Search results for: priority order of basic features
Commenced in January 2007
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Paper Count: 19282

Search results for: priority order of basic features

82 Numerical Modeling of Phase Change Materials Walls under Reunion Island's Tropical Weather

Authors: Lionel Trovalet, Lisa Liu, Dimitri Bigot, Nadia Hammami, Jean-Pierre Habas, Bruno Malet-Damour

Abstract:

The MCP-iBAT1 project is carried out to study the behavior of Phase Change Materials (PCM) integrated in building envelopes in a tropical environment. Through the phase transitions (melting and freezing) of the material, thermal energy can be absorbed or released. This process enables the regulation of indoor temperatures and the improvement of thermal comfort for the occupants. Most of the commercially available PCMs are more suitable to temperate climates than to tropical climates. The case of Reunion Island is noteworthy as there are multiple micro-climates. This leads to our key question: developing one or multiple bio-based PCMs that cover the thermal needs of the different locations of the island. The present paper focuses on the numerical approach to select the PCM properties relevant to tropical areas. Numerical simulations have been carried out with two softwares: EnergyPlusTM and Isolab. The latter has been developed in the laboratory, with the implicit Finite Difference Method, in order to evaluate different physical models. Both are Thermal Dynamic Simulation (TDS) softwares that predict the building’s thermal behavior with one-dimensional heat transfers. The parameters used in this study are the construction’s characteristics (dimensions and materials) and the environment’s description (meteorological data and building surroundings). The building is modeled in accordance with the experimental setup. It is divided into two rooms, cells A and B, with same dimensions. Cell A is the reference, while in cell B, a layer of commercial PCM (Thermo Confort of MCI Technologies) has been applied to the inner surface of the North wall. Sensors are installed in each room to retrieve temperatures, heat flows, and humidity rates. The collected data are used for the comparison with the numerical results. Our strategy is to implement two similar buildings at different altitudes (Saint-Pierre: 70m and Le Tampon: 520m) to measure different temperature ranges. Therefore, we are able to collect data for various seasons during a condensed time period. The following methodology is used to validate the numerical models: calibration of the thermal and PCM models in EnergyPlusTM and Isolab based on experimental measures, then numerical testing with a sensitivity analysis of the parameters to reach the targeted indoor temperatures. The calibration relies on the past ten months’ measures (from September 2020 to June 2021), with a focus on one-week study on November (beginning of summer) when the effect of PCM on inner surface temperatures is more visible. A first simulation with the PCM model of EnergyPlus gave results approaching the measurements with a mean error of 5%. The studied property in this paper is the melting temperature of the PCM. By determining the representative temperature of winter, summer and inter-seasons with past annual’s weather data, it is possible to build a numerical model of multi-layered PCM. Hence, the combined properties of the materials will provide an optimal scenario for the application on PCM in tropical areas. Future works will focus on the development of bio-based PCMs with the selected properties followed by experimental and numerical validation of the materials. 1Materiaux ´ a Changement de Phase, une innovation pour le B ` ati Tropical

Keywords: energyplus, multi-layer of PCM, phase changing materials, tropical area

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81 Gene Expression Meta-Analysis of Potential Shared and Unique Pathways Between Autoimmune Diseases Under anti-TNFα Therapy

Authors: Charalabos Antonatos, Mariza Panoutsopoulou, Georgios K. Georgakilas, Evangelos Evangelou, Yiannis Vasilopoulos

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The extended tissue damage and severe clinical outcomes of autoimmune diseases, accompanied by the high annual costs to the overall health care system, highlight the need for an efficient therapy. Increasing knowledge over the pathophysiology of specific chronic inflammatory diseases, namely Psoriasis (PsO), Inflammatory Bowel Diseases (IBD) consisting of Crohn’s disease (CD) and Ulcerative colitis (UC), and Rheumatoid Arthritis (RA), has provided insights into the underlying mechanisms that lead to the maintenance of the inflammation, such as Tumor Necrosis Factor alpha (TNF-α). Hence, the anti-TNFα biological agents pose as an ideal therapeutic approach. Despite the efficacy of anti-TNFα agents, several clinical trials have shown that 20-40% of patients do not respond to treatment. Nowadays, high-throughput technologies have been recruited in order to elucidate the complex interactions in multifactorial phenotypes, with the most ubiquitous ones referring to transcriptome quantification analyses. In this context, a random effects meta-analysis of available gene expression cDNA microarray datasets was performed between responders and non-responders to anti-TNFα therapy in patients with IBD, PsO, and RA. Publicly available datasets were systematically searched from inception to 10th of November 2020 and selected for further analysis if they assessed the response to anti-TNFα therapy with clinical score indexes from inflamed biopsies. Specifically, 4 IBD (79 responders/72 non-responders), 3 PsO (40 responders/11 non-responders) and 2 RA (16 responders/6 non-responders) datasetswere selected. After the separate pre-processing of each dataset, 4 separate meta-analyses were conducted; three disease-specific and a single combined meta-analysis on the disease-specific results. The MetaVolcano R package (v.1.8.0) was utilized for a random-effects meta-analysis through theRestricted Maximum Likelihood (RELM) method. The top 1% of the most consistently perturbed genes in the included datasets was highlighted through the TopConfects approach while maintaining a 5% False Discovery Rate (FDR). Genes were considered as Differentialy Expressed (DEGs) as those with P ≤ 0.05, |log2(FC)| ≥ log2(1.25) and perturbed in at least 75% of the included datasets. Over-representation analysis was performed using Gene Ontology and Reactome Pathways for both up- and down-regulated genes in all 4 performed meta-analyses. Protein-Protein interaction networks were also incorporated in the subsequentanalyses with STRING v11.5 and Cytoscape v3.9. Disease-specific meta-analyses detected multiple distinct pro-inflammatory and immune-related down-regulated genes for each disease, such asNFKBIA, IL36, and IRAK1, respectively. Pathway analyses revealed unique and shared pathways between each disease, such as Neutrophil Degranulation and Signaling by Interleukins. The combined meta-analysis unveiled 436 DEGs, 86 out of which were up- and 350 down-regulated, confirming the aforementioned shared pathways and genes, as well as uncovering genes that participate in anti-inflammatory pathways, namely IL-10 signaling. The identification of key biological pathways and regulatory elements is imperative for the accurate prediction of the patient’s response to biological drugs. Meta-analysis of such gene expression data could aid the challenging approach to unravel the complex interactions implicated in the response to anti-TNFα therapy in patients with PsO, IBD, and RA, as well as distinguish gene clusters and pathways that are altered through this heterogeneous phenotype.

Keywords: anti-TNFα, autoimmune, meta-analysis, microarrays

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80 Extension of Moral Agency to Artificial Agents

Authors: Sofia Quaglia, Carmine Di Martino, Brendan Tierney

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Artificial Intelligence (A.I.) constitutes various aspects of modern life, from the Machine Learning algorithms predicting the stocks on Wall streets to the killing of belligerents and innocents alike on the battlefield. Moreover, the end goal is to create autonomous A.I.; this means that the presence of humans in the decision-making process will be absent. The question comes naturally: when an A.I. does something wrong when its behavior is harmful to the community and its actions go against the law, which is to be held responsible? This research’s subject matter in A.I. and Robot Ethics focuses mainly on Robot Rights and its ultimate objective is to answer the questions: (i) What is the function of rights? (ii) Who is a right holder, what is personhood and the requirements needed to be a moral agent (therefore, accountable for responsibility)? (iii) Can an A.I. be a moral agent? (ontological requirements) and finally (iv) if it ought to be one (ethical implications). With the direction to answer this question, this research project was done via a collaboration between the School of Computer Science in the Technical University of Dublin that oversaw the technical aspects of this work, as well as the Department of Philosophy in the University of Milan, who supervised the philosophical framework and argumentation of the project. Firstly, it was found that all rights are positive and based on consensus; they change with time based on circumstances. Their function is to protect the social fabric and avoid dangerous situations. The same goes for the requirements considered necessary to be a moral agent: those are not absolute; in fact, they are constantly redesigned. Hence, the next logical step was to identify what requirements are regarded as fundamental in real-world judicial systems, comparing them to that of ones used in philosophy. Autonomy, free will, intentionality, consciousness and responsibility were identified as the requirements to be considered a moral agent. The work went on to build a symmetrical system between personhood and A.I. to enable the emergence of the ontological differences between the two. Each requirement is introduced, explained in the most relevant theories of contemporary philosophy, and observed in its manifestation in A.I. Finally, after completing the philosophical and technical analysis, conclusions were drawn. As underlined in the research questions, there are two issues regarding the assignment of moral agency to artificial agent: the first being that all the ontological requirements must be present and secondly being present or not, whether an A.I. ought to be considered as an artificial moral agent. From an ontological point of view, it is very hard to prove that an A.I. could be autonomous, free, intentional, conscious, and responsible. The philosophical accounts are often very theoretical and inconclusive, making it difficult to fully detect these requirements on an experimental level of demonstration. However, from an ethical point of view it makes sense to consider some A.I. as artificial moral agents, hence responsible for their own actions. When considering artificial agents as responsible, there can be applied already existing norms in our judicial system such as removing them from society, and re-educating them, in order to re-introduced them to society. This is in line with how the highest profile correctional facilities ought to work. Noticeably, this is a provisional conclusion and research must continue further. Nevertheless, the strength of the presented argument lies in its immediate applicability to real world scenarios. To refer to the aforementioned incidents, involving the murderer of innocents, when this thesis is applied it is possible to hold an A.I. accountable and responsible for its actions. This infers removing it from society by virtue of its un-usability, re-programming it and, only when properly functioning, re-introducing it successfully

Keywords: artificial agency, correctional system, ethics, natural agency, responsibility

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79 Magnesium Nanoparticles for Photothermal Therapy

Authors: E. Locatelli, I. Monaco, R. C. Martin, Y. Li, R. Pini, M. Chiariello, M. Comes Franchini

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Despite the many advantages of application of nanomaterials in the field of nanomedicine, increasing concerns have been expressed on their potential adverse effects on human health. There is urgency for novel green strategies toward novel materials with enhanced biocompatibility using safe reagents. Photothermal ablation therapy, which exploits localized heat increase of a few degrees to kill cancer cells, has appeared recently as a non-invasive and highly efficient therapy against various cancer types; anyway new agents able to generate hyperthermia when irradiated are needed and must have precise biocompatibility in order to avoid damage to healthy tissues and prevent toxicity. Recently, there has been increasing interest in magnesium as a biomaterial: it is the fourth most abundant cation in the human body, and it is essential for human metabolism. However magnesium nanoparticles (Mg NPs) have had limited diffusion due to the high reduction potential of magnesium cations, which makes NPs synthesis challenging. Herein, we report the synthesis of Mg NPs and their surface functionalization for the obtainment of a stable and biocompatible nanomaterial suitable for photothermal ablation therapy against cancer. We synthesized the Mg crystals by reducing MgCl2 with metallic lithium and exploiting naphthalene as an electron carrier: the lithium–naphthalene complex acts as the real reducing agent. Firstly, the nanocrystal particles were coated with the ligand 12-ethoxy ester dodecanehydroxamic acid, and then entrapped into water-dispersible polymeric micelles (PMs) made of the FDA-approved PLGA-b-PEG-COOH copolymer using the oil-in-water emulsion technique. Lately, we developed a more straightforward methodology by introducing chitosan, a highly biocompatible natural product, at the beginning of the process, simultaneously using lithium–naphthalene complex, thus having a one-pot procedure for the formation and surface modification of MgNPs. The obtained MgNPs were purified and fully characterized, showing diameters in the range of 50-300 nm. Notably, when coated with chitosan the particles remained stable as dry powder for more than 10 months. We proved the possibility of generating a temperature rise of a few to several degrees once MgNPs were illuminated using a 810 nm diode laser operating in continuous wave mode: the temperature rise resulted significant (0-15 °C) and concentration dependent. We then investigated potential cytotoxicity of the MgNPs: we used HN13 epithelial cells, derived from a head and neck squamous cell carcinoma and the hepa1-6 cell line, derived from hepatocellular carcinoma and very low toxicity was observed for both nanosystems. Finally, in vivo photothermal therapy was performed on xenograft hepa1-6 tumor bearing mice: the animals were treated with MgNPs coated with chitosan and showed no sign of suffering after the injection. After 12 hours the tumor was exposed to near-infrared laser light. The results clearly showed an extensive damage to tumor tissue after only 2 minutes of laser irradiation at 3Wcm-1, while no damage was reported when the tumor was treated with the laser and saline alone in control group. Despite the lower photothermal efficiency of Mg with respect to Au NPs, we consider MgNPs a promising, safe and green candidate for future clinical translations.

Keywords: chitosan, magnesium nanoparticles, nanomedicine, photothermal therapy

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78 Quality in Healthcare: An Autism-Friendly Hospital Emergency Waiting Room

Authors: Elena Bellini, Daniele Mugnaini, Michele Boschetto

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People with an Autistic Spectrum Disorder and an Intellectual Disability who need to attend a Hospital Emergency Waiting Room frequently present high levels of discomfort and challenging behaviors due to stress-related hyperarousal, sensory sensitivity, novelty-anxiety, communication and self-regulation difficulties. Increased agitation and acting out also disturb the diagnostic and therapeutic processes, and the emergency room climate. Architectural design disciplines aimed at reducing distress in hospitals or creating autism-friendly environments are called for to find effective answers to this particular need. A growing number of researchers are considering the physical environment as an important point of intervention for people with autism. It has been shown that providing the right setting can help enhance confidence and self-esteem and can have a profound impact on their health and wellbeing. Environmental psychology has evaluated the perceived quality of care, looking at the design of hospital rooms, paths and circulation, waiting rooms, services and devices. Furthermore, many studies have investigated the influence of the hospital environment on patients, in terms of stress-reduction and therapeutic intervention’ speed, but also on health professionals and their work. Several services around the world are organizing autism-friendly hospital environments which involve the architecture and the specific staff training. In Italy, the association Spes contra spem has promoted and published, in 2013, the ‘Chart of disabled people in the hospital’. It stipulates that disabled people should have equal rights to accessible and high-quality care. There are a few Italian examples of therapeutic programmes for autistic people as the Dama project in Milan and the recent experience of Children and Autism Foundation in Pordenone. Careggi’s Emergency Waiting Room in Florence has been built to satisfy this challenge. This project of research comes from a collaboration between the technical staff of Careggi Hospital, the Center for autism PAMAPI and some architects expert in the sensory environment. The methodology of focus group involved architects, psychologists and professionals through a transdisciplinary research, centered on the links between the spatial characteristics and clinical state of people with ASD. The relationship between architectural space and quality of life is studied to pay maximum attention to users’ needs and to support the medical staff in their work by a specific program of training. The result of this research is a sum of criteria used to design the emergency waiting room, that will be illustrated. A protected room, with a clear space design, maximizes comprehension and predictability. The multisensory environment is thought to help sensory integration and relaxation. Visual communication through Ipad allows an anticipated understanding of medical procedures, and a specific technological system supports requests, choices and self-determination in order to fit sensory stimulation to personal preferences, especially for hypo and hypersensitive people. All these characteristics should ensure a better regulation of the arousal, less behavior problems, improving treatment accessibility, safety, and effectiveness. First results about patient-satisfaction levels will be presented.

Keywords: accessibility of care, autism-friendly architecture, personalized therapeutic process, sensory environment

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77 Distributed Listening in Intensive Care: Nurses’ Collective Alarm Responses Unravelled through Auditory Spatiotemporal Trajectories

Authors: Michael Sonne Kristensen, Frank Loesche, James Foster, Elif Ozcan, Judy Edworthy

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Auditory alarms play an integral role in intensive care nurses’ daily work. Most medical devices in the intensive care unit (ICU) are designed to produce alarm sounds in order to make nurses aware of immediate or prospective safety risks. The utilisation of sound as a carrier of crucial patient information is highly dependent on nurses’ presence - both physically and mentally. For ICU nurses, especially the ones who work with stationary alarm devices at the patient bed space, it is a challenge to display ‘appropriate’ alarm responses at all times as they have to navigate with great flexibility in a complex work environment. While being primarily responsible for a small number of allocated patients they are often required to engage with other nurses’ patients, relatives, and colleagues at different locations inside and outside the unit. This work explores the social strategies used by a team of nurses to comprehend and react to the information conveyed by the alarms in the ICU. Two main research questions guide the study: To what extent do alarms from a patient bed space reach the relevant responsible nurse by direct auditory exposure? By which means do responsible nurses get informed about their patients’ alarms when not directly exposed to the alarms? A comprehensive video-ethnographic field study was carried out to capture and evaluate alarm-related events in an ICU. The study involved close collaboration with four nurses who wore eye-level cameras and ear-level binaural audio recorders during several work shifts. At all time the entire unit was monitored by multiple video and audio recorders. From a data set of hundreds of hours of recorded material information about the nurses’ location, social interaction, and alarm exposure at any point in time was coded in a multi-channel replay-interface. The data shows that responsible nurses’ direct exposure and awareness of the alarms of their allocated patients vary significantly depending on work load, social relationships, and the location of the patient’s bed space. Distributed listening is deliberately employed by the nursing team as a social strategy to respond adequately to alarms, but the patterns of information flow prompted by alarm-related events are not uniform. Auditory Spatiotemporal Trajectory (AST) is proposed as a methodological label to designate the integration of temporal, spatial and auditory load information. As a mixed-method metrics it provides tangible evidence of how nurses’ individual alarm-related experiences differ from one another and from stationary points in the ICU. Furthermore, it is used to demonstrate how alarm-related information reaches the individual nurse through principles of social and distributed cognition, and how that information relates to the actual alarm event. Thereby it bridges a long-standing gap in the literature on medical alarm utilisation between, on the one hand, initiatives to measure objective data of the medical sound environment without consideration for any human experience, and, on the other hand, initiatives to study subjective experiences of the medical sound environment without detailed evidence of the objective characteristics of the environment.

Keywords: auditory spatiotemporal trajectory, medical alarms, social cognition, video-ethography

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76 Exploring the Dose-Response Association of Lifestyle Behaviors and Mental Health among High School Students in the US: A Secondary Analysis of 2021 Adolescent Behaviors and Experiences Survey Data

Authors: Layla Haidar, Shari Esquenazi-Karonika

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Introduction: Mental health includes one’s emotional, psychological, and interpersonal well-being; it ranges from “good” to “poor” on a continuum. At the individual-level, it affects how a person thinks, feels, and acts. Moreover, it determines how they cope with stress, relate to others, and interface with their surroundings. Research has yielded that mental health is directly related with short- and long-term physical health (including chronic disease), health risk behaviors, education-level, employment, and social relationships. As is the case with physical conditions like diabetes, heart disease, and cancer, mitigating the behavioral and genetic risks of debilitating mental health conditions like anxiety and depression can nurture a healthier quality of mental health throughout one’s life. In order to maximize the benefits of prevention, it is important to identify modifiable risks and develop protective habits earlier in life. Methods: The Adolescent Behaviors and Experiences Survey (ABES) dataset was used for this study. The ABES survey was administered to high school students (9th-12th grade) during January 2021- June 2021 by the Centers for Disease Control and Prevention (CDC). The data was analyzed to identify any associations between feelings of sadness, hopelessness, or increased suicidality among high school students with relation to their participation on one or more sports teams and their average daily consumed screen time. Data was analyzed using descriptive and multivariable analytic techniques. A multinomial logistic regression of each variable was conducted to examine if there was an association, while controlling for grade-level, sex, and race. Results: The findings from this study are insightful for administrators and policymakers who wish to address mounting concerns related to student mental health. The study revealed that compared to a student who participated on zero sports teams, students who participated in 1 or more sports teams showed a significantly increased risk of depression (p<0.05). Conversely, the rate of depression in students was significantly less in those who consumed 5 or more hours of screen time per day, compared to those who consumed less than 1 hour per day of screen time (p<0.05). Conclusion: These findings are informative and highlight the importance of understanding the nuances of student participation on sports teams (e.g., physical exertion, social dynamics of team, and the level of competitiveness within the sport). Likewise, the context of an individual’s screen time (e.g., social media, engaging in team-based video games, or watching television) can inform parental or school-based policies about screen time activity. Although physical activity has been proven to be important for emotional and physical well-being of youth, playing on multiple teams could have negative consequences on the emotional state of high school students potentially due to fatigue, overtraining, and injuries. Existing literature has highlighted the negative effects of screen time; however, further research needs to consider the type of screen-based consumption to better understand its effects on mental health.

Keywords: behavioral science, mental health, adolescents, prevention

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75 Numerical Analysis of Mandible Fracture Stabilization System

Authors: Piotr Wadolowski, Grzegorz Krzesinski, Piotr Gutowski

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The aim of the presented work is to recognize the impact of mini-plate application approach on the stress and displacement within the stabilization devices and surrounding bones. The mini-plate osteosynthesis technique is widely used by craniofacial surgeons as an improved replacement of wire connection approach. Many different types of metal plates and screws are used to the physical connection of fractured bones. Below investigation is based on a clinical observation of patient hospitalized with mini-plate stabilization system. Analysis was conducted on a solid mandible geometry, which was modeled basis on the computed tomography scan of the hospitalized patient. In order to achieve most realistic connected system behavior, the cortical and cancellous bone layers were assumed. The temporomandibular joint was simplified to the elastic element to allow physiological movement of loaded bone. The muscles of mastication system were reduced to three pairs, modeled as shell structures. Finite element grid was created by the ANSYS software, where hexahedral and tetrahedral variants of SOLID185 element were used. A set of nonlinear contact conditions were applied on connecting devices and bone common surfaces. Properties of particular contact pair depend on screw - mini-plate connection type and possible gaps between fractured bone around osteosynthesis region. Some of the investigated cases contain prestress introduced to the mini-plate during the application, what responds the initial bending of the connecting device to fit the retromolar fossa region. Assumed bone fracture occurs within the mandible angle zone. Due to the significant deformation of the connecting plate in some of the assembly cases the elastic-plastic model of titanium alloy was assumed. The bone tissues were covered by the orthotropic material. As a loading were used the gauge force of magnitude of 100N applied in three different locations. Conducted analysis shows significant impact of mini-plate application methodology on the stress distribution within the miniplate. Prestress effect introduces additional loading, which leads to locally exceed the titanium alloy yield limit. Stress in surrounding bone increases rapidly around the screws application region, exceeding assumed bone yield limit, what indicate the local bone destruction. Approach with the doubled mini-plate shows increased stress within the connector due to the too rigid connection, where the main path of loading leads through the mini-plates instead of plates and connected bones. Clinical observations confirm more frequent plate destruction of stiffer connections. Some of them could be an effect of decreased low cyclic fatigue capability caused by the overloading. The executed analysis prove that the mini-plate system provides sufficient support to mandible fracture treatment, however, many applicable solutions shifts the entire system to the allowable material limits. The results show that connector application with the initial loading needs to be carefully established due to the small material capability tolerances. Comparison to the clinical observations allows optimizing entire connection to prevent future incidents.

Keywords: mandible fracture, mini-plate connection, numerical analysis, osteosynthesis

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74 Membrane Permeability of Middle Molecules: A Computational Chemistry Approach

Authors: Sundaram Arulmozhiraja, Kanade Shimizu, Yuta Yamamoto, Satoshi Ichikawa, Maenaka Katsumi, Hiroaki Tokiwa

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Drug discovery is shifting from small molecule based drugs targeting local active site to middle molecules (MM) targeting large, flat, and groove-shaped binding sites, for example, protein-protein interface because at least half of all targets assumed to be involved in human disease have been classified as “difficult to drug” with traditional small molecules. Hence, MMs such as peptides, natural products, glycans, nucleic acids with various high potent bioactivities become important targets for drug discovery programs in the recent years as they could be used for ‘undruggable” intracellular targets. Cell membrane permeability is one of the key properties of pharmacodynamically active MM drug compounds and so evaluating this property for the potential MMs is crucial. Computational prediction for cell membrane permeability of molecules is very challenging; however, recent advancement in the molecular dynamics simulations help to solve this issue partially. It is expected that MMs with high membrane permeability will enable drug discovery research to expand its borders towards intracellular targets. Further to understand the chemistry behind the permeability of MMs, it is necessary to investigate their conformational changes during the permeation through membrane and for that their interactions with the membrane field should be studied reliably because these interactions involve various non-bonding interactions such as hydrogen bonding, -stacking, charge-transfer, polarization dispersion, and non-classical weak hydrogen bonding. Therefore, parameters-based classical mechanics calculations are hardly sufficient to investigate these interactions rather, quantum mechanical (QM) calculations are essential. Fragment molecular orbital (FMO) method could be used for such purpose as it performs ab initio QM calculations by dividing the system into fragments. The present work is aimed to study the cell permeability of middle molecules using molecular dynamics simulations and FMO-QM calculations. For this purpose, a natural compound syringolin and its analogues were considered in this study. Molecular simulations were performed using NAMD and Gromacs programs with CHARMM force field. FMO calculations were performed using the PAICS program at the correlated Resolution-of-Identity second-order Moller Plesset (RI-MP2) level with the cc-pVDZ basis set. The simulations clearly show that while syringolin could not permeate the membrane, its selected analogues go through the medium in nano second scale. These correlates well with the existing experimental evidences that these syringolin analogues are membrane-permeable compounds. Further analyses indicate that intramolecular -stacking interactions in the syringolin analogues influenced their permeability positively. These intramolecular interactions reduce the polarity of these analogues so that they could permeate the lipophilic cell membrane. Conclusively, the cell membrane permeability of various middle molecules with potent bioactivities is efficiently studied using molecular dynamics simulations. Insight of this behavior is thoroughly investigated using FMO-QM calculations. Results obtained in the present study indicate that non-bonding intramolecular interactions such as hydrogen-bonding and -stacking along with the conformational flexibility of MMs are essential for amicable membrane permeation. These results are interesting and are nice example for this theoretical calculation approach that could be used to study the permeability of other middle molecules. This work was supported by Japan Agency for Medical Research and Development (AMED) under Grant Number 18ae0101047.

Keywords: fragment molecular orbital theory, membrane permeability, middle molecules, molecular dynamics simulation

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73 Re-Designing Community Foodscapes to Enhance Social Inclusion in Sustainable Urban Environments

Authors: Carles Martinez-Almoyna Gual, Jiwon Choi

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Urban communities face risks of disintegration and segregation as a consequence of globalised migration processes towards urban environments. Linking social and cultural components with environmental and economic dimensions becomes the goal of all the disciplines that aim to shape more sustainable urban environments. Solutions require interdisciplinary approaches and the use of a complex array of tools. One of these tools is the implementation of urban farming, which provides a wide range of advantages for creating more inclusive spaces and integrated communities. Since food is strongly related to the values and identities of any cultural group, it can be used as a medium to promote social inclusion in the context of urban multicultural societies. By bringing people together into specific urban sites, food production can be integrated into multifunctional spaces while addressing social, economic and ecological goals. The goal of this research is to assess different approaches to urban agriculture by analysing three existing community gardens located in Newtown, a suburb of Wellington, New Zealand. As a context for developing research, Newtown offers different approaches to urban farming and is really valuable for observing current trends of socialization in diverse and multicultural societies. All three spaces are located on public land owned by Wellington City Council and confined to a small, complex and progressively denser urban area. The developed analysis was focused on social, cultural and physical dimensions, combining community engagement with different techniques of spatial assessment. At the same time, a detailed investigation of each community garden was conducted with comparative analysis methodologies. This multidirectional setting of the analysis was established for extracting from the case studies both specific and typological knowledge. Each site was analysed and categorised under three broad themes: people, space and food. The analysis revealed that all three case studies had really different spatial settings, different approaches to food production and varying profiles of supportive communities. The main differences identified were demographics, values, objectives, internal organization, appropriation, and perception of the space. The community gardens were approached as case studies for developing design research. Following participatory design processes with the different communities, the knowledge gained from the analysis was used for proposing changes in the physical environment. The end goal of the design research was to improve the capacity of the spaces to facilitate social inclusiveness. In order to generate tangible changes, a range of small, strategic and feasible spatial interventions was explored. The smallness of the proposed interventions facilitates implementation by reducing time frames, technical resources, funding needs, and legal processes, working within the community´s own realm. These small interventions are expected to be implemented over time as part of an ongoing collaboration between the different communities, the university, and the local council. The applied research methodology showcases the capacity of universities to develop civic engagement by working with real communities that have concrete needs and face overall threats of disintegration and segregation.

Keywords: community gardening, landscape architecture, participatory design, placemaking, social inclusion

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72 How the Writer Tells the Story Should Be the Primary Concern rather than Who Can Write about Whom: The Limits of Cultural Appropriation Vis-à-Vis The Ethics of Narrative Empathy

Authors: Alexandra Cheira

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Cultural appropriation has been theorised as a form of colonialism in which members of a dominant culture reduce cultural elements that are deeply meaningful to a minority culture to the category of the “exotic other” since they do not experience the oppression and discriminations faced by members of the minority culture. Yet, in the particular case of literature, writers such as Lionel Shriver and Bernardine Evaristo have argued that authors from a cultural majority have a right to write in the voice of someone from a cultural minority, hence attacking the idea that this is a form of cultural appropriation. By definition, Shriver and Evaristo claim, writers are supposed to write beyond their own culture, gender, class, and/ or race. In this light, this paper discusses the limits of cultural appropriation vis-à-vis the ethics of narrative empathy by addressing the mixed critical reception of Kathryn Stockett’s The Help (2009) and Jeanine Cummins’s American Dirt (2020). In fact, both novels were acclaimed as global eye-openers regarding the struggles of respectively South American migrants and African American maids. At the same time, both novelists have been accused of cultural appropriation by telling a story that is not theirs to tell, given the fact that they are white women telling these stories in what critics have argued is really an American voice telling a story to American readers.These claims will be investigated within the framework of Edward Said’s foundational examination of Orientalism in the field of postcolonial studies as a Western style for authoritatively restructuring the Orient. This means that Orientalist stereotypes regarding Eastern cultures have implicitly validated colonial and imperial pursuits, in the specific context of literary representations of African American and Mexican cultures by white writers. At the same time, the conflicted reception of American Dirt and The Help will be examined within the critical framework of narrative empathy as theorised by Suzanne Keen. Hence, there will be a particular focus on the way a reader’s heated perception that the author’s perspective is purely dishonest can result from a friction between an author’s intention and a reader’s experience of narrative empathy, while a shared sense of empathy between authors and readers can be a rousing momentum to move beyond literary response to social action.Finally, in order to assess that “the key question should not be who can write about whom, but how the writer tells the story”, the recent controversy surrounding Dutch author Marieke Lucas Rijneveld’s decision to resign the translation of American poet Amanda Gorman’s work into Dutch will be duly investigated. In fact, Rijneveld stepped out after journalist and activist Janice Deul criticised Dutch publisher Meulenhoff for choosing a translator who was not also Black, despite the fact that 22-year-old Gorman had selected the 29-year-old Rijneveld herself, as a fellow young writer who had likewise come to fame early on in life. In this light, the critical argument that the controversial reception of The Help reveals as much about US race relations in the early twenty-first century as about the complex literary transactions between individual readers and the novel itself will also be discussed in the extended context of American Dirt and white author Marieke Rijneveld’s withdrawal from the projected translation of Black poet Amanda Gorman.

Keywords: cultural appropriation, cultural stereotypes, narrative empathy, race relations

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71 Comprehensive Literature Review of the Humanistic Burden of Clostridium (Clostridiodes) difficile Infection

Authors: Caroline Seo, Jennifer Stephens, Kirstin H. Heinrich

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Background: Clostridiodes (formerly Clostridium) difficile infection (CDI) is an anaerobic, spore-forming bacterium with manifestations including diarrhea, pseudomembranous colitis and toxic megacolon. Despite general understanding that CDI may be associated with marked burden on patients’ health, there has been limited information available on the humanistic burden of CDI. The objective of this literature review was to summarize the published data on the humanistic burden of CDI globally, in order to better inform future research efforts and increase awareness of the patient perspective in this disease. Methods: A comprehensive literature review of the past 15 years (2002-2017) was conducted using MEDLINE, Embase and Cumulative Index of Nursing and Allied Health Literature. Additional searches were conducted from conference proceedings (2015-2017). Articles selected were studies specifically designed to examine the humanistic burden of illness associated with adult patients with CDI. Results: Of 3,325 articles or abstracts identified, 33 remained after screening and full text review. Sixty percent (60%) were published in 2016 or 2017. Data from the United States or Western Europe were most common. Data from Brazil, Canada, China and Spain also exist. Thirteen (13) studies used validated patient-reported outcomes instruments, mostly EQ-5D utility and SF-36 generic instruments. Three (3) studies used CDI-specific instruments (CDiff32, CDI-DaySyms). The burden of CDI impacts patients in multiple health-related quality of life (HRQOL) domains. SF-36 domains with the largest decrements compared to other GI diarrheal diseases (IBS-D and Crohn’s) were role physical, physical functioning, vitality, social functioning, and role emotional. Reported EQ-5D utilities for CDI ranged from 0.35-0.42 compared to 0.65 in Crohn’s and 0.72 in IBS-D. The majority of papers addressed physical functioning and mental health domains (67% for both). Across various studies patients reported weakness, lack of appetite, sleep disturbance, functional dependence, and decreased activities of daily lives due to the continuous diarrhea. Due to lack of control over this infection, CDI also impacts the psychological and emotional quality of life of the patients. Patients reported feelings of fear, anxiety, frustration, depression, and embarrassment. Additionally, the type of disease (primary vs. recurrent) may impact mental health. One study indicated that there is a decrement in SF-36 mental scores in patients with recurrent CDI, in comparison to patients with primary CDI. Other domains highlighted by these studies include pain (27%), social isolation (27%), vitality and fatigue (24%), self-care (9%), and caregiver burden (0%). Two studies addressed work productivity, with 1 of these studies reporting that CDI patients had the highest work productivity and activity impairment scores among the gastrointestinal diseases. No study specifically included caregiver self-report. However, 3 studies did provide mention of patients’ worry on how their diagnosis of CDI would impact family, caregivers, and/or friends. Conclusions: Despite being a serious public health issue there has been a paucity of research on the HRQOL among those with CDI. While progress is being made, gaps exist in understanding the burden on patients, caregivers, and families. Future research is warranted to aid understanding of the CDI patient perspective.

Keywords: burden, Clostridiodes, difficile, humanistic, infection

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70 EGF Serum Level in Diagnosis and Prediction of Mood Disorder in Adolescents and Young Adults

Authors: Monika Dmitrzak-Weglarz, Aleksandra Rajewska-Rager, Maria Skibinska, Natalia Lepczynska, Piotr Sibilski, Joanna Pawlak, Pawel Kapelski, Joanna Hauser

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Epidermal growth factor (EGF) is a well-known neurotrophic factor that involves in neuronal growth and synaptic plasticity. The proteomic research provided in order to identify novel candidate biological markers for mood disorders focused on elevated EGF serum level in patients during depression episode. However, the EGF association with mood disorder spectrum among adolescents and young adults has not been studied extensively. In this study, we aim to investigate the serum levels of EGF in adolescents and young adults during hypo/manic, depressive episodes and in remission compared to healthy control group. In our study, we involved 80 patients aged 12-24 years in 2-year follow-up study with a primary diagnosis of mood disorder spectrum, and 35 healthy volunteers matched by age and gender. Diagnoses were established according to DSM-IV-TR criteria using structured clinical interviews: K-SADS for child and adolescents, and SCID for young adults. Clinical and biological evaluations were made at baseline and euthymic mood (at 3th or 6th month of treatment and after 1 and 2 years). The Young Mania Rating Scale and Hamilton Rating Scale for Depression were used for assessment. The study protocols were approved by the relevant ethics committee. Serum protein concentration was determined by Enzyme-Linked Immunosorbent Assays (ELISA) method. Human EGF (cat. no DY 236) DuoSet ELISA kit was used (R&D Systems). Serum EGF levels were analysed with following variables: age, age under 18 and above 18 years old, sex, family history of affective disorders, drug-free vs. medicated. Shapiro-Wilk test was used to test the normality of the data. The homogeneity of variance was calculated with Levene’s test. EGF levels showed non-normal distribution and the homogeneity of variance was violated. Non-parametric tests: Mann-Whitney U test, Kruskall-Wallis ANOVA, Friedman’s ANOVA, Wilcoxon signed rank test, Spearman correlation coefficient was applied in the analyses The statistical significance level was set at p<0.05. Elevated EGF level at baseline (p=0.001) and at month 24 (p=0.02) was detected in study subjects compared with controls. Increased EGF level in women at month 12 (p=0.02) compared to men in study group have been observed. Using Wilcoxon signed rank test differences in EGF levels were detected: decrease from baseline to month 3 (p=0.014) and increase comparing: month 3 vs. 24 (p=0.013); month 6 vs. 12 (p=0.021) and vs. 24 (p=0.008). EGF level at baseline was negatively correlated with depression and mania occurrence at 24 months. EGF level at 24 months was positively correlated with depression and mania occurrence at 12 months. No other correlations of EGF levels with clinical and demographical variables have been detected. The findings of the present study indicate that EGF serum level is significantly elevated in the study group of patients compared to the controls. We also observed fluctuations in EGF levels during two years of disease observation. EGF seems to be useful as an early marker for prediction of diagnosis, course of illness and treatment response in young patients during first episode od mood disorders, which requires further investigation. Grant was founded by National Science Center in Poland no 2011/03/D/NZ5/06146.

Keywords: biological marker, epidermal growth factor, mood disorders, prediction

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69 Colloid-Based Biodetection at Aqueous Electrical Interfaces Using Fluidic Dielectrophoresis

Authors: Francesca Crivellari, Nicholas Mavrogiannis, Zachary Gagnon

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Portable diagnostic methods have become increasingly important for a number of different purposes: point-of-care screening in developing nations, environmental contamination studies, bio/chemical warfare agent detection, and end-user use for commercial health monitoring. The cheapest and most portable methods currently available are paper-based – lateral flow and dipstick methods are widely available in drug stores for use in pregnancy detection and blood glucose monitoring. These tests are successful because they are cheap to produce, easy to use, and require minimally invasive sampling. While adequate for their intended uses, in the realm of blood-borne pathogens and numerous cancers, these paper-based methods become unreliable, as they lack the nM/pM sensitivity currently achieved by clinical diagnostic methods. Clinical diagnostics, however, utilize techniques involving surface plasmon resonance (SPR) and enzyme-linked immunosorbent assays (ELISAs), which are expensive and unfeasible in terms of portability. To develop a better, competitive biosensor, we must reduce the cost of one, or increase the sensitivity of the other. Electric fields are commonly utilized in microfluidic devices to manipulate particles, biomolecules, and cells. Applications in this area, however, are primarily limited to interfaces formed between immiscible interfaces. Miscible, liquid-liquid interfaces are common in microfluidic devices, and are easily reproduced with simple geometries. Here, we demonstrate the use of electrical fields at liquid-liquid electrical interfaces, known as fluidic dielectrophoresis, (fDEP) for biodetection in a microfluidic device. In this work, we apply an AC electric field across concurrent laminar streams with differing conductivities and permittivities to polarize the interface and induce a discernible, near-immediate, frequency-dependent interfacial tilt. We design this aqueous electrical interface, which becomes the biosensing “substrate,” to be intelligent – it “moves” only when a target of interest is present. This motion requires neither labels nor expensive electrical equipment, so the biosensor is inexpensive and portable, yet still capable of sensitive detection. Nanoparticles, due to their high surface-area-to-volume ratio, are often incorporated to enhance detection capabilities of schemes like SPR and fluorimetric assays. Most studies currently investigate binding at an immobilized solid-liquid or solid-gas interface, where particles are adsorbed onto a planar surface, functionalized with a receptor to create a reactive substrate, and subsequently flushed with a fluid or gas with the relevant analyte. These typically involve many preparation and rinsing steps, and are susceptible to surface fouling. Our microfluidic device is continuously flowing and renewing the “substrate,” and is thus not subject to fouling. In this work, we demonstrate the ability to electrokinetically detect biomolecules binding to functionalized nanoparticles at liquid-liquid interfaces using fDEP. In biotin-streptavidin experiments, we report binding detection limits on the order of 1-10 pM, without amplifying signals or concentrating samples. We also demonstrate the ability to detect this interfacial motion, and thus the presence of binding, using impedance spectroscopy, allowing this scheme to become non-optical, in addition to being label-free.

Keywords: biodetection, dielectrophoresis, microfluidics, nanoparticles

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68 Fuzzy Multi-Objective Approach for Emergency Location Transportation Problem

Authors: Bidzina Matsaberidze, Anna Sikharulidze, Gia Sirbiladze, Bezhan Ghvaberidze

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In the modern world emergency management decision support systems are actively used by state organizations, which are interested in extreme and abnormal processes and provide optimal and safe management of supply needed for the civil and military facilities in geographical areas, affected by disasters, earthquakes, fires and other accidents, weapons of mass destruction, terrorist attacks, etc. Obviously, these kinds of extreme events cause significant losses and damages to the infrastructure. In such cases, usage of intelligent support technologies is very important for quick and optimal location-transportation of emergency service in order to avoid new losses caused by these events. Timely servicing from emergency service centers to the affected disaster regions (response phase) is a key task of the emergency management system. Scientific research of this field takes the important place in decision-making problems. Our goal was to create an expert knowledge-based intelligent support system, which will serve as an assistant tool to provide optimal solutions for the above-mentioned problem. The inputs to the mathematical model of the system are objective data, as well as expert evaluations. The outputs of the system are solutions for Fuzzy Multi-Objective Emergency Location-Transportation Problem (FMOELTP) for disasters’ regions. The development and testing of the Intelligent Support System were done on the example of an experimental disaster region (for some geographical zone of Georgia) which was generated using a simulation modeling. Four objectives are considered in our model. The first objective is to minimize an expectation of total transportation duration of needed products. The second objective is to minimize the total selection unreliability index of opened humanitarian aid distribution centers (HADCs). The third objective minimizes the number of agents needed to operate the opened HADCs. The fourth objective minimizes the non-covered demand for all demand points. Possibility chance constraints and objective constraints were constructed based on objective-subjective data. The FMOELTP was constructed in a static and fuzzy environment since the decisions to be made are taken immediately after the disaster (during few hours) with the information available at that moment. It is assumed that the requests for products are estimated by homeland security organizations, or their experts, based upon their experience and their evaluation of the disaster’s seriousness. Estimated transportation times are considered to take into account routing access difficulty of the region and the infrastructure conditions. We propose an epsilon-constraint method for finding the exact solutions for the problem. It is proved that this approach generates the exact Pareto front of the multi-objective location-transportation problem addressed. Sometimes for large dimensions of the problem, the exact method requires long computing times. Thus, we propose an approximate method that imposes a number of stopping criteria on the exact method. For large dimensions of the FMOELTP the Estimation of Distribution Algorithm’s (EDA) approach is developed.

Keywords: epsilon-constraint method, estimation of distribution algorithm, fuzzy multi-objective combinatorial programming problem, fuzzy multi-objective emergency location/transportation problem

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67 Integrated Mathematical Modeling and Advance Visualization of Magnetic Nanoparticle for Drug Delivery, Drug Release and Effects to Cancer Cell Treatment

Authors: Norma Binti Alias, Che Rahim Che The, Norfarizan Mohd Said, Sakinah Abdul Hanan, Akhtar Ali

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This paper discusses on the transportation of magnetic drug targeting through blood within vessels, tissues and cells. There are three integrated mathematical models to be discussed and analyze the concentration of drug and blood flow through magnetic nanoparticles. The cell therapy brought advancement in the field of nanotechnology to fight against the tumors. The systematic therapeutic effect of Single Cells can reduce the growth of cancer tissue. The process of this nanoscale phenomena system is able to measure and to model, by identifying some parameters and applying fundamental principles of mathematical modeling and simulation. The mathematical modeling of single cell growth depends on three types of cell densities such as proliferative, quiescent and necrotic cells. The aim of this paper is to enhance the simulation of three types of models. The first model represents the transport of drugs by coupled partial differential equations (PDEs) with 3D parabolic type in a cylindrical coordinate system. This model is integrated by Non-Newtonian flow equations, leading to blood liquid flow as the medium for transportation system and the magnetic force on the magnetic nanoparticles. The interaction between the magnetic force on drug with magnetic properties produces induced currents and the applied magnetic field yields forces with tend to move slowly the movement of blood and bring the drug to the cancer cells. The devices of nanoscale allow the drug to discharge the blood vessels and even spread out through the tissue and access to the cancer cells. The second model is the transport of drug nanoparticles from the vascular system to a single cell. The treatment of the vascular system encounters some parameter identification such as magnetic nanoparticle targeted delivery, blood flow, momentum transport, density and viscosity for drug and blood medium, intensity of magnetic fields and the radius of the capillary. Based on two discretization techniques, finite difference method (FDM) and finite element method (FEM), the set of integrated models are transformed into a series of grid points to get a large system of equations. The third model is a single cell density model involving the three sets of first order PDEs equations for proliferating, quiescent and necrotic cells change over time and space in Cartesian coordinate which regulates under different rates of nutrients consumptions. The model presents the proliferative and quiescent cell growth depends on some parameter changes and the necrotic cells emerged as the tumor core. Some numerical schemes for solving the system of equations are compared and analyzed. Simulation and computation of the discretized model are supported by Matlab and C programming languages on a single processing unit. Some numerical results and analysis of the algorithms are presented in terms of informative presentation of tables, multiple graph and multidimensional visualization. As a conclusion, the integrated of three types mathematical modeling and the comparison of numerical performance indicates that the superior tool and analysis for solving the complete set of magnetic drug delivery system which give significant effects on the growth of the targeted cancer cell.

Keywords: mathematical modeling, visualization, PDE models, magnetic nanoparticle drug delivery model, drug release model, single cell effects, avascular tumor growth, numerical analysis

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66 La0.80Ag0.15MnO3 Magnetic Nanoparticles for Self-Controlled Magnetic Fluid Hyperthermia

Authors: Marian Mihalik, Kornel Csach, Martin Kovalik, Matúš Mihalik, Martina Kubovčíková, Maria Zentková, Martin Vavra, Vladimír Girman, Jaroslav Briančin, Marija Perovic, Marija Boškovic, Magdalena Fitta, Robert Pelka

Abstract:

Current nanomaterials for use in biomedicine are based mainly on iron oxides and on present knowledge on magnetic nanostructures. Manganites can represent another material which can be used optionally. Manganites and their unique electronic properties have been extensively studied in the last decades not only due to fundamental interest but to possible applications of colossal magnetoresistance, magnetocaloric effect, and ferroelectric properties. It was found that the oxygen-reduction reaction on perovskite oxide is intimately connected with metal ion e.g., orbital occupation. The effect of oxygen deviation from the stoichiometric composition on crystal structure was studied very carefully by many authors on LaMnO₃. Depending on oxygen content, the crystal structure changes from orthorhombic one to rhombohedric for oxygen content 3.1. In the case of hole-doped manganites, the change from the orthorhombic crystal structure, which is typical for La1-xCaxMnO3 based manganites, to the rhombohedric crystal structure (La1-xMxMnO₃ where M = K, Ag, and Sr based materials) results in an enormous increase of the Curie temperature. In our paper, we study the effect of oxygen content on crystal structure, thermal, and magnetic properties (including magnetocaloric effect) of La1-xAgxMnO₃nano particle system. The content of oxygen in samples was tuned by heat treatment in different thermal regimes and in various environment (air, oxygen, argon). Water nanosuspensions based on La0.80Ag0.15MnO₃ magnetic particles with the Curie temperature of about 43oC were prepared by two different approaches. First, by using a laboratory circulation mill for milling of powder in the presence of sodium dodecyl sulphate (SDS) and subsequent centrifugation. Second nanosuspension was prepared using an agate bowl, etching in citric acid and HNO3, ultrasound homogeniser, centrifugation, and dextran 40 kDA or 15 kDA as surfactant. Electrostatic stabilisation obtained by the first approach did not offer long term kinetic and aggregation colloidal stability and was unable to compensate for attractive forces between particles under a magnetic field. By the second approach, we prepared suspension oversaturated by dextran 40 kDA for steric stabilisation, with evidence of the presence of superparamagnetic behaviour. Low concentration of nanoparticles and not ideal coverage of nanoparticles impacting the stability of ferrofluids was the disadvantage of this approach. Strong steric stabilisation was observable at alcaic conditions under pH = ~10. Application of dextran 15 kDA leads to relatively stable ferrofluid with pH around physiological conditions, but desegregation of powder by HNO₃ was not effective enough, and the average size of fragments was to large of about 150 nm, and we did not see any signature of superparamagnetic behaviour. The prepared ferrofluids were characterised by scanning and transition microscope method, thermogravimetry, magnetization, and AC susceptibility measurements. Specific Absorption Rate measurements were undertaken on powder as well on ferrofluids in order to estimate the potential application of La₀.₈₀Ag₀.₁₅MnO₃ magnetic particles based ferrofluid for hyperthermia. Our complex study contains an investigation of biocompatibility and potential biohazard of this material.

Keywords: manganites, magnetic nanoparticles, oxygen content, magnetic phase transition, magnetocaloric effect, ferrofluid, hyperthermia

Procedia PDF Downloads 63
65 A Computational Investigation of Potential Drugs for Cholesterol Regulation to Treat Alzheimer’s Disease

Authors: Marina Passero, Tianhua Zhai, Zuyi (Jacky) Huang

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Alzheimer’s disease has become a major public health issue, as indicated by the increasing populations of Americans living with Alzheimer’s disease. After decades of extensive research in Alzheimer’s disease, only seven drugs have been approved by Food and Drug Administration (FDA) to treat Alzheimer’s disease. Five of these drugs were designed to treat the dementia symptoms, and only two drugs (i.e., Aducanumab and Lecanemab) target the progression of Alzheimer’s disease, especially the accumulation of amyloid-b plaques. However, controversial comments were raised for the accelerated approvals of either Aducanumab or Lecanemab, especially with concerns on safety and side effects of these two drugs. There is still an urgent need for further drug discovery to target the biological processes involved in the progression of Alzheimer’s disease. Excessive cholesterol has been found to accumulate in the brain of those with Alzheimer’s disease. Cholesterol can be synthesized in both the blood and the brain, but the majority of biosynthesis in the adult brain takes place in astrocytes and is then transported to the neurons via ApoE. The blood brain barrier separates cholesterol metabolism in the brain from the rest of the body. Various proteins contribute to the metabolism of cholesterol in the brain, which offer potential targets for Alzheimer’s treatment. In the astrocytes, SREBP cleavage-activating protein (SCAP) binds to Sterol Regulatory Element-binding Protein 2 (SREBP2) in order to transport the complex from the endoplasmic reticulum to the Golgi apparatus. Cholesterol is secreted out of the astrocytes by ATP-Binding Cassette A1 (ABCA1) transporter. Lipoprotein receptors such as triggering receptor expressed on myeloid cells 2 (TREM2) internalize cholesterol into the microglia, while lipoprotein receptors such as Low-density lipoprotein receptor-related protein 1 (LRP1) internalize cholesterol into the neuron. Cytochrome P450 Family 46 Subfamily A Member 1 (CYP46A1) converts excess cholesterol to 24S-hydroxycholesterol (24S-OHC). Cholesterol has been approved for its direct effect on the production of amyloid-beta and tau proteins. The addition of cholesterol to the brain promotes the activity of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), secretase, and amyloid precursor protein (APP), which all aid in amyloid-beta production. The reduction of cholesterol esters in the brain have been found to reduce phosphorylated tau levels in mice. In this work, a computational pipeline was developed to identify the protein targets involved in cholesterol regulation in brain and further to identify chemical compounds as the inhibitors of a selected protein target. Since extensive evidence shows the strong correlation between brain cholesterol regulation and Alzheimer’s disease, a detailed literature review on genes or pathways related to the brain cholesterol synthesis and regulation was first conducted in this work. An interaction network was then built for those genes so that the top gene targets were identified. The involvement of these genes in Alzheimer’s disease progression was discussed, which was followed by the investigation of existing clinical trials for those targets. A ligand-protein docking program was finally developed to screen 1.5 million chemical compounds for the selected protein target. A machine learning program was developed to evaluate and predict the binding interaction between chemical compounds and the protein target. The results from this work pave the way for further drug discovery to regulate brain cholesterol to combat Alzheimer’s disease.

Keywords: Alzheimer’s disease, drug discovery, ligand-protein docking, gene-network analysis, cholesterol regulation

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64 Culture and Health Equity: Unpacking the Sociocultural Determinants of Eye Health for Indigenous Australian Diabetics

Authors: Aryati Yashadhana, Ted Fields Jnr., Wendy Fernando, Kelvin Brown, Godfrey Blitner, Francis Hayes, Ruby Stanley, Brian Donnelly, Bridgette Jerrard, Anthea Burnett, Anthony B. Zwi

Abstract:

Indigenous Australians experience some of the worst health outcomes globally, with life expectancy being significantly poorer than those of non-Indigenous Australians. This is largely attributed to preventable diseases such as diabetes (prevalence 39% in Indigenous Australian adults > 55 years), which is attributed to a raised risk of diabetic visual impairment and cataract among Indigenous adults. Our study aims to explore the interface between structural and sociocultural determinants and human agency, in order to understand how they impact (1) accessibility of eye health and chronic disease services and (2) the potential for Indigenous patients to achieve positive clinical eye health outcomes. We used Participatory Action Research methods, and aimed to privilege the voices of Indigenous people through community collaboration. Semi-structured interviews (n=82) and patient focus groups (n=8) were conducted by Indigenous Community-Based Researchers (CBRs) with diabetic Indigenous adults (> 40 years) in four remote communities in Australia. Interviews (n=25) and focus groups (n=4) with primary health care clinicians in each community were also conducted. Data were audio recorded, transcribed verbatim, and analysed thematically using grounded theory, comparative analysis and Nvivo 10. Preliminary analysis occurred in tandem with data collection to determine theoretical saturation. The principal investigator (AY) led analysis sessions with CBRs, fostering cultural and contextual appropriateness to interpreting responses, knowledge exchange and capacity building. Identified themes were conceptualised into three spheres of influence: structural (health services, government), sociocultural (Indigenous cultural values, distrust of the health system, ongoing effects of colonialism and dispossession) and individual (health beliefs/perceptions, patient phenomenology). Permeating these spheres of influence were three core determinants: economic disadvantage, health literacy/education, and cultural marginalisation. These core determinants affected accessibility of services, and the potential for patients to achieve positive clinical outcomes at every level of care (primary, secondary, tertiary). Our findings highlight the clinical realities of institutionalised and structural inequities, illustrated through the lived experiences of Indigenous patients and primary care clinicians in the four sampled communities. The complex determinants surrounding inequity in health for Indigenous Australians, are entrenched through a longstanding experience of cultural discrimination and ostracism. Secure and long term funding of Aboriginal Community Controlled Health Services will be valuable, but are insufficient to address issues of inequity. Rather, working collaboratively with communities to build trust, and identify needs and solutions at the grassroots level, while leveraging community voices to drive change at the systemic/policy level are recommended.

Keywords: indigenous, Australia, culture, public health, eye health, diabetes, social determinants of health, sociology, anthropology, health equity, aboriginal and Torres strait islander, primary care

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63 Pharmacokinetics of First-Line Tuberculosis Drugs in South African Patients from Kwazulu-Natal: Effects of Pharmacogenetic Variation on Rifampicin and Isoniazid Concentrations

Authors: Anushka Naidoo, Veron Ramsuran, Maxwell Chirehwa, Paolo Denti, Kogieleum Naidoo, Helen McIlleron, Nonhlanhla Yende-Zuma, Ravesh Singh, Sinaye Ngcapu, Nesri Padayatachi

Abstract:

Background: Despite efforts to introduce new drugs and shorter drug regimens for drug-susceptible tuberculosis (TB), the standard first-line treatment has not changed in over 50 years. Rifampicin, isoniazid, and pyrazinamide are critical components of the current standard treatment regimens. Some studies suggest that microbiologic failure and acquired drug resistance are primarily driven by low drug concentrations that result from pharmacokinetic (PK) variability independent of adherence to treatment. Wide between-patient pharmacokinetic variability for rifampin, isoniazid, and pyrazinamide has been reported in prior studies. There may be several reasons for this variability. However, genetic variability in genes coding for drug metabolizing and transporter enzymes have been shown to be a contributing factor for variable tuberculosis drug exposures. Objective: We describe the pharmacokinetics of first-line TB drugs rifampicin, isoniazid, and pyrazinamide and assess the effect of genetic variability in relevant selected drug metabolizing and transporter enzymes on pharmacokinetic parameters of isoniazid and rifampicin. Methods: We conducted the randomized-controlled Improving retreatment success TB trial in Durban, South Africa. The drug regimen included rifampicin, isoniazid, and pyrazinamide. Drug concentrations were measured in plasma, and concentration-time data were analysed using nonlinear-mixed-effects models to quantify the effects of relevant covariates and single nucleotide polymorphisms (SNP’s) of drug metabolizing and transporter genes on rifampicin, isoniazid and pyrazinamide exposure. A total of 25 SNP’s: four NAT2 (used to determine acetylator status), four SLCO1B1, three Pregnane X receptor (NR1), six ABCB1 and eight UGT1A, were selected for analysis in this study. Genotypes were determined for each of the SNP’s using a TaqMan® Genotyping OpenArray™. Results: Among fifty-eight patients studied; 41 (70.7%) were male, 97% black African, 42 (72.4%) HIV co-infected and 40 (95%) on efavirenz-based ART. Median weight, fat-free mass (FFM), and age at baseline were 56.9 kg (interquartile range, IQR: 51.1-65.2), 46.8 kg (IQR: 42.5-50.3) and 37 years (IQR: 31-42), respectively. The pharmacokinetics of rifampicin and pyrazinamide was best described using one-compartment models with first-order absorption and elimination, while for isoniazid two-compartment disposition was used. The median (interquartile range: IQR) AUC (h·mg/L) and Cmax (mg/L) for rifampicin, isoniazid, and pyrazinamide were; 25.62 (23.01-28.53) and 4.85 (4.36-5.40), 10.62 (9.20-12.25) and 2.79 (2.61-2.97), 345.74 (312.03-383.10) and 28.06 (25.01-31.52), respectively. Eighteen percent of patients were classified as rapid acetylators, and 34% and 43% as slow and intermediate acetylators, respectively. Rapid and intermediate acetylator status based on NAT 2 genotype resulted in 2.3 and 1.6 times higher isoniazid clearance than slow acetylators. We found no effects of the SLCO1B1 genotypes on rifampicin pharmacokinetics. Conclusion: Plasma concentrations of rifampicin, isoniazid, and pyrazinamide were low overall in our patients. Isoniazid clearance was high overall and as expected higher in rapid and intermediate acetylators resulting in lower drug exposures. In contrast to reports from previous South African or Ugandan studies, we did not find any effects of the SLCO1B1 or other genotypes tested on rifampicin PK. However, our findings are in keeping with more recent studies from Malawi and India emphasizing the need for geographically diverse and adequately powered studies. The clinical relevance of the low tuberculosis drug concentrations warrants further investigation.

Keywords: rifampicin, isoniazid pharmacokinetics, genetics, NAT2, SLCO1B1, tuberculosis

Procedia PDF Downloads 155
62 Benchmarking of Petroleum Tanker Discharge Operations at a Nigerian Coastal Terminal and Jetty Facilitates Optimization of the Ship–Shore Interface

Authors: Bassey O. Bassey

Abstract:

Benchmarking has progressively become entrenched as a requisite activity for process improvement and enhancing service delivery at petroleum jetties and terminals, most especially during tanker discharge operations at the ship – shore interface, as avoidable delays result in extra operating costs, non-productive time, high demurrage payments and ultimate product scarcity. The jetty and terminal in focus had been operational for 3 and 8 years respectively, with proper operational and logistic records maintained to evaluate their progress over time in order to plan and implement modifications and review of procedures for greater technical and economic efficiency. Regular and emergency staff meetings were held on a team, departmental and company-wide basis to progressively address major challenges that were encountered during each operation. The process and outcome of the resultant collectively planned changes carried out within the past two years forms the basis of this paper, which mirrors the initiatives effected to enhance operational and maintenance excellence at the affected facilities. Operational modifications included a second cargo receipt line designated for gasoline, product loss control at jetty and shore ends, enhanced product recovery and quality control, and revival of terminal–jetty backloading operations. Logistic improvements were the incorporation of an internal logistics firm and shipping agency, fast tracking of discharge procedures for tankers, optimization of tank vessel selection process, and third party product receipt and throughput. Maintenance excellence was achieved through construction of two new lay barges and refurbishment of the existing one; revamping of existing booster pump and purchasing of a modern one as reserve capacity; extension of Phase 1 of the jetty to accommodate two vessels and construction of Phase 2 for two more vessels; regular inspection, draining, drying and replacement of cargo hoses; corrosion management program for all process facilities; and an improved, properly planned and documented maintenance culture. Safety, environmental and security compliance were enhanced by installing state-of-the-art fire fighting facilities and equipment, seawater intake line construction as backup for borehole at the terminal, remediation of the shoreline and marine structures, modern spill containment equipment, improved housekeeping and accident prevention practices, and installation of hi-technology security enhancements, among others. The end result has been observed over the past two years to include improved tanker turnaround time, higher turnover on product sales, consistent product availability, greater indigenous human capacity utilisation by way of direct hires and contracts, as well as customer loyalty. The lessons learnt from this exercise would, therefore, serve as a model to be adapted by other operators of similar facilities, contractors, academics and consultants in a bid to deliver greater sustainability and profitability of operations at the ship – shore interface to this strategic industry.

Keywords: benchmarking, optimisation, petroleum jetty, petroleum terminal

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61 A Multimodal Discourse Analysis of Gender Representation on Health and Fitness Magazine Cover Pages

Authors: Nashwa Elyamany

Abstract:

In visual cultures, namely that of the United States, media representations are such influential and pervasive reflections of societal norms and expectations to the extent that they impact the manner in which both genders view themselves. Health and fitness magazines fall within the realm of visual culture. Since the main goal of communication is to ensure proper dissemination of information in order for the target audience to grasp the intended messages, it becomes imperative that magazine publishers, editors, advertisers and image producers use different modes of communication within their reach to convey messages to their readers and viewers. A rapid waxing flow of multimodality floods popular discourse, particularly health and fitness magazine cover pages. The use of well-crafted cover lines and visual images is imbued with agendas, consumerist ideologies and properties capable of effectively conveying implicit and explicit meaning to potential readers and viewers. In essence, the primary goal of this thesis is to interrogate the multi-semiotic operations and manifestations of hegemonic masculinity and femininity in male and female body culture, particularly on the cover pages of the twin American magazines Men's Health and Women's Health using corpora that spanned from 2011 to the mid of 2016. The researcher explores the semiotic resources that contribute to shaping and legitimizing a new form of postmodern, consumerist, gendered discourse that positions the reader-viewer ideologically. Methodologically, the researcher carries out analysis on the macro and micro levels. On the macro level, the researcher takes on a critical stance to illuminate the ideological nature of the multimodal ensemble of the cover pages, and, on the micro level, seeks to put forward new theoretical and methodological routes through which the semiotic choices well invested on the media texts can be more objectively scrutinized. On the macro level, a 'themes' analysis is initially conducted to isolate the overarching themes that dominate the fitness discourse on the cover pages under study. It is argued that variation in terms of frequencies of such themes is indicative, broadly speaking, of which facets of hegemonic masculinity and femininity are infused in the fitness discourse on the cover pages. On the micro level, this research work encompasses three sub-levels of analysis. The researcher follows an SF-MMDA approach, drawing on a trio of analytical frameworks: Halliday's SFG for the verbal analysis; Kress & van Leeuween's VG for the visual analysis; and CMT in relation to Sperber & Wilson's RT for the pragma-cognitive analysis of multimodal metaphors and metonymies. The data is presented in terms of detailed descriptions in conjunction with frequency tables, ANOVA with alpha=0.05 and MANOVA in the multiple phases of analysis. Insights and findings from this multi-faceted, social-semiotic analysis are interpreted in light of Cultivation Theory, Self-objectification Theory and the literature to date. Implications for future research include the implementation of a multi-dimensional approach whereby linguistic and visual analytical models are deployed with special regards to cultural variation.

Keywords: gender, hegemony, magazine cover page, multimodal discourse analysis, multimodal metaphor, multimodal metonymy, systemic functional grammar, visual grammar

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60 Transport Hubs as Loci of Multi-Layer Ecosystems of Innovation: Case Study of Airports

Authors: Carolyn Hatch, Laurent Simon

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Urban mobility and the transportation industry are undergoing a transformation, shifting from an auto production-consumption model that has dominated since the early 20th century towards new forms of personal and shared multi-modality [1]. This is shaped by key forces such as climate change, which has induced a shift in production and consumption patterns and efforts to decarbonize and improve transport services through, for instance, the integration of vehicle automation, electrification and mobility sharing [2]. Advanced innovation practices and platforms for experimentation and validation of new mobility products and services that are increasingly complex and multi-stakeholder-oriented are shaping this new world of mobility. Transportation hubs – such as airports - are emblematic of these disruptive forces playing out in the mobility industry. Airports are emerging as the core of innovation ecosystems on and around contemporary mobility issues, and increasingly recognized as complex public/private nodes operating in many societal dimensions [3,4]. These include urban development, sustainability transitions, digital experimentation, customer experience, infrastructure development and data exploitation (for instance, airports generate massive and often untapped data flows, with significant potential for use, commercialization and social benefit). Yet airport innovation practices have not been well documented in the innovation literature. This paper addresses this gap by proposing a model of airport innovation that aims to equip airport stakeholders to respond to these new and complex innovation needs in practice. The methodology involves: 1 – a literature review bringing together key research and theory on airport innovation management, open innovation and innovation ecosystems in order to evaluate airport practices through an innovation lens; 2 – an international benchmarking of leading airports and their innovation practices, including such examples as Aéroports de Paris, Schipol in Amsterdam, Changi in Singapore, and others; and 3 – semi-structured interviews with airport managers on key aspects of organizational practice, facilitated through a close partnership with the Airport Council International (ACI), a major stakeholder in this research project. Preliminary results find that the most successful airports are those that have shifted to a multi-stakeholder, platform ecosystem model of innovation. The recent entrance of new actors in airports (Google, Amazon, Accor, Vinci, Airbnb and others) have forced the opening of organizational boundaries to share and exchange knowledge with a broader set of ecosystem players. This has also led to new forms of governance and intermediation by airport actors to connect complex, highly distributed knowledge, along with new kinds of inter-organizational collaboration, co-creation and collective ideation processes. Leading airports in the case study have demonstrated a unique capacity to force traditionally siloed activities to “think together”, “explore together” and “act together”, to share data, contribute expertise and pioneer new governance approaches and collaborative practices. In so doing, they have successfully integrated these many disruptive change pathways and forced their implementation and coordination towards innovative mobility outcomes, with positive societal, environmental and economic impacts. This research has implications for: 1 - innovation theory, 2 - urban and transport policy, and 3 - organizational practice - within the mobility industry and across the economy.

Keywords: airport management, ecosystem, innovation, mobility, platform, transport hubs

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59 Black-Box-Optimization Approach for High Precision Multi-Axes Forward-Feed Design

Authors: Sebastian Kehne, Alexander Epple, Werner Herfs

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A new method for optimal selection of components for multi-axes forward-feed drive systems is proposed in which the choice of motors, gear boxes and ball screw drives is optimized. Essential is here the synchronization of electrical and mechanical frequency behavior of all axes because even advanced controls (like H∞-controls) can only control a small part of the mechanical modes – namely only those of observable and controllable states whose value can be derived from the positions of extern linear length measurement systems and/or rotary encoders on the motor or gear box shafts. Further problems are the unknown processing forces like cutting forces in machine tools during normal operation which make the estimation and control via an observer even more difficult. To start with, the open source Modelica Feed Drive Library which was developed at the Laboratory for Machine Tools, and Production Engineering (WZL) is extended from one axis design to the multi axes design. It is capable to simulate the mechanical, electrical and thermal behavior of permanent magnet synchronous machines with inverters, different gear boxes and ball screw drives in a mechanical system. To keep the calculation time down analytical equations are used for field and torque producing equivalent circuit, heat dissipation and mechanical torque at the shaft. As a first step, a small machine tool with a working area of 635 x 315 x 420 mm is taken apart, and the mechanical transfer behavior is measured with an impulse hammer and acceleration sensors. With the frequency transfer functions, a mechanical finite element model is built up which is reduced with substructure coupling to a mass-damper system which models the most important modes of the axes. The model is modelled with Modelica Feed Drive Library and validated by further relative measurements between machine table and spindle holder with a piezo actor and acceleration sensors. In a next step, the choice of possible components in motor catalogues is limited by derived analytical formulas which are based on well-known metrics to gain effective power and torque of the components. The simulation in Modelica is run with different permanent magnet synchronous motors, gear boxes and ball screw drives from different suppliers. To speed up the optimization different black-box optimization methods (Surrogate-based, gradient-based and evolutionary) are tested on the case. The objective that was chosen is to minimize the integral of the deviations if a step is given on the position controls of the different axes. Small values are good measures for a high dynamic axes. In each iteration (evaluation of one set of components) the control variables are adjusted automatically to have an overshoot less than 1%. It is obtained that the order of the components in optimization problem has a deep impact on the speed of the black-box optimization. An approach to do efficient black-box optimization for multi-axes design is presented in the last part. The authors would like to thank the German Research Foundation DFG for financial support of the project “Optimierung des mechatronischen Entwurfs von mehrachsigen Antriebssystemen (HE 5386/14-1 | 6954/4-1)” (English: Optimization of the Mechatronic Design of Multi-Axes Drive Systems).

Keywords: ball screw drive design, discrete optimization, forward feed drives, gear box design, linear drives, machine tools, motor design, multi-axes design

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58 The Shrinking of the Pink Wave and the Rise of the Right-Wing in Latin America

Authors: B. M. Moda, L. F. Secco

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Through free and fair elections and others less democratic processes, Latin America has been gradually turning into a right-wing political region. In order to understand these recent changes, this paper aims to discuss the origin and the traits of the pink wave in the subcontinent, the reasons for its current rollback and future projections for left-wing in the region. The methodology used in this paper will be descriptive and analytical combined with secondary sources mainly from the social and political sciences fields. The canons of the Washington Consensus was implemented by the majority of the Latin American governments in the 80s and 90s under the social democratic and right-wing parties. The neoliberal agenda caused political, social and economic dissatisfaction bursting into a new political configuration for the region. It started in 1998 when Hugo Chávez took the office in Venezuela through the Fifth Republic Movement under the socialist flag. From there on, Latin America was swiped by the so-called ‘pink wave’, term adopted to define the rising of self-designated left-wing or center-left parties with a progressive agenda. After Venezuela, countries like Chile, Brazil, Argentina, Uruguay, Bolivia, Equator, Nicaragua, Paraguay, El Salvador and Peru got into the pink wave. The success of these governments was due a post-neoliberal agenda focused on cash transfers programs, increasing of public spending, and the straightening of national market. The discontinuation of the preference for the left-wing started in 2012 with the coup against Fernando Lugo in Paraguay. In 2015, the chavismo in Venezuela lost the majority of the legislative seats. In 2016, an impeachment removed the Brazilian president Dilma Rousself from office who was replaced by the center-right vice-president Michel Temer. In the same year, Mauricio Macri representing the right-wing party Proposta Republicana was elected in Argentina. In 2016 center-right and liberal, Pedro Pablo Kuczynski was elected in Peru. In 2017, Sebastián Piñera was elected in Chile through the center-right party Renovación Nacional. The pink wave current rollback points towards some findings that can be arranged in two fields. Economically, the 2008 financial crisis affected the majority of the Latin American countries and the left-wing economic policies along with the end of the raw materials boom and the subsequent shrinking of economic performance opened a flank for popular dissatisfaction. In Venezuela, the 2014 oil crisis reduced the revenues for the State in more than 50% dropping social spending, creating an inflationary spiral, and consequently loss of popular support. Politically, the death of Hugo Chavez in 2013 weakened the ‘socialism of the twenty first century’ ideal, which was followed by the death of Fidel Castro, the last bastion of communism in the subcontinent. In addition, several cases of corruption revealed during the pink wave governments made the traditional politics unpopular. These issues challenge the left-wing to develop a future agenda based on innovation of its economic program, improve its legal and political compliance practices, and to regroup its electoral forces amid the social movements that supported its ascension back in the early 2000s.

Keywords: Latin America, political parties, left-wing, right-wing, pink wave

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57 Implementation of Autologous Adipose Graft from the Abdomen for Complete Fat Pad Loss of the Heel Following a Traumatic Open Fracture Secondary to a Motor Vehicle Accident: A Case Study

Authors: Ahmad Saad, Shuja Abbas, Breanna Marine

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Introduction: This study explores the potential applications of autologous pedal fat pad grafting as a minimally invasive therapeutic strategy for addressing pedal fat pad loss. Without adequate shock absorbing tissue, a patient can experience functional deficits, ulcerations, loss of quality of life, and significant limitations with ambulation. This study details a novel technique involving autologous adipose grafting from the abdomen to enhance plantar fat pad thickness in a patient involved in a severe motor vehicle accident which resulted in total fat pad loss of the heel. Autologous adipose grafting (AAG) was used following adipose allografting in an effort to recreate a normal shock absorbing surface to allow return to activities of daily living and painless ambulation. Methods: A 46-year-old male sustained multiple open pedal fractures and necrosis to the heel fat pad after a motorcycle accident, which resulted in complete loss of the calcaneal fat pad. The patient underwent serial debridement’s, utilization of wound vac therapy and split thickness skin grafting to accomplish complete closure, despite complete loss of adipose to area. Patient presented with complaints of pain on ambulation, inability to bear weight on the heel, recurrent ulcerations, admitted had not been ambulating for two years. Clinical exam demonstrated complete loss of the plantar fat pad with a thin layer of epithelial tissue overlying the calcaneal bone, allowing visibility of the osseous contour of the calcaneus. Scar tissue had formed in place of the fat pad, with thickened epithelial tissue extending from the midfoot to the calcaneus. After conservative measures were exhausted, the patient opted for initial management by adipose allograft matrix (AAM) injections. Post operative X-ray imaging revealed noticeable improvement in calcaneal fat pad thickness. At 1 year follow up, the patient was able to ambulate without assistive devices. The fat pad at this point was significantly thicker than it was pre-operatively, but the thickness did not restore to pre-accident thickness. In order to compare the take of allograft versus autografting of adipose tissue, the decision to use adipose autograft through abdominal liposuction harvesting was deemed suitable. A general surgeon completed harvesting of adipose cells from the patient’s abdomen via liposuction, and a podiatric surgeon performed the AAG injection into the heel. Total of 15 cc’s of autologous adipose tissue injected to the calcaneus. Results: There was a visual increase in the calcaneal fat pad thickness both clinically and radiographically. At the 6-week follow up, imaging revealed retention of the calcaneal fat pad thickness. Three months postop, patient returned to activities of daily living and increased quality of life due to their increased ability to ambulate. Discussion: AAG is a novel treatment for pedal fat pad loss. These treatments may be viable and reproducible therapeutic choices for patients suffering from fat pad atrophy, fat pad loss, and/or plantar ulcerations. Both treatments of AAM and AAG exhibited similar therapeutic results by providing pain relief for ambulation and allowing for patients to return to their quality of life.

Keywords: podiatry, wound, adipose, allograft, autograft, wound care, limb reconstruction, injection, limb salvage

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56 Action Research-Informed Multiliteracies-Enhanced Pedagogy in an Online English for Academic Purposes Course

Authors: Heejin Song

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Employing a critical action research approach that rejects essentialist onto-epistemological orientations to research in English language teaching (ELT) and interrogates the hegemonic relations in the knowledge construction and reconstruction processes, this study illuminates how an action research-informed pedagogical practice can transform the English for academic purposes (EAP) teaching to be more culturally and linguistically inclusive and critically oriented for English language learners’ advancement in academic literacies skills. More specifically, this paper aims to showcase the action research-informed pedagogical innovations that emphasize multilingual learners’ multiliteracies engagement and experiential education-oriented learning to facilitate the development of learners’ academic literacies, intercultural communicative competence, and inclusive global citizenship in the context of Canadian university EAP classrooms. The pedagogical innovations through action research embarked in response to growing discussions surrounding pedagogical possibilities of plurilingualism in ELT and synchronous online teaching. The paper is based on two iterations of action research over the pandemic years between 2020 and 2022. The data includes student work samples, focus group interviews, anonymous surveys, teacher feedback and comments on student work and teaching reflections. The first iteration of the action research focused on the affordances of multimodal expressions in individual learners’ academic endeavors for their literacy skills development through individual online activities such as ‘my language autobiography,’ ‘multimodal expression corner’ and public speeches. While these activities help English language learners enhance their knowledge and skills of English-spoken discourses, these tasks did not necessarily require learners’ team-based collaborative endeavors to complete the assigned tasks. Identifying this area for improvement in the instructional design, the second action research cycle/iteration emphasized collaborative performativity through newly added performance/action-based innovative learning tasks, including ‘situational role-playing’, ‘my cooking show & interview’, and group debates in order to provide learners increased opportunities to communicate with peers who joined the class virtually from different parts of the world and enhance learners’ intercultural competence through various strategic and pragmatic communicative skills to collaboratively achieve their shared goals (i.e., successful completion of the given group tasks). The paper exemplifies instances wherein learners’ unique and diverse linguistic and cultural strengths were amplified, and critical literacies were further developed through learners’ performance-oriented multiliteracies engagement. The study suggests that the action research-informed teaching practice that advocates for collaborative multiliteracies engagement serves to facilitate learners’ activation of their existing linguistic and cultural knowledge and contributes to the development of learners’ academic literacy skills. Importantly, the study illuminates that such action research-informed pedagogical initiatives create an inclusive space for learners to build a strong sense of connectedness as global citizens with increased intercultural awareness in their community of language and cultural practices, and further allow learners to actively participate in the construction of ‘collaborative relations of power’ with their peers.

Keywords: action research, EAP, higher education, multiliteracies

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55 Understanding the Impact of Spatial Light Distribution on Object Identification in Low Vision: A Pilot Psychophysical Study

Authors: Alexandre Faure, Yoko Mizokami, éRic Dinet

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These recent years, the potential of light in assisting visually impaired people in their indoor mobility has been demonstrated by different studies. Implementing smart lighting systems for selective visual enhancement, especially designed for low-vision people, is an approach that breaks with the existing visual aids. The appearance of the surface of an object is significantly influenced by the lighting conditions and the constituent materials of the objects. Appearance of objects may appear to be different from expectation. Therefore, lighting conditions lead to an important part of accurate material recognition. The main objective of this work was to investigate the effect of the spatial distribution of light on object identification in the context of low vision. The purpose was to determine whether and what specific lighting approaches should be preferred for visually impaired people. A psychophysical experiment was designed to study the ability of individuals to identify the smallest cube of a pair under different lighting diffusion conditions. Participants were divided into two distinct groups: a reference group of observers with normal or corrected-to-normal visual acuity and a test group, in which observers were required to wear visual impairment simulation glasses. All participants were presented with pairs of cubes in a "miniature room" and were instructed to estimate the relative size of the two cubes. The miniature room replicates real-life settings, adorned with decorations and separated from external light sources by black curtains. The correlated color temperature was set to 6000 K, and the horizontal illuminance at the object level at approximately 240 lux. The objects presented for comparison consisted of 11 white cubes and 11 black cubes of different sizes manufactured with a 3D printer. Participants were seated 60 cm away from the objects. Two different levels of light diffuseness were implemented. After receiving instructions, participants were asked to judge whether the two presented cubes were the same size or if one was smaller. They provided one of five possible answers: "Left one is smaller," "Left one is smaller but unsure," "Same size," "Right one is smaller," or "Right one is smaller but unsure.". The method of constant stimuli was used, presenting stimulus pairs in a random order to prevent learning and expectation biases. Each pair consisted of a comparison stimulus and a reference cube. A psychometric function was constructed to link stimulus value with the frequency of correct detection, aiming to determine the 50% correct detection threshold. Collected data were analyzed through graphs illustrating participants' responses to stimuli, with accuracy increasing as the size difference between cubes grew. Statistical analyses, including 2-way ANOVA tests, showed that light diffuseness had no significant impact on the difference threshold, whereas object color had a significant influence in low vision scenarios. The first results and trends derived from this pilot experiment clearly and strongly suggest that future investigations could explore extreme diffusion conditions to comprehensively assess the impact of diffusion on object identification. For example, the first findings related to light diffuseness may be attributed to the range of manipulation, emphasizing the need to explore how other lighting-related factors interact with diffuseness.

Keywords: Lighting, Low Vision, Visual Aid, Object Identification, Psychophysical Experiment

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54 Biochemical and Antiviral Study of Peptides Isolated from Amaranthus hypochondriacus on Tomato Yellow Leaf Curl Virus Replication

Authors: José Silvestre Mendoza Figueroa, Anders Kvarnheden, Jesús Méndez Lozano, Edgar Antonio Rodríguez Negrete, Manuel Soriano García

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Agroindustrial plants such as cereals and pseudo cereals offer a substantial source of biomacromolecules, as they contain large amounts per tissue-gram of proteins, polysaccharides and lipids in comparison with other plants. In particular, Amaranthus hypochondriacus seeds have high levels of proteins in comparison with other cereal and pseudo cereal species, which makes the plant a good source of bioactive molecules such as peptides. Geminiviruses are one principal class of pathogens that causes important economic losses in crops, affecting directly the development and production of the plant. One such virus is the Tomato yellow leaf curl virus (TYLCV), which affects mainly Solanacea family plants such as tomato species. The symptoms of the disease are curling of leaves, chlorosis, dwarfing and floral abortion. The aim of this work was to get peptides derived from enzymatic hydrolysis of globulins and albumins from amaranth seeds with specific recognition of the replication origin in the TYLCV genome, and to test the antiviral activity on host plants with the idea to generate a direct control of this viral infection. Globulins and albumins from amaranth were extracted, the fraction was enzymatically digested with papain, and the aromatic peptides fraction was selected for further purification. Six peptides were tested against the replication origin (OR) using affinity assays, surface resonance plasmon and fluorescent titration, and two of these peptides showed high affinity values to the replication origin of the virus, dissociation constant values were calculated and showed specific interaction between the peptide Ampep1 and the OR. An in vitro replication test of the total TYLCV DNA was performed, in which the peptide AmPep1 was added in different concentrations to the system reaction, which resulted in a decrease of viral DNA synthesis when the peptide concentration increased. Also, we showed that the peptide can decrease the complementary DNA chain of the virus in Nicotiana benthamiana leaves, confirming that the peptide binds to the OR and that its expected mechanism of action is to decrease the replication rate of the viral genome. In an infection assay, N. benthamiana plants were agroinfected with TYLCV-Israel and TYLCV-Guasave. After confirming systemic infection, the peptide was infiltrated in new infected leaves, and the plants treated with the peptide showed a decrease of virus symptoms and viral titer. In order to confirm the antiviral activity in a commercial crop, tomato plants were infected with TYLCV. After confirming systemic infection, plants were infiltrated with peptide solution as above, and the symptom development was monitored 21 days after treatment, showing that tomato plants treated with peptides had lower symptom rates and viral titer. The peptide was also tested against other begomovirus such as Pepper huasteco yellow vein virus (PHYVV-Guasave), showing a decrease of symptoms in N. benthamiana infected plants. The model of direct biochemical control of TYLCV infection shown in this work can be extrapolated to other begomovirus infections, and the methods reported here can be used for design of antiviral agrochemicals for other plant virus infections.

Keywords: agrochemical screening, antiviral, begomovirus, geminivirus, peptides, plasmon, TYLCV

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53 Neural Correlates of Diminished Humor Comprehension in Schizophrenia: A Functional Magnetic Resonance Imaging Study

Authors: Przemysław Adamczyk, Mirosław Wyczesany, Aleksandra Domagalik, Artur Daren, Kamil Cepuch, Piotr Błądziński, Tadeusz Marek, Andrzej Cechnicki

Abstract:

The present study aimed at evaluation of neural correlates of humor comprehension impairments observed in schizophrenia. To investigate the nature of this deficit in schizophrenia and to localize cortical areas involved in humor processing we used functional magnetic resonance imaging (fMRI). The study included chronic schizophrenia outpatients (SCH; n=20), and sex, age and education level matched healthy controls (n=20). The task consisted of 60 stories (setup) of which 20 had funny, 20 nonsensical and 20 neutral (not funny) punchlines. After the punchlines were presented, the participants were asked to indicate whether the story was comprehensible (yes/no) and how funny it was (1-9 Likert-type scale). fMRI was performed on a 3T scanner (Magnetom Skyra, Siemens) using 32-channel head coil. Three contrasts in accordance with the three stages of humor processing were analyzed in both groups: abstract vs neutral stories - incongruity detection; funny vs abstract - incongruity resolution; funny vs neutral - elaboration. Additionally, parametric modulation analysis was performed using both subjective ratings separately in order to further differentiate the areas involved in incongruity resolution processing. Statistical analysis for behavioral data used U Mann-Whitney test and Bonferroni’s correction, fMRI data analysis utilized whole-brain voxel-wise t-tests with 10-voxel extent threshold and with Family Wise Error (FWE) correction at alpha = 0.05, or uncorrected at alpha = 0.001. Between group comparisons revealed that the SCH subjects had attenuated activation in: the right superior temporal gyrus in case of irresolvable incongruity processing of nonsensical puns (nonsensical > neutral); the left medial frontal gyrus in case of incongruity resolution processing of funny puns (funny > nonsensical) and the interhemispheric ACC in case of elaboration of funny puns (funny > neutral). Additionally, the SCH group revealed weaker activation during funniness ratings in the left ventro-medial prefrontal cortex, the medial frontal gyrus, the angular and the supramarginal gyrus, and the right temporal pole. In comprehension ratings the SCH group showed suppressed activity in the left superior and medial frontal gyri. Interestingly, these differences were accompanied by protraction of time in both types of rating responses in the SCH group, a lower level of comprehension for funny punchlines and a higher funniness for absurd punchlines. Presented results indicate that, in comparison to healthy controls, schizophrenia is characterized by difficulties in humor processing revealed by longer reaction times, impairments of understanding jokes and finding nonsensical punchlines more funny. This is accompanied by attenuated brain activations, especially in the left fronto-parietal and the right temporal cortices. Disturbances of the humor processing seem to be impaired at the all three stages of the humor comprehension process, from incongruity detection, through its resolution to elaboration. The neural correlates revealed diminished neural activity of the schizophrenia brain, as compared with the control group. The study was supported by the National Science Centre, Poland (grant no 2014/13/B/HS6/03091).

Keywords: communication skills, functional magnetic resonance imaging, humor, schizophrenia

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