-aged and older overweight and obese adults. Online and paper surveys were administered to community-dwelling overweight and obese adults aged ≥ 50 years residing in four cities in central Texas and seen by a family physician in the primary care clinic from October 2013 to June 2014. Descriptive statistics were used to characterize participants’ anthropometric and demographic data as well as their health conditions and walking, socioenvironmental, and more broadly defined PA behaviors. Then Pearson chi-square tests were used to assess differences between participants who reported walking the recommended ≥ 150 minutes for any purpose in a typical week as a proxy to meeting the U.S. Centers for Disease Control and Prevention’s PA guidelines and those who did not. Finally, logistic regression was used to predict walking the recommended ≥ 150 minutes for any purpose, controlling for covariates. The analysis was conducted in 2016. Of the total sample (n=253, survey response rate of 6.8%), the majority were non-Hispanic white (81.7%), married (74.5%), male (53.5%), and reported an annual household income of ≥ $50,000 (65.7%). Approximately, half were employed (49.6%), or had at least a college degree (51.8%). Slightly more than 1 in 5 (n=57, 22.5%) reported walking the recommended ≥150 minutes for any purpose in a typical week. The strongest predictors of walking the recommended ≥ 150 minutes for any purpose in a typical week in adjusted analysis were related to education and a high favorable perception of the neighborhood environment. Compared to those with a high school diploma or some college, participants with at least a college degree were five times as likely to walk the recommended ≥ 150 minutes for any purpose (OR=5.55, 95% CI=1.79-17.25). Walking the recommended ≥ 150 minutes for any purpose was significantly associated with participants who disagreed that there were many distracted drivers (e.g., on the cell phone while driving) in their neighborhood (OR=4.08, 95% CI=1.47-11.36) and those who agreed that there are sidewalks or protected walkways (e.g., walking trails) in their neighborhood (OR=3.55, 95% CI=1.10-11.49). Those employed were less likely to walk the recommended ≥ 150 minutes for any purpose compared to those unemployed (OR=0.31, 95% CI=0.11-0.85) as were those who reported some difficulty walking for a quarter of a mile (OR=0.19, 95% CI=0.05-0.77). Other socio-environmental factors such as having care-giver responsibilities for elders, someone to walk with, or a dog in the household as well as Walk Score™ were not significantly associated with walking the recommended ≥ 150 minutes for any purpose in a typical week. Neighborhood perception appears to be an important factor associated with the walking behaviors of middle-aged and older overweight and obese individuals. Enhancing the neighborhood environment (e.g., providing walking trails) may promote walking among these individuals.

Keywords: determinants of walking, obesity, older adults, physical activity

Procedia PDF Downloads 259

Authors: Liang Zhao, Chongquan Zhong

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Introduction: According to statistics, people spend 80% to 90% of time indoor, so indoor air quality, either at home or in the office, greatly impacts the quality of life, health and work efficiency. Therefore, indoor air quality is very important to human activities. With the acceleration of urbanization, people are spending more time in indoor activity. The time in indoor environment, the living space, and the frequency interior decoration are all increasingly increased. However, housing decoration materials contain formaldehyde and other harmful substances, causing environmental and air quality problems, which have brought serious damage to countless families and attracted growing attention. According to World Health Organization statistics, the indoor environments in more than 30% of buildings in China are polluted by poisonous and harmful gases. Indoor pollution has caused various health problems, and these widespread public health problems can lead to respiratory diseases. Long-term inhalation of low-concentration formaldehyde would cause persistent headache, insomnia, weakness, palpitation, weight loss and vomiting, which are serious impacts on human health and safety. On the other hand, as for offices, some surveys show that good indoor air quality helps to enthuse the staff and improve the work efficiency by 2%-16%. Therefore, people need to further understand the living and working environments. There is a need for easy-to-use indoor environment monitoring instruments, with which users only have to power up and monitor the environmental parameters. The corresponding real-time data can be displayed on the screen for analysis. Environment monitoring should have the sensitive signal alarm function and send alarm when harmful gases such as formaldehyde, CO, SO2, are excessive to human body. System design: According to the monitoring requirements of various gases, temperature and humidity, we designed a portable, light, real-time and accurate monitor for various environmental parameters, including temperature, humidity, formaldehyde, methane, and CO. This monitor will generate an alarm signal when a target is beyond the standard. It can conveniently measure a variety of harmful gases and provide the alarm function. It also has the advantages of small volume, convenience to carry and use. It has a real-time display function, outputting the parameters on the LCD screen, and a real-time alarm function. Conclusions: This study is focused on the research and development of a portable parameter monitoring instrument for indoor environment. On the platform of an STM32 development board, the monitored data are collected through an external sensor. The STM32 platform is for data acquisition and processing procedures, and successfully monitors the real-time temperature, humidity, formaldehyde, CO, methane and other environmental parameters. Real-time data are displayed on the LCD screen. The system is stable and can be used in different indoor places such as family, hospital, and office. Meanwhile, the system adopts the idea of modular design and is superior in transplanting. The scheme is slightly modified and can be used similarly as the function of a monitoring system. This monitor has very high research and application values.

Keywords: indoor air quality, gas concentration detection, embedded system, sensor

Procedia PDF Downloads 255

Authors: Md Kamrul Hassan

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Adaptation interventions are the common response to manage the vulnerabilities of climate change. The nature of adaptation intervention depends on the degree of vulnerability and the capacity of a society. The coping interventions can take the form of hard adaptation – utilising technologies and capital goods like dykes, embankments, seawalls, and/or soft adaptation – engaging knowledge and information sharing, capacity building, policy and strategy development, and innovation. Hard adaptation is quite capital intensive but provides immediate relief from climate change vulnerabilities. This type of adaptation is not real development, as the investment for the adaptation cannot improve the performance – just maintain the status quo of a social or ecological system, and often lead to maladaptation in the long-term. Maladaptation creates a two-way loss for a society – interventions bring further vulnerability on top of the existing vulnerability and investment for getting rid of the consequence of interventions. Hard adaptation is popular to the vulnerable groups, but it focuses so much on the immediate solution and often ignores the environmental issues and future risks of climate change. On the other hand, soft adaptation is education oriented where vulnerable groups learn how to live with climate change impacts. Soft adaptation interventions build the capacity of vulnerable groups through training, innovation, and support, which might enhance the resilience of a system. In consideration of long-term sustainability, soft adaptation can contribute more to resilience than hard adaptation. Taking a developing society as the study context, this study aims to investigate and understand the effectiveness of the adaptation interventions of the coastal community of Sundarbans mangrove forest in Bangladesh. Applying semi-structured interviews with a range of Sundarbans stakeholders including community residents, tourism demand-supply side stakeholders, and conservation and management agencies (e.g., Government, NGOs and international agencies) and document analysis, this paper reports several key insights regarding climate change adaptation. Firstly, while adaptation interventions may offer a short-term to medium-term solution to climate change vulnerabilities, interventions need to be revised for long-term sustainability. Secondly, soft adaptation offers advantages in terms of resilience in a rapidly changing environment, as it is flexible and dynamic. Thirdly, there is a challenge to communicate to educate vulnerable groups to understand more about the future effects of hard adaptation interventions (and the potential for maladaptation). Fourthly, hard adaptation can be used if the interventions do not degrade the environmental balance and if the investment of interventions does not exceed the economic benefit of the interventions. Overall, the goal of an adaptation intervention should be to enhance the resilience of a social or ecological system so that the system can with stand present vulnerabilities and future risks. In order to be sustainable, adaptation interventions should be designed in such way that those can address vulnerabilities and risks of climate change in a long-term timeframe.

Keywords: adaptation, climate change, maladaptation, resilience, Sundarbans, sustainability, vulnerability

Procedia PDF Downloads 194

Authors: Sylvia Chan-Olmsted, Lisa-Charlotte Wolter

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With the continuous proliferation of media platforms, there have been tremendous changes in media consumption behaviors. From the perspective of sports sponsorship, while there is now a multitude of platforms to create brand associations, the changing media landscape and shift of message control also mean that sports sponsors will have to take into account the nature of and consumer responses toward these emerging digital media to devise effective marketing strategies. Utilizing the personal interview methodology, this study is qualitative and exploratory in nature. A total of 18 experts from European and American academics, sports marketing industry, and sports leagues/teams were interviewed to address three main research questions: 1) What are the major changes in digital technologies that are relevant to sports sponsorship; 2) How have digital media influenced the channels and platforms of sports sponsorship; and 3) How have these technologies affected the goals, strategies, and measurement of sports sponsorship. The study found that sports sponsorship has moved from consumer engagement, engagement measurement, and consequences of engagement on brand behaviors to micro-targeting one on one, engagement by context, time, and space, and activation and leveraging based on tracking and databases. From the perspective of platforms and channels, the use of mobile devices is prominent during sports content consumption. Increasing multiscreen media consumption means that sports sponsors need to optimize their investment decisions in leagues, teams, or game-related content sources, as they need to go where the fans are most engaged in. The study observed an imbalanced strategic leveraging of technology and digital infrastructure. While sports leagues have had less emphasis on brand value management via technology, sports sponsors have been much more active in utilizing technologies like mobile/LBS tools, big data/user info, real-time marketing and programmatic, and social media activation. Regardless of the new media/platforms, the study found that integration and contextualization are the two essential means of improving sports sponsorship effectiveness through technology. That is, how sponsors effectively integrate social media/mobile/second screen into their existing legacy media sponsorship plan so technology works for the experience/message instead of distracting fans. Additionally, technological advancement and attention economy amplify the importance of consumer data gathering, but sports consumer data does not mean loyalty or engagement. This study also affirms the benefit of digital media as they offer viral and pre-event activations through storytelling way before the actual event, which is critical for leveraging brand association before and after. That is, sponsors now have multiple opportunities and platforms to tell stories about their brands for longer time period. In summary, digital media facilitate fan experience, access to the brand message, multiplatform/channel presentations, storytelling, and content sharing. Nevertheless, rather than focusing on technology and media, today’s sponsors need to define what they want to focus on in terms of content themes that connect with their brands and then identify the channels/platforms. The big challenge for sponsors is to play to the venues/media’s specificity and its fit with the target audience and not uniformly deliver the same message in the same format on different platforms/channels.

Keywords: digital media, mobile media, social media, technology, sports sponsorship

Procedia PDF Downloads 294

Authors: Hamed Yaghoubi, Esmaeil Salahi, Fateme Taati

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The effective shear and bulk viscosity, as well as dynamic viscosity, describe the rheological properties of the ceramic body during the liquid phase sintering process. The rheological parameters depend on the physical and thermomechanical characteristics of the material such as relative density, temperature, grain size, and diffusion coefficient and activation energy. The main goal of this research is to acquire a comprehensive understanding of the response of an incompressible viscose ceramic material during liquid phase sintering process such as stress-strain relations, sintering and hydrostatic stress, the prediction of anisotropic shrinkage and heterogeneous densification as a function of sintering time by including the simultaneous influence of gravity field, and frictional force. After raw materials analysis, the standard hard porcelain mixture as a ceramic body was designed and prepared. Three different experimental configurations were designed including midpoint deflection, sinter bending, and free sintering samples. The numerical method for the ceramic specimens during the liquid phase sintering process are implemented in the CREEP user subroutine code in ABAQUS. The numerical-experimental procedure shows the anisotropic behavior, the complete difference in spatial displacement through three directions, the incompressibility for ceramic samples during the sintering process. The anisotropic shrinkage factor has been proposed to investigate the shrinkage anisotropy. It has been shown that the shrinkage along the normal axis of casting sample is about 1.5 times larger than that of casting direction, the gravitational force in pyroplastic deformation intensifies the shrinkage anisotropy more than the free sintering sample. The lowest and greatest equivalent creep strain occurs at the intermediate zone and around the central line of the midpoint distorted sample, respectively. In the sinter bending test sample, the equivalent creep strain approaches to the maximum near the contact area with refractory support. The inhomogeneity in Von-Misses, pressure, and principal stress intensifies the relative density non-uniformity in all samples, except in free sintering one. The symmetrical distribution of stress around the center of free sintering sample, cause to hinder the pyroplastic deformations. Densification results confirmed that the effective bulk viscosity was well-defined with relative density values. The stress analysis confirmed that the sintering stress is more than the hydrostatic stress from start to end of sintering time so, from both theoretically and experimentally point of view, the sintering process occurs completely.

Keywords: anisotropic shrinkage, ceramic material, liquid phase sintering process, rheological properties, numerical-experimental procedure

Procedia PDF Downloads 341

Authors: Anele Horn, Amanda Van Eeden

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The emphasis on the challenges posed by continued urbanisation, especially in developing countries has resulted in urban sprawl often researched and analysed in metropolitan urban areas, but rarely in small and medium towns. Consequently, there exists no comparative instrument between the proportional extent of urban sprawl in metropolitan areas measured against that of small and medium towns. This research proposes an Urban Sprawl Index as a possible tool to comparatively analyse the extent of urban sprawl between cities and towns of different sizes. The index can also be used over the longer term by authorities developing spatial policy to track the success or failure of specific tools intended to curb urban sprawl. In South Africa, as elsewhere in the world, the last two decades witnessed a proliferation of legislation and spatial policies to limit urban sprawl and contain the physical expansion and development of urban areas, but the measurement of the successes or failures of these instruments intending to curb expansive land development has remained a largely unattainable goal, largely as a result of the absence of an appropriate measure of proportionate comparison. As a result of the spatial political history of Apartheid, urban areas acquired a spatial form that contributed to the formation of single-core cities with far reaching and wide-spreading peripheral development, either in the form of affluent suburbs or as a result of post-Apartheid programmes such as the Reconstruction and Development Programme (1995) which, in an attempt to assist the immediate housing shortage, favoured the establishment of single dwelling residential units for low income communities on single plots on affordable land at the urban periphery. This invariably contributed to urban sprawl and even though this programme has since been abandoned, the trend towards low density residential development continues. The research area is the Western Cape Province in South Africa, which in all aspects exhibit the spatial challenges described above. In academia and popular media the City of Cape Town (the only Metropolitan authority in the province) has received the lion’s share of focus in terms of critique on urban development and spatial planning, however, the smaller towns and cities in the Western Cape arguably received much less public attention and were spared the naming and shaming of being unsustainable urban areas in terms of land consumption and physical expansion. The Urban Sprawl Index for the Western Cape (USIWC) put forward by this research enables local authorities in the Western Cape Province to measure the extent of urban sprawl proportionately and comparatively to other cities in the province, thereby acquiring a means of measuring the success of the spatial instruments employed to limit urban expansion and inefficient land consumption. In development of the USIWC the research made use of satellite data for reference years 2001 and 2011 and population growth data extracted from the national census, also for base years 2001 and 2011.

Keywords: urban sprawl, index, Western Cape, South Africa

Procedia PDF Downloads 329

Authors: Natalia Caldeira De Carvalho, Tassia Batista Pessato, Luis Gustavo R. Fernandes, Ricardo L. Zollner, Flavia Maria Netto

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Protein hydrolysates are ingredients of enteral diets and hypoallergenic formulas. Enzymatic hydrolysis is the most commonly used method for reducing the antigenicity of milk protein. The antigenicity and physicochemical characteristics of the protein hydrolysates depend on the reaction parameters. Among them, pH has been pointed out as of the major importance. Hydrolysis reaction in laboratory scale is commonly carried out under controlled pH (pH-stat). However, from the industrial point of view, controlling pH during hydrolysis reaction may be infeasible. This study evaluated the impact of pH control on the physicochemical properties and antigenicity of the hydrolysates of whey proteins with Alcalase. Whey protein isolate (WPI) solutions containing 3 and 7 % protein (w/v) were hydrolyzed with Alcalase 50 and 100 U g-1 protein at 60°C for 180 min. The reactions were carried out under controlled and uncontrolled pH conditions. Hydrolyses performed under controlled pH (pH-stat) were initially adjusted and maintained at pH 8.5. Hydrolyses carried out without pH control were initially adjusted to pH 8.5. Degree of hydrolysis (DH) was determined by OPA method, peptides profile was evaluated by HPLC-RP, and molecular mass distribution by SDS-PAGE/Tricine. The residual α-lactalbumin (α-La) and β-lactoglobulin (β-Lg) concentrations were determined using commercial ELISA kits. The specific IgE and IgG binding capacity of hydrolysates was evaluated by ELISA technique, using polyclonal antibodies obtained by immunization of female BALB/c mice with α-La, β-Lg and BSA. In hydrolysis under uncontrolled pH, the pH dropped from 8.5 to 7.0 during the first 15 min, remaining constant throughout the process. No significant difference was observed between the DH of the hydrolysates obtained under controlled and uncontrolled pH conditions. Although all hydrolysates showed hydrophilic character and low molecular mass peptides, hydrolysates obtained with and without pH control exhibited different chromatographic profiles. Hydrolysis under uncontrolled pH released, predominantly, peptides between 3.5 and 6.5 kDa, while hydrolysis under controlled pH released peptides smaller than 3.5 kDa. Hydrolysis with Alcalase under all conditions studied decreased by 99.9% the α-La and β-Lg concentrations in the hydrolysates detected by commercial kits. In general, β-Lg concentrations detected in the hydrolysates obtained under uncontrolled pH were significantly higher (p<0.05) than those detected in hydrolysates produced with pH control. The anti-α-La and anti-β-Lg IgE and IgG responses to all hydrolysates decreased significantly compared to WPI. Levels of specific IgE and IgG to the hydrolysates were below 25 and 12 ng ml-1, respectively. Despite the differences in peptide composition and α-La and β-Lg concentrations, no significant difference was found between IgE and IgG binding capacity of hydrolysates obtained with or without pH control. These results highlight the impact of pH on the hydrolysates characteristics and their concentrations of antigenic protein. Divergence between the antigen detection by commercial ELISA kits and specific IgE and IgG binding response was found in this study. This result shows that lower protein detection does not imply in lower protein antigenicity. Thus, the use of commercial kits for allergen contamination analysis should be cautious.

Keywords: allergy, enzymatic hydrolysis, milk protein, pH conditions, physicochemical characteristics

Procedia PDF Downloads 302

Authors: N. B. Chandrakala

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Domestic violence is one of the most under-reported crimes. Problem with domestic violence is that it is not even considered as abuse in many parts of the world especially certain parts of Asia, Africa and Middle East. It is viewed as “doing the needful”. Domestic violence could be in form of emotional harassment, physical injury or psychological abuse perpetrated by one of the family members to another. It is a worldwide phenomenon mainly targeting women. The acts of violence have terrible negative impact on women. It is also an infringement of women’s rights and can be safely termed as human rights abuse. In cases pertaining to domestic violence, male adults often misuses his authority and power to control another using physical or psychological means. Violence and other forms of abuse are common in domestic violence. Sexual assaults, molestation and battering are common in these cases. Domestic violence is a human rights issue and a serious deterrent to development. Domestic violence could also take place in subtle forms like making the person feel worthless or not giving the victims any personal space or freedom. The problematic aspect is cases of domestic violence are very rarely reported. The majority of the victims are women but children are also made to suffer silently. They are abused and neglected. Their innocent minds are adversely affected with the incidents of domestic violence. According to a report by World Health Organization (WHO), sexual trafficking, female feticide, dowry death, public humiliation and physical torture are some of the most common forms of domestic violence against Indian women. Such acts belie our growth and claim as an economic superpower. It is ironic that we claim to be one of the most rapidly advancing countries in the world and yet we have done hardly anything of note against social hazards like domestic violence. Laws are not that stringent when it comes to reporting acts of domestic violence. Even if the report is filed it turns out to be a long drawn process and not every victim has that much resource to fight till the end. It is also a social taboo to make your family matters public. The big challenge in front now is to enforce it in true sense. Steps that are actually needed; tough laws against domestic violence, speedy execution and change in the mindset of society only then we can expect to have some improvement in such inhuman cases. An effective response to violence must be multi-sectoral; addressing the immediate practical needs of women experiencing abuse; providing long-term follow up and assistance; and focusing on changing those cultural norms, attitudes and legal provisions that promote the acceptance of and even encourage violence against women, and undermine women's enjoyment of their full human rights and freedoms. Hence the responses to the problem must be based on integrated approach. The effectiveness of measures and initiatives will depend on coherence and coordination associated with their design and implementation.

Keywords: domestic violence, human rights, sexual assaults, World Health Organization

Procedia PDF Downloads 542

Authors: Malek Miladi, Miguel Vegara, Maria Perez-Infantes, Khaled Mohamed Ramadan, Antonio Ruiz-Canales, Damaris Nunez-Gomez

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Coffee is the second consumed commodity worldwide, yet it also generates colossal waste. Proper management of coffee waste is proposed by converting them into products with higher added value to achieve sustainability of the economic and ecological footprint and protect the environment. Based on this, a study looking at the recovery of coffee waste is becoming more relevant in recent decades. Spent coffee grounds (SCG's) resulted from brewing coffee represents the major waste produced among all coffee industry. The fact that SCGs has no economic value be abundant in nature and industry, do not compete with agriculture and especially its high oil content (between 7-15% from its total dry matter weight depending on the coffee varieties, Arabica or Robusta), encourages its use as a sustainable feedstock for bio-oil production. The bio-oil extraction is a crucial step towards biodiesel production by the transesterification process. However, conventional methods used for oil extraction are not recommended due to their high consumption of energy, time, and generation of toxic volatile organic solvents. Thus, finding a sustainable, economical, and efficient extraction technique is crucial to scale up the process and to ensure more environment-friendly production. Under this perspective, the aim of this work was the statistical study to know an efficient strategy for oil extraction by n-hexane using indirect sonication. The coffee waste mixed Arabica and Robusta, which was used in this work. The temperature effect, sonication time, and solvent-to-solid ratio on the oil yield were statistically investigated as dependent variables by Central Composite Rotatable Design (CCRD) 23. The results were analyzed using STATISTICA 7 StatSoft software. The CCRD showed the significance of all the variables tested (P < 0.05) on the process output. The validation of the model by analysis of variance (ANOVA) showed good adjustment for the results obtained for a 95% confidence interval, and also, the predicted values graph vs. experimental values confirmed the satisfactory correlation between the model results. Besides, the identification of the optimum experimental conditions was based on the study of the surface response graphs (2-D and 3-D) and the critical statistical values. Based on the CCDR results, 29 ºC, 56.6 min, and solvent-to-solid ratio 16 were the better experimental conditions defined statistically for coffee waste oil extraction using n-hexane as solvent. In these conditions, the oil yield was >9% in all cases. The results confirmed the efficiency of using an ultrasound bath in extracting oil as a more economical, green, and efficient way when compared to the Soxhlet method.

Keywords: coffee waste, optimization, oil yield, statistical planning

Procedia PDF Downloads 119

Authors: Diane Ghanem, Oscar Covarrubias, Michael Raad, Dawn LaPorte, Babar Shafiq

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Introduction: Standardized exams have long been considered a cornerstone in measuring cognitive competency and academic achievement. Their fixed nature and predetermined scoring methods offer a consistent yardstick for gauging intellectual acumen across diverse demographics. Consequently, the performance of artificial intelligence (AI) in this context presents a rich, yet unexplored terrain for quantifying AI's understanding of complex cognitive tasks and simulating human-like problem-solving skills. Publicly available AI language models such as ChatGPT have demonstrated utility in text generation and even problem-solving when provided with clear instructions. Amidst this transformative shift, the aim of this study is to assess ChatGPT’s performance on the orthopaedic surgery in-training examination (OITE). Methods: All 213 OITE 2021 web-based questions were retrieved from the AAOS-ResStudy website. Two independent reviewers copied and pasted the questions and response options into ChatGPT Plus (version 4.0) and recorded the generated answers. All media-containing questions were flagged and carefully examined. Twelve OITE media-containing questions that relied purely on images (clinical pictures, radiographs, MRIs, CT scans) and could not be rationalized from the clinical presentation were excluded. Cohen’s Kappa coefficient was used to examine the agreement of ChatGPT-generated responses between reviewers. Descriptive statistics were used to summarize the performance (% correct) of ChatGPT Plus. The 2021 norm table was used to compare ChatGPT Plus’ performance on the OITE to national orthopaedic surgery residents in that same year. Results: A total of 201 were evaluated by ChatGPT Plus. Excellent agreement was observed between raters for the 201 ChatGPT-generated responses, with a Cohen’s Kappa coefficient of 0.947. 45.8% (92/201) were media-containing questions. ChatGPT had an average overall score of 61.2% (123/201). Its score was 64.2% (70/109) on non-media questions. When compared to the performance of all national orthopaedic surgery residents in 2021, ChatGPT Plus performed at the level of an average PGY3. Discussion: ChatGPT Plus is able to pass the OITE with a satisfactory overall score of 61.2%, ranking at the level of third-year orthopaedic surgery residents. More importantly, it provided logical reasoning and justifications that may help residents grasp evidence-based information and improve their understanding of OITE cases and general orthopaedic principles. With further improvements, AI language models, such as ChatGPT, may become valuable interactive learning tools in resident education, although further studies are still needed to examine their efficacy and impact on long-term learning and OITE/ABOS performance.

Keywords: artificial intelligence, ChatGPT, orthopaedic in-training examination, OITE, orthopedic surgery, standardized testing

Procedia PDF Downloads 89

Authors: Kusno Kamil, Andi Asni, Sungkono

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According to a report of the World Food and Agriculture Agency (FAO): the post-harvest fish losses in Indonesia reaches 30 percent from 170 trillion rupiahs of marine fisheries reserves, then the potential loss reaches 51 trillion rupiahs (end of 2016 data). This condition is caused by traditionally vulnerable fish catches damaged due to disruption of the cold chain of preservation. The physical and chemical changes in fish flesh increase rapidly, especially if exposed to the scorching heat in the middle of the sea, exacerbated by the low awareness of catch hygiene; many unclean catches which contain blood are often treated without special attention and mixed with freshly caught fish, thereby increasing the potential for faster fish spoilage. This background encourages research on traditional fisherman catch preservation methods that aim to find the best and most affordable methods and/or combinations of fish preservation methods so that they can help fishermen increase their fishing duration without worrying that their catch will be damaged, thereby reducing their economic value when returning to the beach to sell their catches. This goal is expected to be achieved through experimental methods of treatment of fresh fish catches in containers with the addition of anti-bacterial copper, liquid smoke solution, and the use of vacuum containers. The other three treatments combined the three previous treatment variables with an electrically powered cooler (temperature 0~4 ᵒC). As a control specimen, the untreated fresh fish (placed in the open air and in the refrigerator) were also prepared for comparison for 1, 3, and 6 days. To test the level of freshness of fish for each treatment, physical observations were used, which were complemented by tests for bacterial content in a trusted laboratory. The content of copper (Cu) in fish meat (which is suspected of having a negative impact on consumers) was also part of the examination on the 6th day of experimentation. The results of physical observations on the test specimens (organoleptic method) showed that preservation assisted by the use of coolers was still better for all treatment variables. The specimens, without cooling, sequentially showed that the best preservation effectiveness was the addition of copper plates, the use of vacuum containers, and then liquid smoke immersion. Especially for liquid smoke, soaking for 6 days of preservation makes the fish meat soft and easy to crumble, even though it doesn't have a bad odor. The visual observation was then complemented by the results of testing the amount of growth (or retardation) of putrefactive bacteria in each treatment of test specimens within similar observation periods. Laboratory measurements report that the minimum amount of putrefactive bacteria achieved by preservation treatment combining cooler with liquid smoke (sample A+), then cooler only (D+), copper layer inside cooler (B+), vacuum container inside cooler (C+), respectively. Other treatments in open air produced a hundred times more putrefactive bacteria. In addition, treatment of the copper layer contaminated the preserved fresh fish more than a thousand times bigger compared to the initial amount, from 0.69 to 1241.68 µg/g.

Keywords: fish, preservation, traditional, fishermen, boat

Procedia PDF Downloads 69

Authors: Tomasz Stenzel, Daria Dziewulska, Ewa Łukaszuk, Joy Custer, Simona Kraberger, Arvind Varsani

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Viral diseases, especially those leading to impairment of the immune system, are among the most important problems in avian pathology. However, there is not much data available on this subject other than commercial poultry bird species. Recently, increasing attention has been paid to racing pigeons, which have been refined for many years in terms of their ability to return to their place of origin. Currently, these birds are used for races at distances from 100 to 1000 km, and winning pigeons are highly valuable. The rearing system of racing pigeons contradicts the principles of biosecurity, as birds originating from various breeding facilities are commonly transported and reared in “One Loft Race” (OLR) facilities. This favors the spread of multiple infections and provides conditions for the development of novel variants of various pathogens through recombination. One of the most significant viruses occurring in this avian species is the pigeon circovirus (PiCV), which is detected in ca. 70% of pigeons. Circoviruses are characterized by vast genetic diversity which is due to, among other things, the recombination phenomenon. It consists of an exchange of fragments of genetic material among various strains of the virus during the infection of one organism. The rate and intensity of the development of PiCV recombinants have not been determined so far. For this reason, an experiment was performed to investigate the frequency of development of novel PiCV recombinants in racing pigeons kept in OLR-type conditions. 15 racing pigeons originating from 5 different breeding facilities, subclinically infected with various PiCV strains, were housed in one room for eight weeks, which was supposed to mimic the conditions of OLR rearing. Blood and swab samples were collected from birds every seven days to recover complete PiCV genomes that were amplified through Rolling Circle Amplification (RCA), cloned, sequenced, and subjected to bioinformatic analyses aimed at determining the genetic diversity and the dynamics of recombination phenomenon among the viruses. In addition, virus shedding rate/level of viremia, expression of the IFN-γ and interferon-related genes, and anti-PiCV antibodies were determined to enable the complete analysis of the course of infection in the flock. Initial results have shown that 336 full PiCV genomes were obtained, exhibiting nucleotide similarity ranging from 86.6 to 100%, and 8 of those were recombinants originating from viruses of different lofts of origin. The first recombinant appeared after seven days of experiment, but most of the recombinants appeared after 14 and 21 days of joint housing. The level of viremia and virus shedding was the highest in the 2nd week of the experiment and gradually decreased to the end of the experiment, which partially corresponded with Mx 1 gene expression and antibody dynamics. The results have shown that the OLR pigeon-rearing system could play a significant role in spreading infectious agents such as circoviruses and contributing to PiCV evolution through recombination. Therefore, it is worth considering whether a popular gambling game such as pigeon racing is sensible from both animal welfare and epidemiological point of view.

Keywords: pigeon circovirus, recombination, evolution, one loft race

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Authors: Nirjhar Dhang, S. Vinay Kumar

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Concrete is a non-homogeneous mix of coarse aggregates, sand, cement, air-voids and interfacial transition zone (ITZ) around aggregates. Adoption of these complex structures and material properties in numerical simulation would lead us to better understanding and design of concrete. In this work, the mesoscale model of concrete has been prepared from X-ray computerized tomography (CT) image. These images are converted into computer model and numerically simulated using commercially available finite element software. The mesoscale models are simulated under the influence of compressive displacement. The effect of shape and distribution of aggregates, continuous and discrete ITZ thickness, voids, and variation of mortar strength has been investigated. The CT scan of concrete cube consists of series of two dimensional slices. Total 49 slices are obtained from a cube of 150mm and the interval of slices comes approximately 3mm. In CT scan images, the same cube can be CT scanned in a non-destructive manner and later the compression test can be carried out in a universal testing machine (UTM) for finding its strength. The image processing and extraction of mortar and aggregates from CT scan slices are performed by programming in Python. The digital colour image consists of red, green and blue (RGB) pixels. The conversion of RGB image to black and white image (BW) is carried out, and identification of mesoscale constituents is made by putting value between 0-255. The pixel matrix is created for modeling of mortar, aggregates, and ITZ. Pixels are normalized to 0-9 scale considering the relative strength. Here, zero is assigned to voids, 4-6 for mortar and 7-9 for aggregates. The value between 1-3 identifies boundary between aggregates and mortar. In the next step, triangular and quadrilateral elements for plane stress and plane strain models are generated depending on option given. Properties of materials, boundary conditions, and analysis scheme are specified in this module. The responses like displacement, stresses, and damages are evaluated by ABAQUS importing the input file. This simulation evaluates compressive strengths of 49 slices of the cube. The model is meshed with more than sixty thousand elements. The effect of shape and distribution of aggregates, inclusion of voids and variation of thickness of ITZ layer with relation to load carrying capacity, stress-strain response and strain localizations of concrete have been studied. The plane strain condition carried more load than plane stress condition due to confinement. The CT scan technique can be used to get slices from concrete cores taken from the actual structure, and the digital image processing can be used for finding the shape and contents of aggregates in concrete. This may be further compared with test results of concrete cores and can be used as an important tool for strength evaluation of concrete.

Keywords: concrete, image processing, plane strain, interfacial transition zone

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Authors: Duncan Wallace, M-Tahar Kechadi

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In recent years, Machine Learning (ML) approaches have been successfully applied to an analysis of patient symptom data in the context of disease diagnosis, at least where such data is well codified. However, much of the data present in Electronic Health Records (EHR) are unlikely to prove suitable for classic ML approaches. Furthermore, as scores of data are widely spread across both hospitals and individuals, a decentralized, computationally scalable methodology is a priority. The focus of this paper is to develop a method to predict outliers in an out-of-hours healthcare provision center (OOHC). In particular, our research is based upon the early identification of patients who have underlying conditions which will cause them to repeatedly require medical attention. OOHC act as an ad-hoc delivery of triage and treatment, where interactions occur without recourse to a full medical history of the patient in question. Medical histories, relating to patients contacting an OOHC, may reside in several distinct EHR systems in multiple hospitals or surgeries, which are unavailable to the OOHC in question. As such, although a local solution is optimal for this problem, it follows that the data under investigation is incomplete, heterogeneous, and comprised mostly of noisy textual notes compiled during routine OOHC activities. Through the use of Deep Learning methodologies, the aim of this paper is to provide the means to identify patient cases, upon initial contact, which are likely to relate to such outliers. To this end, we compare the performance of Long Short-Term Memory, Gated Recurrent Units, and combinations of both with Convolutional Neural Networks. A further aim of this paper is to elucidate the discovery of such outliers by examining the exact terms which provide a strong indication of positive and negative case entries. While free-text is the principal data extracted from EHRs for classification, EHRs also contain normalized features. Although the specific demographical features treated within our corpus are relatively limited in scope, we examine whether it is beneficial to include such features among the inputs to our neural network, or whether these features are more successfully exploited in conjunction with a different form of a classifier. In this section, we compare the performance of randomly generated regression trees and support vector machines and determine the extent to which our classification program can be improved upon by using either of these machine learning approaches in conjunction with the output of our Recurrent Neural Network application. The output of our neural network is also used to help determine the most significant lexemes present within the corpus for determining high-risk patients. By combining the confidence of our classification program in relation to lexemes within true positive and true negative cases, with an inverse document frequency of the lexemes related to these cases, we can determine what features act as the primary indicators of frequent-attender and non-frequent-attender cases, providing a human interpretable appreciation of how our program classifies cases.

Keywords: artificial neural networks, data-mining, machine learning, medical informatics

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Authors: A. Chávez, A. Rodríguez, F. Pinzón

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Society is concerned about measures of environmental, economic and social impacts generated in the solid waste disposal. These places of confinement, also known as landfills, are locations where problems of pollution and damage to human health are reduced. They are technically designed and operated, using engineering principles, storing the residue in a small area, compact it to reduce volume and covering them with soil layers. Problems preventing liquid (leachate) and gases produced by the decomposition of organic matter. Despite planning and site selection for disposal, monitoring and control of selected processes, remains the dilemma of the leachate as extreme concentration of pollutants, devastating soil, flora and fauna; aggressive processes requiring priority attention. A biological technology is the activated sludge system, used for tributaries with high pollutant loads. Since transforms biodegradable dissolved and particulate matter into CO2, H2O and sludge; transform suspended and no Settleable solids; change nutrients as nitrogen and phosphorous; and degrades heavy metals. The microorganisms that remove organic matter in the processes are in generally facultative heterotrophic bacteria, forming heterogeneous populations. Is possible to find unicellular fungi, algae, protozoa and rotifers, that process the organic carbon source and oxygen, as well as the nitrogen and phosphorus because are vital for cell synthesis. The mixture of the substrate, in this case sludge leachate, molasses and wastewater is maintained ventilated by mechanical aeration diffusers. Considering as the biological processes work to remove dissolved material (< 45 microns), generating biomass, easily obtained by decantation processes. The design consists of an artificial support and aeration pumps, favoring develop microorganisms (denitrifying) using oxygen (O) with nitrate, resulting in nitrogen (N) in the gas phase. Thus, avoiding negative effects of the presence of ammonia or phosphorus. Overall the activated sludge system includes about 8 hours of hydraulic retention time, which does not prevent the demand for nitrification, which occurs on average in a value of MLSS 3,000 mg/L. The extended aeration works with times greater than 24 hours detention; with ratio of organic load/biomass inventory under 0.1; and average stay time (sludge age) more than 8 days. This project developed a pilot system with sludge leachate from Doña Juana landfill - RSDJ –, located in Bogota, Colombia, where they will be subjected to a process of activated sludge and extended aeration through a sequential Bach reactor - SBR, to be dump in hydric sources, avoiding ecological collapse. The system worked with a dwell time of 8 days, 30 L capacity, mainly by removing values of BOD and COD above 90%, with initial data of 1720 mg/L and 6500 mg/L respectively. Motivating the deliberate nitrification is expected to be possible commercial use diffused aeration systems for sludge leachate from landfills.

Keywords: sludge, landfill, leachate, SBR

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Authors: Kenneth A. Rostowsky, Alexander S. Maher, Nahian F. Chowdhury, Andrei Irimia

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The clinical significance of cerebral microbleeds (CMBs) due to mild traumatic brain injury (mTBI) remains unclear. Here we use magnetic resonance imaging (MRI), diffusion tensor imaging (DTI) and connectomic analysis to investigate the statistical association between mTBI-related CMBs, post-TBI changes to the human connectome and neurological/cognitive deficits. This study was undertaken in agreement with US federal law (45 CFR 46) and was approved by the Institutional Review Board (IRB) of the University of Southern California (USC). Two groups, one consisting of 26 (13 females) mTBI victims and another comprising 26 (13 females) healthy control (HC) volunteers were recruited through IRB-approved procedures. The acute Glasgow Coma Scale (GCS) score was available for each mTBI victim (mean µ = 13.2; standard deviation σ = 0.4). Each HC volunteer was assigned a GCS of 15 to indicate the absence of head trauma at the time of enrollment in our study. Volunteers in the HC and mTBI groups were matched according to their sex and age (HC: µ = 67.2 years, σ = 5.62 years; mTBI: µ = 66.8 years, σ = 5.93 years). MRI [including T1- and T2-weighted volumes, gradient recalled echo (GRE)/susceptibility weighted imaging (SWI)] and gradient echo (GE) DWI volumes were acquired using the same MRI scanner type (Trio TIM, Siemens Corp.). Skull-stripping and eddy current correction were implemented. DWI volumes were processed in TrackVis (http://trackvis.org) and 3D Slicer (http://www.slicer.org). Tensors were fit to DWI data to perform DTI, and tractography streamlines were then reconstructed using deterministic tractography. A voxel classifier was used to identify image features as CMB candidates using Microbleed Anatomic Rating Scale (MARS) guidelines. For each peri-lesional DTI streamline bundle, the null hypothesis was formulated as the statement that there was no neurological or cognitive deficit associated with between-scan differences in the mean FA of DTI streamlines within each bundle. The statistical significance of each hypothesis test was calculated at the α = 0.05 level, subject to the family-wise error rate (FWER) correction for multiple comparisons. Results: In HC volunteers, the along-track analysis failed to identify statistically significant differences in the mean FA of DTI streamline bundles. In the mTBI group, significant differences in the mean FA of peri-lesional streamline bundles were found in 21 out of 26 volunteers. In those volunteers where significant differences had been found, these differences were associated with an average of ~47% of all identified CMBs (σ = 21%). In 12 out of the 21 volunteers exhibiting significant FA changes, cognitive functions (memory acquisition and retrieval, top-down control of attention, planning, judgment, cognitive aspects of decision-making) were found to have deteriorated over the six months following injury (r = -0.32, p < 0.001). Our preliminary results suggest that acute post-TBI CMBs may be associated with cognitive decline in some mTBI patients. Future research should attempt to identify mTBI patients at high risk for cognitive sequelae.

Keywords: traumatic brain injury, magnetic resonance imaging, diffusion tensor imaging, connectomics

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Authors: Delphine Morales, Florian Lombart, Agathe Truchot, Pauline Maire, Pascale Vigneron, Antoine Galmiche, Catherine Lok, Muriel Vayssade

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Targeted therapy molecules are used as a first-line treatment for metastatic melanoma with B-Raf mutation. Nevertheless, these molecules can cause side effects to patients and are efficient on 50 to 60 % of them. Indeed, melanoma cell sensitivity to targeted therapy molecules is dependent on tumor microenvironment (cell-cell and cell-extracellular matrix interactions). To better unravel factors modulating cell sensitivity to B-Raf inhibitor, we have developed and compared several melanoma models: from metastatic melanoma cells cultured as monolayer (2D) to a co-culture in a 3D dermal equivalent. Cell response was studied in different melanoma cell lines such as SK-MEL-28 (mutant B-Raf (V600E), sensitive to Vemurafenib), SK-MEL-3 (mutant B-Raf (V600E), resistant to Vemurafenib) and a primary culture of dermal human fibroblasts (HDFn). Assays have initially been performed in a monolayer cell culture (2D), then a second time on a 3D dermal equivalent (dermal human fibroblasts embedded in a collagen gel). All cell lines were treated with Vemurafenib (a B-Raf inhibitor) for 48 hours at various concentrations. Cell sensitivity to treatment was assessed under various aspects: Cell proliferation (cell counting, EdU incorporation, MTS assay), MAPK signaling pathway analysis (Western-Blotting), Apoptosis (TUNEL), Cytokine release (IL-6, IL-1α, HGF, TGF-β, TNF-α) upon Vemurafenib treatment (ELISA) and histology for 3D models. In 2D configuration, the inhibitory effect of Vemurafenib on cell proliferation was confirmed on SK-MEL-28 cells (IC50=0.5 µM), and not on the SK-MEL-3 cell line. No apoptotic signal was detected in SK-MEL-28-treated cells, suggesting a cytostatic effect of the Vemurafenib rather than a cytotoxic one. The inhibition of SK-MEL-28 cell proliferation upon treatment was correlated with a strong expression decrease of phosphorylated proteins involved in the MAPK pathway (ERK, MEK, and AKT/PKB). Vemurafenib (from 5 µM to 10 µM) also slowed down HDFn proliferation, whatever cell culture configuration (monolayer or 3D dermal equivalent). SK-MEL-28 cells cultured in the dermal equivalent were still sensitive to high Vemurafenib concentrations. To better characterize all cell population impacts (melanoma cells, dermal fibroblasts) on Vemurafenib efficacy, cytokine release is being studied in 2D and 3D models. We have successfully developed and validated a relevant 3D model, mimicking cutaneous metastatic melanoma and tumor microenvironment. This 3D melanoma model will become more complex by adding a third cell population, keratinocytes, allowing us to characterize the epidermis influence on the melanoma cell sensitivity to Vemurafenib. In the long run, the establishment of more relevant 3D melanoma models with patients’ cells might be useful for personalized therapy development. The authors would like to thank the Picardie region and the European Regional Development Fund (ERDF) 2014/2020 for the funding of this work and Oise committee of "La ligue contre le cancer".

Keywords: 3D human skin model, melanoma, tissue engineering, vemurafenib efficiency

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