Search results for: Evelyn Gnanam William George

Authors: Amber Dhoot, Tarush Gupta, Andrea Gurr, William Jenkins, Sandro Pietrunti, Alexis Tang

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Background: The COVID-19 pandemic has driven pharmacovigilance towards a new paradigm. Nowadays, more people than ever before are recognising and reporting adverse reactions from medications, treatments, and vaccines. In the modern era, with over 3.8 billion users, social media has become the most accessible medium for people to voice their opinions and so provides an opportunity to engage with more patient-centric and accessible pharmacovigilance. However, the pharmaceutical industry has been slow to incorporate social media into its modern pharmacovigilance strategy. This project aims to make social media a more effective tool in pharmacovigilance, and so reduce drug costs, improve drug safety and improve patient outcomes. This will be achieved by firstly uncovering and categorising the barriers facing the widespread adoption of social media in pharmacovigilance. Following this, the potential opportunities of social media will be explored. We will then propose realistic, practical recommendations to make social media a more effective tool for pharmacovigilance. Methodology: A comprehensive systematic literature review was conducted to produce a categorised summary of these barriers. This was followed by conducting 11 semi-structured interviews with pharmacovigilance experts to confirm the literature review findings whilst also exploring the unpublished and real-life challenges faced by those in the pharmaceutical industry. Finally, a survey of the general public (n = 112) ascertained public knowledge, perception, and opinion regarding the use of their social media data for pharmacovigilance purposes. This project stands out by offering perspectives from the public and pharmaceutical industry that fill the research gaps identified in the literature review. Results: Our results gave rise to several key analysis points. Firstly, inadequacies of current Natural Language Processing algorithms hinder effective pharmacovigilance data extraction from social media, and where data extraction is possible, there are significant questions over its quality. Social media also contains a variety of biases towards common drugs, mild adverse drug reactions, and the younger generation. Additionally, outdated regulations for social media pharmacovigilance do not align with new, modern General Data Protection Regulations (GDPR), creating ethical ambiguity about data privacy and level of access. This leads to an underlying mindset of avoidance within the pharmaceutical industry, as firms are disincentivised by the legal, financial, and reputational risks associated with breaking ambiguous regulations. Conclusion: Our project uncovered several barriers that prevent effective pharmacovigilance on social media. As such, social media should be used to complement traditional sources of pharmacovigilance rather than as a sole source of pharmacovigilance data. However, this project adds further value by proposing five practical recommendations that improve the effectiveness of social media pharmacovigilance. These include: prioritising health-orientated social media; improving technical capabilities through investment and strategic partnerships; setting clear regulatory guidelines using multi-stakeholder processes; creating an adverse drug reaction reporting interface inbuilt into social media platforms; and, finally, developing educational campaigns to raise awareness of the use of social media in pharmacovigilance. Implementation of these recommendations would speed up the efficient, ethical, and systematic adoption of social media in pharmacovigilance.

Keywords: adverse drug reaction, drug safety, pharmacovigilance, social media

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Authors: Karlee J. Hall, Mark Laylor, Jessy Varghese, Paula Polastri, Karen Van Ooteghem, William McIlroy

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Balance training is a common part of physiotherapy treatment and often involves a set of proprioceptive exercises which the patient carries out in the clinic and as part of their exercise program. Understanding all contributing factors to altered balance is of utmost importance to the clinical success of treatment of balance dysfunctions. A critical role for the autonomic nervous system (ANS) in the control of balance reactions has been proposed previously, with evidence for potential involvement being inferred from the observation of phasic galvanic skin responses (GSR) evoked by external balance perturbations. The current study explored whether the coupling between ANS reactivity and balance reactions would be observed during spontaneously occurring instability while standing, including standard positions typical of physiotherapy balance assessments. It was hypothesized that time-varying changes in GSR (ANS reactivity) would be associated with time-varying changes in the mediolateral center of pressure (ML-COP) (somatomotor reactivity). Nine individuals (5 females, 4 males, aged 19-37 years) were recruited. To induce varying balance demands during standing, the study compared ML-COP and GSR data across different task conditions varying the availability of vision and width of the base of support. Subjects completed 3, 30-second trials for each of the following stance conditions: standard, narrow, and tandem eyes closed, tandem eyes open, tandem eyes open with dome to shield visual input, and restricted peripheral visual field. ANS activity was evaluated by measures of GSR recorded from Ag-AgCl electrodes on the middle phalanges of digits 2 and 4 on the left hand; balance measures include ML-COP excursion frequency and amplitude recorded from two force plates embedded in the floor underneath each foot. Subjects were instructed to stand as still as possible with arms crossed in front of their chest. When comparing mean task differences across subjects, there was an expected increase in postural sway from tasks with a wide stance and no sensory restrictions (least challenging) to those with a narrow stance and no vision (most challenging). The correlation analysis revealed a significant positive relationship between ML-COP variability and GSR variability when comparing across tasks (r=0.94, df=5, p < 0.05). In addition, correlations coincided within each subject and revealed a significant positive correlation in 7 participants (r= 0.47, 0.57, 0.62, 0.62, 0.81, 0.64, 0.69 respectively, df=19, p < 0.05) and no significant relationship in 2 participants (r=0.36, 0.29 respectively, df=19, p > 0.05). The current study revealed a significant relationship between ML-COP and GSR during balance tasks, revealing the ANS reactivity associated with naturally occurring instability when standing still, which is proportional to the degree of instability. Understanding the link between ANS activity and control of COP is an important step forward in the enhancement of assessment of contributing factors to poor balance and treatment of balance dysfunctions. The next steps will explore the temporal association between the time-varying changes in COP and GSR to establish if the ANS reactivity phase leads or lags the evoked motor reactions, as well as exploration of potential biomarkers for use in screening of ANS activity as a contributing factor to altered balance control clinically.

Keywords: autonomic nervous system, balance control, center of pressure, somatic nervous system

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Authors: George Zhou, Yunchan Chen, Candace Chien

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Kidney replacement therapy is the current standard of care for end-stage renal diseases. In-center or home hemodialysis remains an integral component of the therapeutic regimen. Arteriovenous fistulas (AVF) make up the vascular circuit through which blood is filtered and returned. Naturally, AVF patency determines whether adequate clearance and filtration can be achieved and directly influences clinical outcomes. Our aim was to build a deep learning model for automated AVF stenosis screening based on the sound of blood flow through the AVF. A total of 311 patients with AVF were enrolled in this study. Blood flow sounds were collected using a digital stethoscope. For each patient, blood flow sounds were collected at 6 different locations along the patient’s AVF. The 6 locations are artery, anastomosis, distal vein, middle vein, proximal vein, and venous arch. A total of 1866 sounds were collected. The blood flow sounds are labeled as “patent” (normal) or “stenotic” (abnormal). The labels are validated from concurrent ultrasound. Our dataset included 1527 “patent” and 339 “stenotic” sounds. We show that blood flow sounds vary significantly along the AVF. For example, the blood flow sound is loudest at the anastomosis site and softest at the cephalic arch. Contextualizing the sound with location metadata significantly improves classification performance. How to encode and incorporate categorical metadata is an active area of research1. Herein, we study ordinal (i.e., integer) encoding schemes. The numerical representation is concatenated to the flattened feature vector. We train a vision transformer (ViT) on spectrogram image representations of the sound and demonstrate that using scalar multiples of our integer encodings improves classification performance. Models are evaluated using a 10-fold cross-validation procedure. The baseline performance of our ViT without any location metadata achieves an AuROC and AuPRC of 0.68 ± 0.05 and 0.28 ± 0.09, respectively. Using the following encodings of Artery:0; Arch: 1; Proximal: 2; Middle: 3; Distal 4: Anastomosis: 5, the ViT achieves an AuROC and AuPRC of 0.69 ± 0.06 and 0.30 ± 0.10, respectively. Using the following encodings of Artery:0; Arch: 10; Proximal: 20; Middle: 30; Distal 40: Anastomosis: 50, the ViT achieves an AuROC and AuPRC of 0.74 ± 0.06 and 0.38 ± 0.10, respectively. Using the following encodings of Artery:0; Arch: 100; Proximal: 200; Middle: 300; Distal 400: Anastomosis: 500, the ViT achieves an AuROC and AuPRC of 0.78 ± 0.06 and 0.43 ± 0.11. respectively. Interestingly, we see that using increasing scalar multiples of our integer encoding scheme (i.e., encoding “venous arch” as 1,10,100) results in progressively improved performance. In theory, the integer values do not matter since we are optimizing the same loss function; the model can learn to increase or decrease the weights associated with location encodings and converge on the same solution. However, in the setting of limited data and computation resources, increasing the importance at initialization either leads to faster convergence or helps the model escape a local minimum.

Keywords: arteriovenous fistula, blood flow sounds, metadata encoding, deep learning

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Authors: Albert Mufundirwa, Satoru Yoshioka, K. Ogi, Takeharu Sugiyama, George F. Harrington, Bretislav Smid, Benjamin Cunning, Kazunari Sasaki, Akari Hayashi, Stephen M. Lyth

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Polymer electrolyte membrane fuel cells (PEMFCs) are electrochemical energy conversion devices used for portable, residential and vehicular applications due to their low emissions, high efficiency, and quick start-up characteristics. However, PEMFCs generally use expensive, Pt-based electrocatalysts as electrode catalysts. Due to the high cost and limited availability of platinum, research and development to either drastically reduce platinum loading, or replace platinum with alternative catalysts is of paramount importance. A combination of high surface area supports and nano-structured active sites is essential for effective operation of catalysts. We synthesize carbon foam supports by thermal decomposition of sodium ethoxide, using a template-free, gram scale, cheap, and scalable pyrolysis method. This carbon foam has a high surface area, highly porous, three-dimensional framework which is ideal for electrochemical applications. These carbon foams can have surface area larger than 2500 m²/g, and electron microscopy reveals that they have micron-scale cells, separated by few-layer graphene-like carbon walls. We applied this carbon foam as a platinum catalyst support, resulting in the improved electrochemical surface area and mass activity for the oxygen reduction reaction (ORR), compared to carbon black. Similarly, silver-decorated carbon foams showed higher activity and efficiency for electrochemical carbon dioxide conversion than silver-decorated carbon black. A promising alternative to Pt-catalysts for the ORR is iron-impregnated nitrogen-doped carbon catalysts (Fe-N-C). Doping carbon with nitrogen alters the chemical structure and modulates the electronic properties, allowing a degree of control over the catalytic properties. We have adapted our synthesis method to produce nitrogen-doped carbon foams with large surface area, using triethanolamine as a nitrogen feedstock, in a novel bottom-up protocol. These foams are then infiltrated with iron acetate (FeAc) and pyrolysed to form Fe-N-C foams. The resulting Fe-N-C foam catalysts have high initial activity (half-wave potential of 0.68 VRHE), comparable to that of commercially available Pt-free catalysts (e.g., NPC-2000, Pajarito Powder) in acid solution. In alkaline solution, the Fe-N-C carbon foam catalysts have a half-wave potential of 0.89 VRHE, which is higher than that of NPC-2000 by almost 10 mVRHE, and far out-performing platinum. However, the durability is still a problem at present. The lessons learned from X-ray absorption spectroscopy (XAS), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and electrochemical measurements will be used to carefully design Fe-N-C catalysts for higher performance PEMFCs.

Keywords: carbon-foam, polymer electrolyte membrane fuel cells, platinum, Pt-free, Fe-N-C, ORR

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Authors: Christabel Ihedike, John Mooney, Monica Price

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Summary: This study aims to critically evaluate effect of photochemical smog on respiratory health in Nigeria. Cohort of chronic obstructive pulmonary disease (COPD) patients was recruited from two large hospitals in Abuja Nigeria. Respiratory health questionnaires, daily diaries, dyspnoea scale and lung function measurement were used to obtain health data and investigate the relationship with air quality data (principally ozone, NOx and particulate pollution). Concentrations of air pollutants were higher than WHO and Nigerian air quality standard. The result suggests a correlation between measured air quality and exacerbation of respiratory illness. Introduction: Photochemical smog is a significant health challenge in most cities and its effect on respiratory health is well acknowledged. This type of pollution is most harmful to the elderly, children and those with underlying respiratory disease. This study aims to investigate impact of increasing temperature and photo-chemically generated secondary air pollutants on respiratory health in Abuja Nigeria. Method and Result: Health data was collected using spirometry to measure lung function on routine attendance at the clinic, daily diaries kept by patients and information obtained using respiratory questionnaire. Questionnaire responses (obtained using an adapted and internally validated version of St George’s Hospital Respiratory Questionnaire), shows that ‘time of wheeze’ showed an association with participants activities: 30% had worse wheeze in the morning: 10% cannot shop, 15% take long-time to get washed, 25% walk slower, 15% if hurry have to stop and 5% cannot take-bath. There was also a decrease in Forced expiratory volume in the first second and Forced Vital Capacity, and daily change in the afternoon–morning may be associated with the concentration level of pollutants. Also, dyspnoea symptoms recorded that 60% of patients were on grade 3, 25% grade 2 and 15% grade 1. Daily frequency of the number of patients in the cohort that cough /brought sputum is 78%. Air pollution in the city is higher than Nigerian and WHO standards with NOx and PM10 concentrations of 693.59ug/m-3 and 748ugm-3 being measured respectively. The result shows that air pollution may increase occurrence and exacerbation of respiratory disease. Conclusion: High temperature and local climatic conditions in urban Nigeria encourages formation of Ozone, the major constituent of photochemical smog, resulting also in the formation of secondary air pollutants associated with health challenges. In this study we confirm the likely potency of the pattern of secondary air pollution in exacerbating COPD symptoms in vulnerable patient group in urban Nigeria. There is need for better regulation and measures to reduce ozone, particularly when local climatic conditions favour development of photochemical smog in such settings. Climate change and likely increasing temperatures add impetus and urgency for better air quality standards and measures (traffic-restrictions and emissions standards) in developing world settings such as Nigeria.

Keywords: Abuja-Nigeria, effect, photochemical smog, respiratory health

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Authors: John D. Sanderson

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The popularity of American cinema worldwide has contributed to the development of sociolects related to specific film genres in other cultural contexts by means of screen translation, in many cases eluding norms of usage in the target language, a process whose result has come to be known as 'dubbese'. A consequence for the reception in countries where local audiovisual fiction consumption is far lower than American imported productions is that this linguistic construct is preferred, even though it differs from common everyday speech. The iconography of film genres such as science-fiction, western or sword-and-sandal films, for instance, generates linguistic expectations in international audiences who will accept more easily the sociolects assimilated by the continuous reception of American productions, even if the themes, locations, characters, etc., portrayed on screen may belong in origin to other cultures. And the non-normative language (e.g., calques, semantic loans) used in the preferred mode of linguistic transfer, whether it is translation for dubbing or subtitling, has diachronically evolved in many cases into a status of canonized sociolect, not only accepted but also required, by foreign audiences of American films. However, a remarkable step forward is taken when this typology of artificial linguistic constructs starts being used creatively by nationals of these target cultural contexts. In the case of Spain, the success of American sitcoms such as Friends in the 1990s led Spanish television scriptwriters to include in national productions lexical and syntactical indirect borrowings (Anglicisms not formally identifiable as such because they include elements from their own language) in order to target audiences of the former. However, this commercial strategy had already taken place decades earlier when Spain became a favored location for the shooting of foreign films in the early 1960s. The international popularity of the then newly developed sub-genre known as Spaghetti-Western encouraged Spanish investors to produce their own movies, and local scriptwriters made use of the dubbese developed nationally since the advent of sound in film instead of using normative language. As a result, direct Anglicisms, as well as lexical and syntactical borrowings made up the creative writing of these Spanish productions, which also became commercially successful. Interestingly enough, some of these films were even marketed in English-speaking countries as original westerns (some of the names of actors and directors were anglified to that purpose) dubbed into English. The analysis of these 'back translations' will also foreground some semantic distortions that arose in the process. In order to perform the research on these issues, a wide corpus of American films has been used, which chronologically range from Stagecoach (John Ford, 1939) to Django Unchained (Quentin Tarantino, 2012), together with a shorter corpus of Spanish films produced during the golden age of Spaghetti Westerns, from una tumba para el sheriff (Mario Caiano; in English lone and angry man, William Hawkins) to tu fosa será la exacta, amigo (Juan Bosch, 1972; in English my horse, my gun, your widow, John Wood). The methodology of analysis and the conclusions reached could be applied to other genres and other cultural contexts.

Keywords: dubbing, film genre, screen translation, sociolect

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Authors: Chirag Raval, Jimmy Toussaint, Tieuvi Nguyen, Hadi Fadaifard, George Wolberg, Steven Quarfordt, Kung-ming Jan, David S. Rumschitzki

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Numerous studies examine aquaporins’ role in osmotic water transport in various systems but virtually none focus on aquaporins’ role in hydrostatically-driven water transport involving mammalian cells save for our laboratory’s recent study of aortic endothelial cells. Here we investigate aquaporin-1 expression and function in the aortic endothelium in two high-renin rat models of hypertension, the spontaneously hypertensive genomically altered Wystar-Kyoto rat variant and Sprague-Dawley rats made hypertensive by two kidney, one clip Goldblatt surgery. We measured aquaporin-1 expression in aortic endothelial cells from whole rat aortas by quantitative immunohistochemistry, and function by measuring the pressure driven hydraulic conductivities of excised rat aortas with both intact and denuded endothelia on the same vessel. We use them to calculate the effective intimal hydraulic conductivity, which is a combination of endothelial and subendothelial components. We observed well-correlated enhancements in aquaporin-1 expression and function in both hypertensive rat models as well as in aortas from normotensive rats whose expression was upregulated by 2h forskolin treatment. Upregulated aquaporin-1 expression and function may be a response to hypertension that critically determines conduit artery vessel wall viability and long-term susceptibility to atherosclerosis. Numerous studies examine aquaporins’ role in osmotic water transport in various systems but virtually none focus on aquaporins’ role in hydrostatically-driven water transport involving mammalian cells save for our laboratory’s recent study of aortic endothelial cells. Here we investigate aquaporin-1 expression and function in the aortic endothelium in two high-renin rat models of hypertension, the spontaneously hypertensive genomically altered Wystar-Kyoto rat variant and Sprague-Dawley rats made hypertensive by two kidney, one clip Goldblatt surgery. We measured aquaporin-1 expression in aortic endothelial cells from whole rat aortas by quantitative immunohistochemistry, and function by measuring the pressure driven hydraulic conductivities of excised rat aortas with both intact and denuded endothelia on the same vessel. We use them to calculate the effective intimal hydraulic conductivity, which is a combination of endothelial and subendothelial components. We observed well-correlated enhancements in aquaporin-1 expression and function in both hypertensive rat models as well as in aortas from normotensive rats whose expression was upregulated by 2h forskolin treatment. Upregulated aquaporin-1 expression and function may be a response to hypertension that critically determines conduit artery vessel wall viability and long-term susceptibility to atherosclerosis.

Keywords: acute hypertension, aquaporin-1, hydraulic conductivity, hydrostatic pressure, aortic endothelial cells, transcellular flow

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Authors: William Michael Short

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Semantic Web’ technologies such as the Unified Medical Language System Metathesaurus, SNOMED-CT, and MeSH have been touted as transformational for the way users access online medical and health information, enabling both the automated analysis of natural-language data and the integration of heterogeneous healthrelated resources distributed across the Internet through the use of standardized terminologies that capture concepts and relationships between concepts that are expressed differently across datasets. However, the approaches that have so far characterized ‘semantic bioinformatics’ have not yet fulfilled the promise of the Semantic Web for medical and health information retrieval applications. This paper argues within the perspective of cognitive linguistics and cognitive anthropology that four features of human meaning-making must be taken into account before the potential of semantic technologies can be realized for this domain. First, many semantic technologies operate exclusively at the level of the word. However, texts convey meanings in ways beyond lexical semantics. For example, transitivity patterns (distributions of active or passive voice) and modality patterns (configurations of modal constituents like may, might, could, would, should) convey experiential and epistemic meanings that are not captured by single words. Language users also naturally associate stretches of text with discrete meanings, so that whole sentences can be ascribed senses similar to the senses of words (so-called ‘discourse topics’). Second, natural language processing systems tend to operate according to the principle of ‘one token, one tag’. For instance, occurrences of the word sound must be disambiguated for part of speech: in context, is sound a noun or a verb or an adjective? In syntactic analysis, deterministic annotation methods may be acceptable. But because natural language utterances are typically characterized by polyvalency and ambiguities of all kinds (including intentional ambiguities), such methods leave the meanings of texts highly impoverished. Third, ontologies tend to be disconnected from everyday language use and so struggle in cases where single concepts are captured through complex lexicalizations that involve profile shifts or other embodied representations. More problematically, concept graphs tend to capture ‘expert’ technical models rather than ‘folk’ models of knowledge and so may not match users’ common-sense intuitions about the organization of concepts in prototypical structures rather than Aristotelian categories. Fourth, and finally, most ontologies do not recognize the pervasively figurative character of human language. However, since the time of Galen the widespread use of metaphor in the linguistic usage of both medical professionals and lay persons has been recognized. In particular, metaphor is a well-documented linguistic tool for communicating experiences of pain. Because semantic medical knowledge-bases are designed to help capture variations within technical vocabularies – rather than the kinds of conventionalized figurative semantics that practitioners as well as patients actually utilize in clinical description and diagnosis – they fail to capture this dimension of linguistic usage. The failure of semantic technologies in these respects degrades the efficiency and efficacy not only of medical research, where information retrieval inefficiencies can lead to direct financial costs to organizations, but also of care provision, especially in contexts of patients’ self-management of complex medical conditions.

Keywords: ambiguity, bioinformatics, language, meaning, metaphor, ontology, semantic web, semantics

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Authors: N. Rambabu, H. Gururaj, Reynold Washington, Oommen George

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Motivation: Under the USAID Strengthening Health Outcomes through Private Sector (SHOPS-TB) initiative, Karnataka Health Promotion Trust (KHPT) with technical support of Abt associates is implementing a TB prevention and care model in Karnataka State, South India. KHPT is the interface agency between the public and private sectors, and providers and the target community facilitating early TB case detection and enhancing treatment compliance through private health care providers (pHCP) engagement in RNTCP. The project coverage is 0.84 million urban poor from 663 slums in 12 districts of Karnataka. Problem Statement: India with the highest burden of global TB (26%) and two million cases annually, accounts for approximately one fifth of the global incidence. WHO estimates 300,000 people die from TB annually in India. India expanded the coverage of Directly Observed Treatment, Short-course chemotherapy (DOTS) to the entire country as early as 2006. However, the performance of RNTCP has not been uniform across states. While the national annual new smear-positive (NSP) case notification rate is 53, it is much lower at 47 in Karnataka. A third of TB patients in India reside in urban slums. Approach: Under SHOPS, KHPT actively engages with communities through key opinion leaders and community structures. Interpersonal communication, by Outreach workers through house-to-house visits and at aggregation points, is the primary method used for communication about TB and its management and to increase demand for sputum examination and DOTS. pHCP are mapped, trained and mentored by KHPT. ORWs also provide patient and family counseling on TB treatment, side effects and adherence, screen close contacts of index patients especially children under 6 years of age and screen co-morbidities including HIV, diabetes and malnutrition and risk factors including alcoholism, tobacco use, occupational hazards making appropriate accompanied or documented referrals. A treatment ‘buddy’ system for the patients involving close friends or family members, ICT-based support, DOTS Prerana (inspiration) groups of TB patients, family members and community, DOTS Mitra (friend) helpline services are also used for care and support services. Results: The intervention educated 39988 slum dwellers, referred 1731 chest symptomatics, tested 1061 patients and initiated 248 patients on anti-TB treatment within three months of intervention through continuous community engagement. Conclusions: The intervention’s potential to increase access to preferred health care providers, reduce patient and health system delays in diagnosis and initiation of treatment, improve health seeking behaviour and enhance compliance of pHCPs to standard treatment protocols is being monitored. Initial results are promising.

Keywords: DOTS, KHPT, health outcomes, public and private sector

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Authors: Jenson George, Thoa Nguyen, Garth Sanewski, Craig Hardner, Heather Eunice Smyth

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Pineapple (Ananas comosus), with its unique sweet flavour, is one of the most popular tropical, non-climacteric fruits consumed worldwide. It is also the third most important tropical fruit in world production. In Australia, 99% of the pineapple production is from the Queensland state due to the favourable subtropical climatic conditions. The flavourful fruit is known to contain around 500 volatile organic compounds (VOC) at varying concentrations and greatly contribute to the flavour quality of pineapple fruit by providing distinct aroma sensory properties that are sweet, fruity, tropical, pineapple-like, caramel-like, coconut-like, etc. The aroma of pineapple is one of the important factors attracting consumers and strengthening the marketplace. To better understand the aroma of Australian-grown pineapples, the matrix-matched Gas chromatography–mass spectrometry (GC-MS), Head Space - Solid-phase microextraction (HS-SPME), Stable-isotope dilution analysis (SIDA) method was developed and validated. The developed method represents a significant improvement over current methods with the incorporation of multiple external reference standards, multiple isotopes labeled internal standards, and a matching model system of pineapple fruit matrix. This method was employed to quantify 28 key aroma compounds in more than 200 genetically diverse pineapple varieties from a breeding program. The Australian pineapple cultivars varied in content and composition of free volatile compounds, which were predominantly comprised of esters, followed by terpenes, alcohols, aldehydes, and ketones. Using selected commercial cultivars grown in Australia, and by employing the sensorial analysis, the appearance (colour), aroma (intensity, sweet, vinegar/tang, tropical fruits, floral, coconut, green, metallic, vegetal, fresh, peppery, fermented, eggy/sulphurous) and texture (crunchiness, fibrousness, and juiciness) were obtained. Relationships between sensory descriptors and volatiles were explored by applying multivariate analysis (PCA) to the sensorial and chemical data. The key aroma compounds of pineapple exhibited a positive correlation with corresponding sensory properties. The sensory and volatile data were also used to explore genetic diversity in the breeding population. GWAS was employed to unravel the genetic control of the pineapple volatilome and its interplay with fruit sensory characteristics. This study enhances our understanding of pineapple aroma (flavour) compounds, their biosynthetic pathways and expands breeding option for pineapple cultivars. This research provides foundational knowledge to support breeding programs, post-harvest and target market studies, and efforts to optimise the flavour of commercial pineapple varieties and their parent lines to produce better tasting fruits for consumers.

Keywords: Ananas comosus, pineapple, flavour, volatile organic compounds, aroma, Gas chromatography–mass spectrometry (GC-MS), Head Space - Solid-phase microextraction (HS-SPME), Stable-isotope dilution analysis (SIDA).

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Authors: Brogan Guest, Amy Donaldson-Perrott

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The Master’s of Physician Associate Studies (MPAS) programme at St George’s, University of London (SGUL), is an intensive two-year course that trains students to become physician associates (PAs). PAs are generalized healthcare providers who work in primary and secondary care across the UK. PA programmes face the difficult task of preparing students to become safe medical providers in two short years. Our goal is to teach students to develop clinical reasoning early on in their studies and historically, this has been done predominantly though problem-based learning (PBL). We have had an increase concern about student engagement in PBL and difficulty recruiting facilitators to maintain the low student to facilitator ratio required in PBL. To address this issue, we created ‘Clinical Application of Anatomy and Physiology (CAAP)’. These peer-led, interactive, problem-based, small group sessions were designed to facilitate students’ clinical reasoning skills. The sessions were designed using the concept of Team-Based Learning (TBL). Students were divided into small groups and each completed a pre-session quiz consisting of difficult questions devised to assess students’ application of medical knowledge. The quiz was completed in small groups and they were not permitted access of external resources. After the quiz, students worked through a series of openended, clinical tasks using all available resources. They worked at their own pace and the session was peer-led, rather than facilitator-driven. For a group of 35 students, there were two facilitators who observed the sessions. The sessions utilised an infinite space whiteboard software. Each group member was encouraged to actively participate and work together to complete the 15-20 tasks. The session ran for 2 hours and concluded with a post-session quiz, identical to the pre-session quiz. We obtained subjective feedback from students on their experience with CAAP and evaluated the objective benefit of the sessions through the quiz results. Qualitative feedback from students was generally positive with students feeling the sessions increased engagement, clinical understanding, and confidence. They found the small group aspect beneficial and the technology easy to use and intuitive. They also liked the benefit of building a resource for their future revision, something unique to CAAP compared to PBL, which out students participate in weekly. Preliminary quiz results showed improvement from pre- and post- session; however, further statistical analysis will occur once all sessions are complete (final session to run December 2022) to determine significance. As a post-graduate healthcare professional programme, we have a strong focus on self-directed learning. Whilst PBL has been a mainstay in our curriculum since its inception, there are limitations and concerns about its future in view of student engagement and facilitator availability. Whilst CAAP is not TBL, it draws on the benefits of peer-led, small group work with pre- and post- team-based quizzes. The pilot of these sessions has shown that students are engaged by CAAP, and they can make significant progress in clinical reasoning in a short amount of time. This can be achieved with a high student to facilitator ratio.

Keywords: problem based learning, team based learning, active learning, peer-to-peer teaching, engagement

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Authors: Luminiţa Duţică, Gheorghe Duţică

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One of the most powerful language innovation in the twentieth century music was the heterophony–hypostasis of the vertical syntax entered into the sphere of interest of many composers, such as George Enescu, Pierre Boulez, Mauricio Kagel, György Ligeti and others. The heterophonic syntax has a history of its growth, which means a succession of different concepts and writing techniques. The trajectory of settling this phenomenon does not necessarily take into account the chronology: there are highly complex primary stages and advanced stages of returning to the simple forms of writing. In folklore, the plurimelodic simultaneities are free or random and originate from the (unintentional) differences/‘deviations’ from the state of unison, through a variety of ornaments, melismas, imitations, elongations and abbreviations, all in a flexible rhythmic and non-periodic/immeasurable framework, proper to the parlando-rubato rhythmics. Within the general framework of the multivocal organization, the heterophonic syntax in elaborate (academic) version has imposed itself relatively late compared with polyphony and homophony. Of course, the explanation is simple, if we consider the causal relationship between the sound vocabulary elements – in this case, the modalism – and the typologies of vertical organization appropriate for it. Therefore, adding up the ‘classic’ pathway of the writing typologies (monody – polyphony – homophony), heterophony - applied equally to the structures of modal, serial or synthesis vocabulary – reclaims necessarily an own macrotemporal form, in the sense of the analogies enshrined by the evolution of the musical styles and languages: polyphony→fugue, homophony→sonata. Concerned about the prospect of edifying a new musical ontology, the composer Ştefan Niculescu experienced – along with the mathematical organization of heterophony according to his own original methods – the possibility of extrapolation of this phenomenon in macrostructural plan, reaching this way to the unique form of ‘synchrony’. Founded on coincidentia oppositorum principle (involving the ‘one-multiple’ binom), the sound architecture imagined by Ştefan Niculescu consists in one (temporal) model / algorithm of articulation of two sound states: 1. monovocality state (principle of identity) and 2. multivocality state (principle of difference). In this context, the heterophony becomes an (auto)generative mechanism, with macrotemporal amplitude, strategy that will be grown by the composer, practically throughout his creation (see the works: Ison I, Ison II, Unisonos I, Unisonos II, Duplum, Triplum, Psalmus, Héterophonies pour Montreux (Homages to Enescu and Bartók etc.). For the present demonstration, we selected one of the most edifying works of Ştefan Niculescu – Simphony II, Opus dacicum – where the form of (heterophony-)synchrony acquires monumental-symphonic features, representing an emblematic case for the complexity level achieved by this type of vertical syntax in the twentieth century music.

Keywords: heterophony, modalism, serialism, synchrony, syntax

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Authors: Sini George

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Active learning pedagogies are valued for their success in increasing 21st-century learners’ engagement, developing transferable skills like critical thinking or quantitative reasoning, and creating deeper and more lasting educational gains. 'Blended learning' is an active learning pedagogical approach in which direct instruction moves from the group learning space to the individual learning space, and the resulting group space is transformed into a dynamic, interactive learning environment where the educator guides students as they apply concepts and engage creatively in the subject matter. This project aimed to develop a blended learning instructional approach to teaching concepts around pharmaceutical calculations to year 1 pharmacy students. The wrong dose, strength or frequency of a medication accounts for almost a third of medication errors in the NHS therefore, progression to year 2 requires a 70% pass in this calculation test, in addition to the standard progression requirements. Many students were struggling to achieve this requirement in the past. It was also challenging to teach these concepts to students of a large class (> 130) with mixed mathematical abilities, especially within a traditional didactic lecture format. Therefore, short screencasts with voice-over of the lecturer were provided in advance of a total of four teaching sessions (two hours/session), incorporating core content of each session and talking through how they approached the calculations to model metacognition. Links to the screencasts were posted on the learning management. Viewership counts were used to determine that the students were indeed accessing and watching the screencasts on schedule. In the classroom, students had to apply the knowledge learned beforehand to a series of increasingly difficult set of questions. Students were then asked to create a question in group settings (two students/group) and to discuss the questions created by their peers in their groups to promote deep conceptual learning. Students were also given time for question-and-answer period to seek clarifications on the concepts covered. Student response to this instructional approach and their test grades were collected. After collecting and organizing the data, statistical analysis was carried out to calculate binomial statistics for the two data sets: the test grade for students who received blended learning instruction and the test grades for students who received instruction in a standard lecture format in class, to compare the effectiveness of each type of instruction. Student response and their performance data on the assessment indicate that the learning of content in the blended learning instructional approach led to higher levels of student engagement, satisfaction, and more substantial learning gains. The blended learning approach enabled each student to learn how to do calculations at their own pace freeing class time for interactive application of this knowledge. Although time-consuming for an instructor to implement, the findings of this research demonstrate that the blended learning instructional approach improves student academic outcomes and represents a valuable method to incorporate active learning methodologies while still maintaining broad content coverage. Satisfaction with this approach was high, and we are currently developing more pharmacy content for delivery in this format.

Keywords: active learning, blended learning, deep conceptual learning, instructional approach, metacognition, pharmaceutical calculations

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Authors: Natalie Riley, Anita Quigley, Robert M. I. Kapsa, George W. Greene

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As the fields of medicine and bionics grow rapidly in technological advancement, the future and success of it depends on the ability to effectively interface between the artificial and the biological worlds. The biggest obstacle when it comes to implantable, electronic medical devices, is maintaining a ‘clean’, low noise electrical connection that allows for efficient sharing of electrical information between the artificial and biological systems. Implant fouling occurs with the adhesion and accumulation of proteins and various cell types as a result of the immune response to protect itself from the foreign object, essentially forming an electrical insulation barrier that often leads to implant failure over time. Lubricin (LUB) functions as a major boundary lubricant in articular joints, a unique glycoprotein with impressive anti-adhesive properties that self-assembles to virtually any substrate to form a highly ordered, ‘telechelic’ polymer brush. LUB does not passivate electroactive surfaces which makes it ideal, along with its innate biocompatibility, as a coating for implantable bionic electrodes. It is the aim of the study to investigate LUB’s anti-fouling properties and its potential as a safe, bioinspired material for coating applications to enhance the performance and longevity of implantable medical devices as well as reducing the frequency of implant replacement surgeries. Native, bovine-derived LUB (N-LUB) and recombinant LUB (R-LUB) were applied to gold-coated mylar surfaces. Fibroblast, chondrocyte and neural cell types were cultured and grown on the coatings under both passive and electrically stimulated conditions to test the stability and anti-adhesive property of the LUB coating in the presence of an electric field. Lactate dehydrogenase (LDH) assays were conducted as a directly proportional cell population count on each surface along with immunofluorescent microscopy to visualize cells. One-way analysis of variance (ANOVA) with post-hoc Tukey’s test was used to test for statistical significance. Under both passive and electrically stimulated conditions, LUB significantly reduced cell attachment compared to bare gold. Comparing the two coating types, R-LUB reduced cell attachment significantly compared to its native counterpart. Immunofluorescent micrographs visually confirmed LUB’s antiadhesive property, R-LUB consistently demonstrating significantly less attached cells for both fibroblasts and chondrocytes. Preliminary results investigating neural cells have so far demonstrated that R-LUB has little effect on reducing neural cell attachment; the study is ongoing. Recombinant LUB coatings demonstrated impressive anti-adhesive properties, reducing cell attachment in fibroblasts and chondrocytes. These findings and the availability of recombinant LUB brings into question the results of previous experiments conducted using native-derived LUB, its potential not adequately represented nor realized due to unknown factors and impurities that warrant further study. R-LUB is stable and maintains its anti-fouling property under electrical stimulation, making it suitable for electroactive surfaces.

Keywords: anti-fouling, bioinspired, cell attachment, lubricin

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Authors: Michelle E. Taylor, Clare E. Morrall

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Microplastics are small particles produced for industrial purposes or formed by breakdown of anthropogenic debris. Caribbean nations import large quantities of plastic products. The Caribbean region is vulnerable to natural disasters and Climate Change is predicted to bring multiple additional challenges to island nations. Microplastics have been found in an array of marine environments and in a diversity of marine species. Occurrence of microplastic in the intestinal tracts of marine fish is a concern to human and ecosystem health as pollutants and pathogens can associate with plastics. Studies have shown that the incidence of microplastics in marine fish varies with species and location. Prevalence of microplastics (≤ 5 mm) in fish species from Grenadian waters (representing pelagic, semi-pelagic and demersal lifestyles) harvested for human consumption have been investigated via gut analysis. Harvested tissue was digested in 10% KOH and particles retained on a 0.177 mm sieve were examined. Microplastics identified have been classified according to type, colour and size. Over 97% of fish examined thus far (n=34) contained microplastics. Current and future work includes examining the invasive Lionfish (Pterois spp.) for microplastics, investigating marine invertebrate species as well as examining environmental sources of microplastics (i.e. rivers, coastal waters and sand). Owing to concerns of pollutant accumulation on microplastics and potential migration into organismal tissues, we plan to analyse fish tissue for mercury and other persistent pollutants. Despite having ~110,000 inhabitants, the island nation of Grenada imported approximately 33 million plastic bottles in 2013, of which it is estimated less than 5% were recycled. Over 30% of the imported bottles were ‘unmanaged’, and as such are potential litter/marine debris. A revised Litter Abatement Act passed into law in Grenada in 2015, but little enforcement of the law is evident to date. A local Non-governmental organization (NGO) ‘The Grenada Green Group’ (G3) is focused on reducing litter in Grenada through lobbying government to implement the revised act and running sessions in schools, community groups and on local media and social media to raise awareness of the problems associated with plastics. A local private company has indicated willingness to support an Anti-Litter Campaign in 2018 and local awareness of the need for a reduction of single use plastic use and litter seems to be high. The Government of Grenada have called for a Sustainable Waste Management Strategy and a ban on both Styrofoam and plastic grocery bags are among recommendations recently submitted. A Styrofoam ban will be in place at the St. George’s University campus from January 1st, 2018 and many local businesses have already voluntarily moved away from Styrofoam. Our findings underscore the importance of continuing investigations into microplastics in marine life; this will contribute to understanding the associated health risks. Furthermore, our findings support action to mitigate the volume of plastics entering the world’s oceans. We hope that Grenada’s future will involve a lot less plastic. This research was supported by the Caribbean Node of the Global Partnership on Marine Litter.

Keywords: Caribbean, microplastics, pollution, small island developing nation

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Authors: Swati Gautam, Salman Akhtar, S. P. Jaiswar, Amita Jain

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Background: FGTB is now a major global health problem mostly in developing countries including India. In humans, Mycobacterium Tuberculosis (M.tb) is a causating agent of infection. High index of suspicion is required for early diagnosis due to asymptomatic presentation of FGTB disease. In macrophages Toll Like Receptor-2 (TLR-2) is one which mediated host’s immune response to M.tb. The expression of TLR-2 on macrophages is important to determine the fate of innate immune responses to M.tb. TLR-2 have two work. First its high expression on macrophages worsen the outer of infection and another side, it maintains M.tb to its dormant stage avoids activation of M.tb from latent phase. Single Nucleotide Polymorphism (SNP) of TLR-2 gene plays an important role in susceptibility to TB among different populations and subsequently, in the development of infertility. Methodology: This Case-Control study was done in the Department of Obs and Gynae and Department of Microbiology at King George’s Medical University, U.P, Lucknow, India. Total 300 subjects (150 Cases and 150 Controls) were enrolled in the study. All subjects were enrolled only after fulfilling the given inclusion and exclusion criteria. Inclusion criteria: Age 20-35 years, menstrual-irregularities, positive on Acid-Fast Bacilli (AFB), TB-PCR, (LJ/MGIT) culture in Endometrial Aspiration (EA). Exclusion criteria: Koch’s active, on ATT, PCOS, and Endometriosis fibroid women, positive on Gonococal and Chlamydia. Blood samples were collected in EDTA tubes from cases and healthy control women (HCW) and genomic DNA extraction was carried out by salting-out method. Genotyping of TLR2 genetic variants (Arg753Gln and Arg677Trp) were performed by using single amplification refractory mutation system (ARMS) PCR technique. PCR products were analyzed by electrophoresis on 1.2% agarose gel and visualized by gel-doc. Statistical analysis of the data was performed using the SPSS 16.3 software and computing odds ratio (OR) with 95% CI. Linkage Disequiliribium (LD) analysis was done by SNP stats online software. Results: In TLR-2 (Arg753Gln) polymorphism significant risk of FGTB observed with GG homozygous mutant genotype (OR=13, CI=0.71-237.7, p=0.05), AG heterozygous mutant genotype (OR=13.7, CI=0.76-248.06, p=0.03) however, G allele (OR=1.09, CI=0.78-1.52, p=0.67) individually was not associated with FGTB. In TLR-2 (Arg677Trp) polymorphism a significant risk of FGTB observed with TT homozygous mutant genotype (OR= 0.020, CI=0.001-0.341, p < 0.001), CT heterozygous mutant genotype (OR=0.53, CI=0.33-0.86, p=0.014) and T allele (OR=0.463, CI=0.32-0.66, p < 0.001). TT mutant genotype was only found in FGTB cases and frequency of CT heterozygous more in control group as compared to FGTB group. So, CT genotype worked as protective mutation for FGTB susceptibility group. In haplotype analysis of TLR-2 genetic variants, four possible combinations, i.e. (G-T, A-C, G-C, and A-T) were obtained. The frequency of haplotype A-C was significantly higher in FGTB cases (0.32). Control group did not show A-C haplotype and only found in FGTB cases. Conclusion: In conclusion, study showed a significant association with both genetic variants of TLR-2 of FGTB disease. Moreover, the presence of specific associated genotype/alleles suggest the possibility of disease severity and clinical approach aimed to prevent extensive damage by disease and also helpful for early detection of disease.

Keywords: ARMS, EDTA, FGTB, TLR

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Authors: Mian Huang, Chi Ma, Junyu Lin, William Lu

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Introduction: Bone health attracts more attention recently and an intelligent question and answer (QA) chatbot for osteoporosis is helpful for science popularization. With Generative Pretrained Transformer (GPT) technology developing, we build an osteoporosis corpus dataset and then fine-tune LLaMA, a famous open-source GPT foundation large language model(LLM), on our self-constructed osteoporosis corpus. Evaluated by clinical orthopedic experts, our fine-tuned model outperforms vanilla LLaMA on osteoporosis QA task in Chinese. Three-dimensional quantitative computed tomography (QCT) measured bone mineral density (BMD) is considered as more accurate than DXA for BMD measurement in recent years. We develop an automatic Phantom-less QCT(PL-QCT) that is more efficient for BMD measurement since no need of an external phantom for calibration. Combined with LLM on osteoporosis, our PL-QCT provides efficient and accurate BMD measurement for our chatbot users. Material and Methods: We build an osteoporosis corpus containing about 30,000 Chinese literatures whose titles are related to osteoporosis. The whole process is done automatically, including crawling literatures in .pdf format, localizing text/figure/table region by layout segmentation algorithm and recognizing text by OCR algorithm. We train our model by continuous pre-training with Low-rank Adaptation (LoRA, rank=10) technology to adapt LLaMA-7B model to osteoporosis domain, whose basic principle is to mask the next word in the text and make the model predict that word. The loss function is defined as cross-entropy between the predicted and ground-truth word. Experiment is implemented on single NVIDIA A800 GPU for 15 days. Our automatic PL-QCT BMD measurement adopt AI-associated region-of-interest (ROI) generation algorithm for localizing vertebrae-parallel cylinder in cancellous bone. Due to no phantom for BMD calibration, we calculate ROI BMD by CT-BMD of personal muscle and fat. Results & Discussion: Clinical orthopaedic experts are invited to design 5 osteoporosis questions in Chinese, evaluating performance of vanilla LLaMA and our fine-tuned model. Our model outperforms LLaMA on over 80% of these questions, understanding ‘Expert Consensus on Osteoporosis’, ‘QCT for osteoporosis diagnosis’ and ‘Effect of age on osteoporosis’. Detailed results are shown in appendix. Future work may be done by training a larger LLM on the whole orthopaedics with more high-quality domain data, or a multi-modal GPT combining and understanding X-ray and medical text for orthopaedic computer-aided-diagnosis. However, GPT model gives unexpected outputs sometimes, such as repetitive text or seemingly normal but wrong answer (called ‘hallucination’). Even though GPT give correct answers, it cannot be considered as valid clinical diagnoses instead of clinical doctors. The PL-QCT BMD system provided by Bone’s QCT(Bone’s Technology(Shenzhen) Limited) achieves 0.1448mg/cm2(spine) and 0.0002 mg/cm2(hip) mean absolute error(MAE) and linear correlation coefficient R2=0.9970(spine) and R2=0.9991(hip)(compared to QCT-Pro(Mindways)) on 155 patients in three-center clinical trial in Guangzhou, China. Conclusion: This study builds a Chinese osteoporosis corpus and develops a fine-tuned and domain-adapted LLM as well as a PL-QCT BMD measurement system. Our fine-tuned GPT model shows better capability than LLaMA model on most testing questions on osteoporosis. Combined with our PL-QCT BMD system, we are looking forward to providing science popularization and early morning screening for potential osteoporotic patients.

Keywords: GPT, phantom-less QCT, large language model, osteoporosis

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Authors: Kyriaki Hatziagapiou, Konstantinos Bethanis, Olti Nikola, Elias Christoforides, Eleni Koniari, Eleni Kakouri, George Lambrou, Christina Kanaka-Gantenbein

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Glioblastoma multiforme (GBM) remains a serious health challenge, as current therapeutic modalities continue to yield unsatisfactory results, with the average survival rarely exceeding 1-2 years. Natural compounds still provide some of the most promising approaches for discovering new drugs. The non-psychotropic cannabidiol (CBD) deriving from Cannabis sativa L. provides such promise. CBD is endowed with anticancer, antioxidant, and genoprotective properties as established in vitro and in in vivo experiments. CBD’s selectivity towards cancer cells and its safe profile suggest its usage in cancer therapies. However, the bioavailability of oral CBD is low due to poor aqueous solubility, erratic gastrointestinal absorption, and significant first-pass metabolism, hampering its therapeutic potential and resulting in a variable pharmacokinetic profile. In this context, CBD can take great advantage of nanomedicine-based formulation strategies. Cyclodextrins (CDs) are cyclic oligosaccharides used in the pharmaceutical industry to incorporate apolar molecules inside their hydrophobic cavity, increasing their stability, water solubility, and bioavailability or decreasing their side effects. CBD-inclusion complexes with CDs could be a good strategy to improve its properties, like solubility and stability to harness its full therapeutic potential. The current research aims to study the potential cytotoxic effect of CBD and CBD-CDs complexes CBD-RMβCD (randomly methylated β-cyclodextrin) and CBD-HPβCD (hydroxypropyl-b-CD) on the A172 glioblastoma cell line. CBD is diluted in 10% DMSO, and CBD/CDs solutions are prepared by mixing solid CBD, solid CDs, and dH2O. For the biological assays, A172 cells are incubated at a range of concentrations of CBD, CBD-RMβCD and CBD-HPβCD, RMβCD, and HPβCD (0,03125-4 mg/ml) at 24, 48, and 72 hours. Analysis of cell viability after incubation with the compounds is performed with Alamar Blue viability assay. CBD’s dilution to DMSO 10% was inadequate, as crystals are observed; thus cytotoxicity experiments are not assessed. CBD’s solubility is enhanced in the presence of both CDs. CBD/CDs exert significant cytotoxicity in a dose and time-dependent manner (p < 0.005 for exposed cells to any concentration at 48, 72, and 96 hours versus cells not exposed); as their concentration and time of exposure increases, the reduction of resazurin to resofurin decreases, indicating a reduction in cell viability. The cytotoxic effect is more pronounced in cells exposed to CBD-HPβCD for all concentrations and time-points. RMβCD and HPβCD at the highest concentration of 4 mg/ml also exerted antitumor action per se since manifesting cell growth inhibition. The results of our study could afford the basis of research regarding the use of natural products and their inclusion complexes as anticancer agents and the shift to targeted therapy with higher efficacy and limited toxicity. Acknowledgments: The research is partly funded by ΙΚΥ (State Scholarships Foundation) – Post-doc Scholarships-Partnership Agreement 2014-2020.

Keywords: cannabidiol, cyclodextrins, glioblastoma, hydroxypropyl-b-Cyclodextrin, randomly-methylated-β-cyclodextrin

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Authors: James Brown, Stella Kortekaas, Ian Finnie, George Zhang, Christine Devine, Neil Healy

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The use of GIS as an analysis tool for engineering decision making is now best practice in the offshore industry. GIS enables multidisciplinary data integration, analysis and visualisation which allows the presentation of large and intricate datasets in a simple map-interface accessible to all project stakeholders. Presenting integrated geoscience and geotechnical data in GIS enables decision makers to be well-informed. This paper is a successful case study of how GIS spatial analysis techniques were applied to help select the most favourable pipeline route. Routing a pipeline through any natural environment has numerous obstacles, whether they be topographical, geological, engineering or financial. Where the pipeline is subjected to external hydrostatic water pressure and is carrying pressurised hydrocarbons, the requirement to safely route the pipeline through hazardous terrain becomes absolutely paramount. This study illustrates how the application of modern, GIS-based pipeline routing techniques enabled the identification of a single most-favourable pipeline route crossing of a challenging seabed terrain. Conventional approaches to pipeline route determination focus on manual avoidance of primary constraints whilst endeavouring to minimise route length. Such an approach is qualitative, subjective and is liable to bias towards the discipline and expertise that is involved in the routing process. For very short routes traversing benign seabed topography in shallow water this approach may be sufficient, but for deepwater geohazardous sites, the need for an automated, multi-criteria, and quantitative approach is essential. This study combined multiple routing constraints using modern least-cost-routing algorithms deployed in GIS, hitherto unachievable with conventional approaches. The least-cost-routing procedure begins with the assignment of geocost across the study area. Geocost is defined as a numerical penalty score representing hazard posed by each routing constraint (e.g. slope angle, rugosity, vulnerability to debris flows) to the pipeline. All geocosted routing constraints are combined to generate a composite geocost map that is used to compute the least geocost route between two defined terminals. The analyses were applied to select the most favourable pipeline route for a potential gas development in deep water. The study area is geologically complex with a series of incised, potentially active, canyons carved into a steep escarpment, with evidence of extensive debris flows. A similar debris flow in the future could cause significant damage to a poorly-placed pipeline. Protruding inter-canyon spurs offer lower-gradient options for ascending an escarpment but the vulnerability of periodic failure of these spurs is not well understood. Close collaboration between geoscientists, pipeline engineers, geotechnical engineers and of course the gas export pipeline operator guided the analyses and assignment of geocosts. Shorter route length, less severe slope angles, and geohazard avoidance were the primary drivers in identifying the most favourable route.

Keywords: geocost, geohazard, pipeline route determination, pipeline route optimisation, spatial analysis

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Authors: George Kyriakopoulos, Photini Pazartzis, Anthi Koskina, Crystalie Bourcha

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The need for securing safe access to and return from outer space, as well as ensuring the viability of outer space operations, maintains vivid the debate over the promotion of organization of space traffic through a Space Traffic Management System (STM). The proliferation of outer space activities in recent years as well as the dynamic emergence of the private sector has gradually resulted in a diverse universe of actors operating in outer space. The said developments created an increased adverse impact on outer space sustainability as the case of the growing number of space debris clearly demonstrates. The above landscape sustains considerable threats to outer space environment and its operators that need to be addressed by a combination of scientific-technological measures and regulatory interventions. In this context, recourse to recent technological advancements and, in particular, to Artificial Intelligence (AI) and machine learning systems, could achieve exponential results in promoting space traffic management with respect to collision avoidance as well as launch and re-entry procedures/phases. New technologies can support the prospects of a successful space traffic management system at an international scale by enabling, inter alia, timely, accurate and analytical processing of large data sets and rapid decision-making, more precise space debris identification and tracking and overall minimization of collision risks and reduction of operational costs. What is more, a significant part of space activities (i.e. launch and/or re-entry phase) takes place in airspace rather than in outer space, hence the overall discussion also involves the highly developed, both technically and legally, international (and national) Air Traffic Management System (ATM). Nonetheless, from a regulatory perspective, the use of AI for the purposes of space traffic management puts forward implications that merit particular attention. Key issues in this regard include the delimitation of AI-based activities as space activities, the designation of the applicable legal regime (international space or air law, national law), the assessment of the nature and extent of international legal obligations regarding space traffic coordination, as well as the appropriate liability regime applicable to AI-based technologies when operating for space traffic coordination, taking into particular consideration the dense regulatory developments at EU level. In addition, the prospects of institutionalizing international cooperation and promoting an international governance system, together with the challenges of establishment of a comprehensive international STM regime are revisited in the light of intervention of AI technologies. This paper aims at examining regulatory implications advanced by the use of AI technology in the context of space traffic management operations and its key correlating concepts (SSA, space debris mitigation) drawing in particular on international and regional considerations in the field of STM (e.g. UNCOPUOS, International Academy of Astronautics, European Space Agency, among other actors), the promising advancements of the EU approach to AI regulation and, last but not least, national approaches regarding the use of AI in the context of space traffic management, in toto. Acknowledgment: The present work was co-funded by the European Union and Greek national funds through the Operational Program "Human Resources Development, Education and Lifelong Learning " (NSRF 2014-2020), under the call "Supporting Researchers with an Emphasis on Young Researchers – Cycle B" (MIS: 5048145).

Keywords: artificial intelligence, space traffic management, space situational awareness, space debris

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Authors: Joshua Doe, George Amoako

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Purpose: In an increasingly digital world, the realm of sports fandom has extended its borders, creating a vibrant ecosystem of online communities centered around football clubs. This study ventures into the intricate interplay of motivations that drive football fans to respond to brand activism and its profound implications for brand antagonism and engagement among two of Ghana's most revered premier football clubs. Methods: A sample of 459 fervent fans from these two rival clubs were engaged through self-administered questionnaires expertly distributed via social media and online platforms. Data was analysed, using PLS-SEM. Findings: The tapestry of motivations that weave through these online football communities is as diverse as the fans themselves. It becomes apparent that fans are propelled by a spectrum of incentives. They seek education, yearn for information, revel in entertainment, embrace socialization, and fortify their self-esteem through their interactions within these digital spaces. Yet, it is the nuanced distinction in these motivations that shapes the trajectory of brand antagonism and engagement. Surprisingly, the study reveals a remarkable pattern. Football fans, despite their fierce rivalries, do not engage in brand antagonism based on educational pursuits, information-seeking endeavors, or socialization. Instead, it is motivations rooted in entertainment and self-esteem that serve as the fertile grounds for brand antagonism. Paradoxically, it is these very motivations coupled with the desire for socialization that nurture brand engagement, manifesting as active support and advocacy for their chosen club brand. Originality: Our research charters new waters by extending the boundaries of existing theories in the field. The Technology Acceptance Uses and Gratifications Theory, and Social Identity Theory all find new dimensions within the context of online brand community engagement. This not only deepens our understanding of the multifaceted world of online football fandom but also invites us to explore the implications these insights carry within the digital realm. Contribution to Practice: For marketers, our findings offer a treasure trove of actionable insights. They beckon the development of targeted content strategies that resonate with fan motivations. The implementation of brand advocacy programs, fostering opportunities for socialization, and the effective management of brand antagonism emerge as pivotal strategies. Furthermore, the utilization of data-driven insights is poised to refine consumer engagement strategies and strengthen brand affinity. Future Studies: For future studies, we advocate for longitudinal, cross-cultural, and qualitative studies that could shed further light on this topic. Comparative analyses across different types of online brand communities, an exploration of the role of brand community leaders, and inquiries into the factors that contribute to brand community dissolution all beckon the research community. Furthermore, understanding motivation-specific antagonistic behaviors and the intricate relationship between information-seeking and engagement present exciting avenues for further exploration. This study unfurls a vibrant tapestry of fan motivations, brand activism, and rivalry within online football communities. It extends a hand to scholars and marketers alike, inviting them to embark on a journey through this captivating digital realm, where passion, rivalry, and engagement harmonize to shape the world of sports fandom as we know it.

Keywords: online brand engagement, football fans, brand antagonism, motivations

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Authors: Anupama A. P.

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The Malayalam film industry, known as Mollywood, has a rich tradition of storytelling and cultural significance within Indian cinema. Middlebrow films have emerged as a distinct influential category, particularly in the 1980s, with directors like K.G. George, who engaged with female subjectivity and drew inspiration from the ‘women’s cinema’ of the 1950s and 1960s. In recent decades, particularly post-2010, the industry has transformed significantly with a new generation of filmmakers diverging from melodrama and new wave of the past, incorporating advanced technology and modern content. This study examines the evolution and impact of Malayalam middlebrow cinema in the 21st century, focusing on post-2000 films and their influence on contemporary spectator experiences. These films appeal to a wide range of audiences without compromising on their artistic integrity, tackling social issues and personal dramas with thematic and narrative complexity. Historically, middlebrow films in Malayalam cinema have portrayed realism and addressed the socio-political climate of Kerala, blending realism with reflexivity and moving away from traditional sentimentality. This shift is evident in the new generation of Malayalam films, which present a global representation of characters and a modern treatment of individuals. To provide a comprehensive understanding of this evolution, the study analyzes a diverse selection of films such as Kerala Varma Pazhassi Raja (2009), Drishyam (2013), Maheshinte Prathikaaram (2016), Take Off (2017), and Thondimuthalum Driksakshiyum (2017) and Virus (2019) illustrating the broad thematic range and innovative narrative techniques characteristic of this genre. These films exemplify how middlebrow cinema continues to evolve, adapting to changing societal contexts and audience expectations. This research employs a theoretical methodology, drawing on cultural studies and audience reception theory, utilizing frameworks such as Bordwell’s narrative theory, Deleuze’s concept of deterritorialization, and Hall’s encoding/decoding model to analyze the changes in Malayalam middlebrow cinema and interpret the storytelling methods, spectator experience, and audience reception of these films. The findings indicate that Malayalam middlebrow cinema post-2010 offers a spectator experience that is both intellectually stimulating and broadly appealing. This study highlights the critical role of middlebrow cinema in reflecting and shaping societal values, making it a significant cultural artefact within the broader context of Indian and global cinema. By bridging entertainment with thought-provoking narratives, these films engage audiences and contribute to wider cultural discourse, making them pivotal in contemporary cinematic landscapes. To conclude, this study highlights the importance of Malayalam middle-brow cinema in influencing contemporary cinematic tastes. The nuanced and approachable narratives of post-2010 films are posited to assume an increasingly pivotal role in the future of Malayalam cinema. By providing a deeper understanding of Malayalam middlebrow cinema and its societal implications, this study enriches theoretical discourse, promotes regional cinema, and offers valuable insights into contemporary spectator experiences and the future trajectory of Malayalam cinema.

Keywords: Malayalam cinema, middlebrow cinema, spectator experience, audience reception, deterritorialization

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Authors: Aisling Gough, Ruth F. Hunter, Jianjun Tang, Sarah F. Brennan, Oliver Smith, Mark A. Tully, Chris Patterson, Alberto Longo, George Hutchinson, Lindsay Prior, David French, Jean Adams, Emma McIntosh, Frank Kee

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Background: As a large proportion of the UK workforce is employed in sedentary occupations, worksite interventions have the potential to contribute significantly to the health of the population. The UK Government is currently encouraging the use of financial incentives to promote healthier lifestyles but there is a dearth of evidence regarding the effectiveness and sustainability of incentive schemes to promote physical activity in the workplace. Methods: A large cluster RCT is currently underway, incorporating nested behavioural economic field experiments and process evaluation, to evaluate the effectiveness of a Physical Activity Loyalty Scheme. Office-based employees were recruited from large public sector organisations in Lisburn and Belfast (Northern Ireland) and randomised to an Intervention or Control group. Participants in the Intervention Group were encouraged to take part in 150 minutes of physical activity per week through provision of financial incentives (retailer vouchers) to those who met physical activity targets throughout the course of the 6 month intervention. Minutes of physical activity were monitored when participants passed by sensors (holding a keyfob) placed along main walking routes, parks and public transport stops nearby their workplace. Participants in the Control Group will complete the same outcome assessments (waiting-list control). The primary outcome is steps per day measured via pedometers (7 days). Secondary outcomes include health and wellbeing (Short Form-8, EuroQol-5D-5L, Warwick Edinburgh Mental Well Being Scale), and work absenteeism and presenteeism. Data will be collected at baseline, 6, 12 and 18 months. Information on PAL card & website usage, voucher downloads and redemption of vouchers will also be collected as part of a comprehensive process evaluation. Results: In total, 853 participants have been recruited from 9 workplaces in Lisburn, 12 buildings within the Stormont Estate, Queen’s University Belfast and Belfast City Hospital. Participants have been randomised to intervention and control groups. Baseline and 6-month data for the Physical Activity Loyalty Scheme has been collected. Findings regarding the effectiveness of the intervention from the 6-month follow-up data will be presented. Discussion: This study will address the gap in knowledge regarding the effectiveness and cost-effectiveness of a workplace-based financial incentive scheme to promote a healthier lifestyle. As the UK workforce is increasingly sedentary, workplace-based physical activity interventions have significant potential in terms of encouraging employees to partake in physical activity during the working day which could lead to substantial improvements in physical activity levels overall. Implications: If a workplace based physical activity intervention such as this proves to be both effective and cost-effective, there is great potential to contribute significantly to the health and wellbeing of the workforce in the future. Workplace-based physical activity interventions have the potential to improve the physical and mental health of employees which may in turn lead to economic benefits for the employer, such as reduction in rates of absenteeism and increased productivity.

Keywords: behaviour change, cluster randomised controlled trial, loyalty scheme, physical activity

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Authors: Salam N. Abdo, Orien L. Tulp, George P. Einstein

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The purpose of this exploratory study was to gather the insights into psoriasis etiology, treatment, and patient experience, for developing psoriasis and psoriatic arthritis diagnostic test. Data collection methods consisted of a comprehensive meta-analysis of relevant studies and psoriasis patient survey. Established meta-analysis guidelines were used for the selection and qualitative comparative analysis of psoriasis and psoriatic arthritis research studies. Only studies that clearly discussed psoriasis etiology, treatment, and patient experience were reviewed and analyzed, to establish a qualitative data base for the study. Using the insights gained from meta-analysis, an existing psoriasis patient survey was modified and administered to collect additional data as well as triangulate the results. The hypothesis is that specific types of psoriatic disease have specific etiology and pathophysiologic pattern. The following etiology categories were identified: bacterial, environmental/microbial, genetic, immune, infectious, trauma/stress, and viral. Additional results, obtained from meta-analysis and confirmed by patient survey, were the common age of onset (early to mid-20s) and type of psoriasis (plaque; mild; symmetrical; scalp, chest, and extremities, specifically elbows and knees). Almost 70% of patients reported no prescription drug use due to severe side effects and prohibitive cost. These results will guide the development of psoriasis and psoriatic arthritis diagnostic test. The significant number of medical publications classified psoriatic arthritis disease as inflammatory of an unknown etiology. Thus numerous meta-analyses struggle to report any meaningful conclusions since no definitive results have been reported to date. Therefore, return to the basics is an essential step to any future meaningful results. To date, medical literature supports the fact that psoriatic disease in its current classification could be misidentifying subcategories, which in turn hinders the success of studies conducted to date. Moreover, there has been an enormous commercial support to pursue various immune-modulation therapies, thus following a narrow hypothesis/mechanism of action that is yet to yield resolution of disease state. Recurrence and complications may be considered unacceptable in a significant number of these studies. The aim of the ongoing study is to focus on a narrow subgroup of patient population, as identified by this exploratory study via meta-analysis and patient survey, and conduct an exhaustive work up, aiming at mechanism of action and causality before proposing a cure or therapeutic modality. Remission in psoriasis has been achieved and documented in medical literature, such as immune-modulation, phototherapy, various over-the-counter agents, including salts and tar. However, there is no psoriasis and psoriatic arthritis diagnostic test to date, to guide the diagnosis and treatment of this debilitating and, thus far, incurable disease. Because psoriasis affects approximately 2% of population, the results of this study may affect the treatment and improve the quality of life of a significant number of psoriasis patients, potentially millions of patients in the United States alone and many more millions worldwide.

Keywords: biologics, early diagnosis, etiology, immune disease, immune modulation therapy, inflammation skin disorder, phototherapy, plaque psoriasis, psoriasis, psoriasis classification, psoriasis disease marker, psoriasis diagnostic test, psoriasis marker, psoriasis mechanism of action, psoriasis treatment, psoriatic arthritis, psoriatic disease, psoriatic disease marker, psoriatic patient experience, psoriatic patient quality of life, remission, salt therapy, targeted immune therapy

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Authors: Tom S. Owens, Tom A. Calverley, Benjamin S. Stacey, Christopher J. Marley, George Rose, Lewis Fall, Gareth L. Jones, Priscilla Williams, John P. R. Williams, Martin Steggall, Damian M. Bailey

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Introduction and aims: Sports-related concussion (SRC) represents a significant and growing public health concern in rugby union, yet remains one of the least understood injuries facing the health community today. Alongside increasing SRC incidence rates, there is concern that prior recurrent concussion may contribute to long-term neurologic sequelae in later-life. This may be due to an accelerated decline in cerebral perfusion, a major risk factor for neurocognitive decline and neurodegeneration, though the underlying mechanisms remain to be established. The present study hypothesised that recurrent concussion in current professional rugby union players would result in elevated systemic oxidative-nitrosative stress, reflected by a free radical-mediated reduction in nitric oxide (NO) bioavailability and impaired cerebrovascular and cognitive function. Methodology: A longitudinal study design was adopted across the 2017-2018 rugby union season. Ethical approval was obtained from the University of South Wales Ethics Committee. Data collection is ongoing, and therefore the current report documents result from the pre-season and first half of the in-season data collection. Participants were initially divided into two subgroups; 23 professional rugby union players (aged 26 ± 5 years) and 22 non-concussed controls (27 ± 8 years). Pre-season measurements were performed for cerebrovascular function (Doppler ultrasound of middle cerebral artery velocity (MCAv) in response to hypocapnia/normocapnia/hypercapnia), cephalic venous concentrations of the ascorbate radical (A•-, electron paramagnetic resonance spectroscopy), NO (ozone-based chemiluminescence) and cognition (neuropsychometric tests). Notational analysis was performed to assess contact in the rugby group throughout each competitive game. Results: 1001 tackles and 62 injuries, including three concussions were observed across the first half of the season. However, no associations were apparent between number of tackles and any injury type (P > 0.05). The rugby group expressed greater oxidative stress as indicated by increased A•- (P < 0.05 vs. control) and a subsequent decrease in NO bioavailability (P < 0.05 vs. control). The rugby group performed worse in the Ray Auditory Verbal Learning Test B (RAVLT-B, learning, and memory) and the Grooved Pegboard test using both the dominant and non-dominant hands (visuomotor coordination, P < 0.05 vs. control). There were no between-group differences in cerebral perfusion at baseline (MCAv: 54 ± 13 vs. 59 ± 12, P > 0.05). Likewise, no between-group differences in CVRCO2Hypo (2.58 ± 1.01 vs. 2.58 ± 0.75, P > 0.05) or CVRCO2Hyper (2.69 ± 1.07 vs. 3.35 ± 1.28, P > 0.05) were observed. Conclusion: The present study identified that the rugby union players are characterized by impaired cognitive function subsequent to elevated systemic-oxidative-nitrosative stress. However, this appears to be independent of any functional impairment in cerebrovascular function. Given the potential long-term trajectory towards accelerated cognitive decline in populations exposed to SRC, prophylaxis to increase NO bioavailability warrants consideration.

Keywords: cognition, concussion, mild traumatic brain injury, rugby

Procedia PDF Downloads 178

Authors: George Charkoftakis, Panagiotis Liosatos, Nicolas-Alexander Tatlas, Dimitrios Goustouridis, Stelios M. Potirakis

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E-maintenance is a relatively new concept, generally referring to maintenance management by monitoring assets over the Internet. One of the key links in the chain of an e-maintenance system is data acquisition and transmission. Specifically for the case of a fleet of heavy-duty vehicles, where the main challenge is the diversity of the vehicles and vehicle-embedded self-diagnostic/reporting technologies, the design of the data acquisition and transmission unit is a demanding task. This clear if one takes into account that a heavy-vehicles fleet assortment may range from vehicles with only a limited number of analog sensors monitored by dashboard light indicators and gauges to vehicles with plethora of sensors monitored by a vehicle computer producing digital reporting. The present work proposes an adaptable internet of things (IoT) sensor node that is capable of addressing this challenge. The proposed sensor node architecture is based on the increasingly popular single-board computer – expansion boards approach. In the proposed solution, the expansion boards undertake the tasks of position identification by means of a global navigation satellite system (GNSS), cellular connectivity by means of 3G/long-term evolution (LTE) modem, connectivity to on-board diagnostics (OBD), and connectivity to analog and digital sensors by means of a novel design of expansion board. Specifically, the later provides eight analog plus three digital sensor channels, as well as one on-board temperature / relative humidity sensor. The specific device offers a number of adaptability features based on appropriate zero-ohm resistor placement and appropriate value selection for limited number of passive components. For example, although in the standard configuration four voltage analog channels with constant voltage sources for the power supply of the corresponding sensors are available, up to two of these voltage channels can be converted to provide power to the connected sensors by means of corresponding constant current source circuits, whereas all parameters of analog sensor power supply and matching circuits are fully configurable offering the advantage of covering a wide variety of industrial sensors. Note that a key feature of the proposed sensor node, ensuring the reliable operation of the connected sensors, is the appropriate supply of external power to the connected sensors and their proper matching to the IoT sensor node. In standard mode, the IoT sensor node communicates to the data center through 3G/LTE, transmitting all digital/digitized sensor data, IoT device identity, and position. Moreover, the proposed IoT sensor node offers WiFi connectivity to mobile devices (smartphones, tablets) equipped with an appropriate application for the manual registration of vehicle- and driver-specific information, and these data are also forwarded to the data center. All control and communication tasks of the IoT sensor node are performed by dedicated firmware. It is programmed with a high-level language (Python) on top of a modern operating system (Linux). Acknowledgment: This research has been co-financed by the European Union and Greek national funds through the Operational Program Competitiveness, Entrepreneurship, and Innovation, under the call RESEARCH—CREATE—INNOVATE (project code: T1EDK- 01359, IntelligentLogger).

Keywords: IoT sensor nodes, e-maintenance, single-board computers, sensor expansion boards, on-board diagnostics

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Authors: Enya Trenholm-Jensen

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This paper employs various semiotic methodologies to examine the mechanism of soft power. Soft power refers to a country’s global reputation and their ability to leverage that reputation to achieve certain aims. South Korea has invested heavily in their soft power strategy for a multitude of predominantly historical and geopolitical reasons. On account of this investment and the global prominence of their strategy, South Korea was considered to be the optimal candidate for the aims of this investigation. Having isolated the entertainment industry as one of the most heavily funded segments of the South Korean soft power strategy, the analysis restricted itself to this sector. Within this industry, two entertainment products were selected as case studies. The case studies were chosen based on commercial success according to metrics such as streams, purchases, and subsequent revenue. This criterion was deemed to be the most objective and verifiable indicator of the products general appeal. The entertainment products which met the chosen criterion were Netflix’ “Squid Game” and BTS’ hit single “Butter”. The methodologies employed were chosen according to the medium of the entertainment products. For “Squid Game,” an aesthetic analysis was carried out to investigate how multi- layered meanings were mobilized in a show popularized by its visual grammar. To examine “Butter”, both music semiology and linguistic analysis were employed. The music section featured an analysis underpinned by denotative and connotative music semiotic theories borrowing from scholars Theo van Leeuwen and Martin Irvine. The linguistic analysis focused on stance and semantic fields according to scholarship by George Yule and John W. DuBois. The aesthetic analysis of the first case study revealed intertextual references to famous artworks, which served to augment the emotional provocation of the Squid Game narrative. For the second case study, the findings exposed a set of musical meaning units arranged in a patchwork of familiar and futuristic elements to achieve a song that existed on the boundary between old and new. The linguistic analysis of the song’s lyrics found a deceptively innocuous surface level meaning that bore implications for authority, intimacy, and commercial success. Whether through means of visual metaphor, embedded auditory associations, or linguistic subtext, the collective findings of the three analyses exhibited a desire to conjure a form of positive arousal in the spectator. In the synthesis section, this process is likened to that of branding. Through an exploration of branding, the entertainment products can be understood as cogs in a larger operation aiming to create positive associations to Korea as a country and a concept. Limitations in the form of a timeframe biased perspective are addressed, and directions for future research are suggested. This paper employs semiotic methodologies to examine two entertainment products as mechanisms of soft power. Through means of visual metaphor, embedded auditory associations, or linguistic subtext, the findings reveal a desire to conjure positive arousal in the spectator. The synthesis finds similarities to branding, thus positioning the entertainment products as cogs in a larger operation aiming to create positive associations to Korea as a country and a concept.

Keywords: BTS, cognitive semiotics, entertainment, soft power, south korea, squid game

Procedia PDF Downloads 154

Authors: Areti Okalidou, Paul D. Hatzigiannakoglou, Aikaterini Vatou, George Kyriafinis

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Young children are nowadays adept at using technology. Hence, computer-based auditory training programs (CBATPs) have become increasingly popular in aural rehabilitation for children with hearing loss and/or with cochlear implants (CI). Yet, their clinical utility for prognostic, diagnostic, and monitoring purposes has not been explored. The purposes of the study were: a) to develop an updated version of the auditory rehabilitation tool for Greek-speaking children with cochlear implants, b) to develop a database for behavioral responses, and c) to compare accuracy rates and reaction times in children differing in hearing status and other medical and demographic characteristics, in order to assess the tool’s clinical utility in prognosis, diagnosis, and progress monitoring. The updated version of the auditory rehabilitation tool was developed on a tablet, retaining the User-Centered Design approach and the elements of the Virtual Reality (VR) serious game. The visual stimuli were farm animals acting in simple game scenarios designed to trigger children’s responses to animal sounds, names, and relevant sentences. Based on an extended version of Erber’s auditory development model, the VR game consisted of six stages, i.e., sound detection, sound discrimination, word discrimination, identification, comprehension of words in a carrier phrase, and comprehension of sentences. A familiarization stage (learning) was set prior to the game. Children’s tactile responses were recorded as correct, false, or impulsive, following a child-dependent set up of a valid delay time after stimulus offset for valid responses. Reaction times were also recorded, and the database was in Εxcel format. The tablet version of the auditory rehabilitation tool was piloted in 22 preschool children with Νormal Ηearing (ΝΗ), which led to improvements. The study took place in clinical settings or at children’s homes. Fifteen children with CI, aged 5;7-12;3 years with post-implantation 0;11-5;1 years used the auditory rehabilitation tool. Eight children with CI were monolingual, two were bilingual and five had additional disabilities. The control groups consisted of 13 children with ΝΗ, aged 2;6-9;11 years. A comparison of both accuracy rates, as percent correct, and reaction times (in sec) was made at each stage, across hearing status, age, and also, within the CI group, based on presence of additional disability and bilingualism. Both monolingual Greek-speaking children with CI with no additional disabilities and hearing peers showed high accuracy rates at all stages, with performances falling above the 3rd quartile. However, children with normal hearing scored higher than the children with CI, especially in the detection and word discrimination tasks. The reaction time differences between the two groups decreased in language-based tasks. Results for children with CI with additional disability or bilingualism varied. Finally, older children scored higher than younger ones in both groups (CI, NH), but larger differences occurred in children with CI. The interactions between familiarization of the software, age, hearing status and demographic characteristics are discussed. Overall, the VR game is a promising tool for tracking the development of auditory skills, as it provides multi-level longitudinal empirical data. Acknowledgment: This work is part of a project that has received funding from the Research Committee of the University of Macedonia under the Basic Research 2020-21 funding programme.

Keywords: VR serious games, auditory rehabilitation, auditory training, children with cochlear implants

Procedia PDF Downloads 89

Authors: Katarzyna Lubecka, Kirsty Flower, Megan Beetch, Lucinda Kurzava, Hannah Buvala, Samer Gawrieh, Suthat Liangpunsakul, Tracy Gonzalez, George McCabe, Naga Chalasani, James M. Flanagan, Barbara Stefanska

Abstract:

Hepatocellular carcinoma (HCC), the most prevalent type of primary liver cancer, is the second leading cause of cancer death worldwide. Late onset of clinical symptoms in HCC results in late diagnosis and poor disease outcome. Approximately 85% of individuals with HCC have underlying liver cirrhosis. However, not all cirrhotic patients develop cancer. Reliable early detection biomarkers that can distinguish cirrhotic patients who will develop cancer from those who will not are urgently needed and could increase the cure rate from 5% to 80%. We used Illumina-450K microarray to test whether blood DNA, an easily accessible source of DNA, bear site-specific changes in DNA methylation in response to HCC before diagnosis with conventional tools (pre-diagnostic). Top 11 differentially methylated sites were selected for validation by pyrosequencing. The diagnostic potential of the 11 pyrosequenced probes was tested in blood samples from a prospective cohort of cirrhotic patients. We identified 971 differentially methylated CpG sites in pre-diagnostic HCC cases as compared with healthy controls (P < 0.05, paired Wilcoxon test, ICC ≥ 0.5). Nearly 76% of differentially methylated CpG sites showed lower levels of methylation in cases vs. controls (P = 2.973E-11, Wilcoxon test). Classification of the CpG sites according to their location relative to CpG islands and transcription start site revealed that those hypomethylated loci are located in regulatory regions important for gene transcription such as CpG island shores, promoters, and 5’UTR at higher frequency than hypermethylated sites. Among 735 CpG sites hypomethylated in cases vs. controls, 482 sites were assigned to gene coding regions whereas 236 hypermethylated sites corresponded to 160 genes. Bioinformatics analysis using GO, KEGG and DAVID knowledgebase indicate that differentially methylated CpG sites are located in genes associated with functions that are essential for gene transcription, cell adhesion, cell migration, and regulation of signal transduction pathways. Taking into account the magnitude of the difference, statistical significance, location, and consistency across the majority of matched pairs case-control, we selected 11 CpG loci corresponding to 10 genes for further validation by pyrosequencing. We established that methylation of CpG sites within 5 out of those 10 genes distinguish cirrhotic patients who subsequently developed HCC from those who stayed cancer free (cirrhotic controls), demonstrating potential as biomarkers of early detection in populations at risk. The best predictive value was detected for CpGs located within BARD1 (AUC=0.70, asymptotic significance ˂0.01). Using an additive logistic regression model, we further showed that 9 CpG loci within those 5 genes, that were covered in pyrosequenced probes, constitute a panel with high diagnostic accuracy (AUC=0.887; 95% CI:0.80-0.98). The panel was able to distinguish pre-diagnostic cases from cirrhotic controls free of cancer with 88% sensitivity at 70% specificity. Using blood as a minimally invasive material and pyrosequencing as a straightforward quantitative method, the established biomarker panel has high potential to be developed into a routine clinical test after validation in larger cohorts. This study was supported by Showalter Trust, American Cancer Society (IRG#14-190-56), and Purdue Center for Cancer Research (P30 CA023168) granted to BS.

Keywords: biomarker, DNA methylation, early detection, hepatocellular carcinoma

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Authors: Bailey Houghtaling, Elena Serrano, Vivica Kraak, Samantha Harden, George Davis, Sarah Misyak

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United States (U.S.) Department of Agriculture Supplemental Nutrition Assistance Program (SNAP) participants are low-income Americans receiving federal dollars for supplemental food and beverage purchases. Participants use a variety of (traditional/non-traditional) SNAP-authorized stores for household dietary purchases - also representing food access points for all Americans. Importantly consumers' food and beverage purchases from non-traditional store formats tend to be higher in saturated fats, added sugars, and sodium when compared to purchases from traditional (e.g., grocery/supermarket) formats. Overconsumption of energy-dense and low-nutrient food and beverage products contribute to high obesity rates and adverse health outcomes that differ in severity among urban/rural U.S. locations and high/low-income populations. Little is known about the SNAP-authorized food store format landscape nationally, regionally, or by urban-rural status, as traditional formats are currently used as the gold standard in food access research. This research utilized publicly available U.S. databases to fill this large literature gap and to provide insight into modes of food access for vulnerable U.S. populations: (1) SNAP Retailer Locator which provides a list of all authorized food stores in the U.S., and; (2) Rural-Urban Continuum Codes (RUCC) that categorize U.S. counties as urban (RUCC 1-3) or rural (RUCC 4-9). Frequencies were determined for the highest occurring food store formats nationally and within two regionally diverse U.S. states – Virginia in the east and California in the west. Store format codes were assigned (e.g., grocery, drug, convenience, mass merchandiser, supercenter, dollar, club, or other). RUCC was applied to investigate state-level differences in urbanity-rurality regarding prevalent food store formats and Chi Square test of independence was used to determine if food store format distributions significantly (p < 0.05) differed by region or rurality. The resulting research sample that represented highly prevalent SNAP-authorized food stores nationally included 41.25% of all SNAP stores in the U.S. (N=257,839), comprised primarily of convenience formats (31.94%) followed by dollar (25.58%), drug (19.24%), traditional (10.87%), supercenter (6.85%), mass merchandiser (1.62%), non-food store or restaurant (1.81%), and club formats (1.09%). Results also indicated that the distribution of prevalent SNAP-authorized formats significantly differed by state. California had a lower proportion of traditional (9.96%) and a higher proportion of drug (28.92%) formats than Virginia- 11.55% and 19.97%, respectively (p < 0.001). Virginia also had a higher proportion of dollar formats (26.11%) when compared to California (10.64%) (p < 0.001). Significant differences were also observed for rurality variables (p < 0.001). Prominently, rural Virginia had a significantly higher proportion of dollar formats (41.71%) when compared to urban Virginia (21.78%) and rural California (21.21%). Non-traditional SNAP-authorized formats are highly prevalent and significantly differ in distribution by U.S. region and rurality. The largest proportional difference was observed for dollar formats where the least nutritious consumer purchases are documented in the literature. Researchers/practitioners should investigate non-traditional food stores at the local level using these research findings and similar applied methodologies to determine how access to various store formats impact obesity prevalence. For example, dollar stores may be prime targets for interventions to enhance nutritious consumer purchases in rural Virginia while targeting drug formats in California may be more appropriate.

Keywords: food access, food store format, nutrition interventions, SNAP consumers

Procedia PDF Downloads 141