Search results for: clinical advice services
Commenced in January 2007
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Edition: International
Paper Count: 7539

Search results for: clinical advice services

99 Computer-Integrated Surgery of the Human Brain, New Possibilities

Authors: Ugo Galvanetto, Pirto G. Pavan, Mirco Zaccariotto

Abstract:

The discipline of Computer-integrated surgery (CIS) will provide equipment able to improve the efficiency of healthcare systems and, which is more important, clinical results. Surgeons and machines will cooperate in new ways that will extend surgeons’ ability to train, plan and carry out surgery. Patient specific CIS of the brain requires several steps: 1 - Fast generation of brain models. Based on image recognition of MR images and equipped with artificial intelligence, image recognition techniques should differentiate among all brain tissues and segment them. After that, automatic mesh generation should create the mathematical model of the brain in which the various tissues (white matter, grey matter, cerebrospinal fluid …) are clearly located in the correct positions. 2 – Reliable and fast simulation of the surgical process. Computational mechanics will be the crucial aspect of the entire procedure. New algorithms will be used to simulate the mechanical behaviour of cutting through cerebral tissues. 3 – Real time provision of visual and haptic feedback A sophisticated human-machine interface based on ergonomics and psychology will provide the feedback to the surgeon. The present work will address in particular point 2. Modelling the cutting of soft tissue in a structure as complex as the human brain is an extremely challenging problem in computational mechanics. The finite element method (FEM), that accurately represents complex geometries and accounts for material and geometrical nonlinearities, is the most used computational tool to simulate the mechanical response of soft tissues. However, the main drawback of FEM lies in the mechanics theory on which it is based, classical continuum Mechanics, which assumes matter is a continuum with no discontinuity. FEM must resort to complex tools such as pre-defined cohesive zones, external phase-field variables, and demanding remeshing techniques to include discontinuities. However, all approaches to equip FEM computational methods with the capability to describe material separation, such as interface elements with cohesive zone models, X-FEM, element erosion, phase-field, have some drawbacks that make them unsuitable for surgery simulation. Interface elements require a-priori knowledge of crack paths. The use of XFEM in 3D is cumbersome. Element erosion does not conserve mass. The Phase Field approach adopts a diffusive crack model instead of describing true tissue separation typical of surgical procedures. Modelling discontinuities, so difficult when using computational approaches based on classical continuum Mechanics, is instead easy for novel computational methods based on Peridynamics (PD). PD is a non-local theory of mechanics formulated with no use of spatial derivatives. Its governing equations are valid at points or surfaces of discontinuity, and it is, therefore especially suited to describe crack propagation and fragmentation problems. Moreover, PD does not require any criterium to decide the direction of crack propagation or the conditions for crack branching or coalescence; in the PD-based computational methods, cracks develop spontaneously in the way which is the most convenient from an energy point of view. Therefore, in PD computational methods, crack propagation in 3D is as easy as it is in 2D, with a remarkable advantage with respect to all other computational techniques.

Keywords: computational mechanics, peridynamics, finite element, biomechanics

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98 A Computational Investigation of Potential Drugs for Cholesterol Regulation to Treat Alzheimer’s Disease

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

Abstract:

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

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

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97 Effect of a Nutritional Supplement Containing Euterpe oleracea Mart., Inulin, Phaseolus vulgaris and Caralluma fimbriata in Persons with Metabolic Syndrome

Authors: Eduardo Cabrera-Rode, Janet Rodriguez, Aimee Alvarez, Ragmila Echevarria, Antonio D. Reyes, Ileana Cubas-Duenas, Silvia E. Turcios, Oscar Diaz-Diaz

Abstract:

Obex is a nutritional supplement to help weight loss naturally. In addition, this supplement has a satiating effect that helps control the craving to eat between meals. The purpose of this study was to evaluate the effect of Obex in the metabolic syndrome (MS). This was an open label pilot study conducted in 30 patients with MS and ages between 29 and 60 years old. Participants received Obex, at a dose of one sachet before (30 to 45 minutes) the two main meals (lunch and dinner) daily (mean two sachets per day) for 3 months. The content of the sachets was dissolved in a glass of water or fruit juice. Obex ingredients: Açai (Euterpe oleracea Mart.) berry, inulin, Phaseolus vulgaris, Caralluma fimbriata, inositol, choline, arginine, ornitine, zinc sulfate, carnitine fumarate, methionine, calcium pantothenate, pyridoxine and folic acid. In addition to anthropometric measures and blood pressure, fasting plasma glucose, total cholesterol, triglycerides and HDL-cholesterol and insulin were determined. Insulin resistance was assessed by HOMA-IR index. Three indirect indexes were used to calculate insulin sensitivity [QUICKI index (Quantitative insulin sensitivity check index), Bennett index and Raynaud index]. Metabolic syndrome was defined according to the Joint Interim Statement (JIS) criteria. The JIS criteria require at least three of the following components: (1) abdominal obesity (waist circumference major or equal major or equal 94 cm for men or 80 cm for women), (2) triglycerides major or equal 1.7 mmol/L, (3) HDL cholesterol minor 1.03 mmol/L for men or minor 1.30 mmol/L for women, (4) systolic/diastolic blood pressure major or equal 130/85mmHg or use antihypertensive drugs, and (5) fasting plasma glucose major or equal 5.6 mmol/L or known treatment for diabetes. This study was approved by the Ethical and Research Committee of the National Institute of Endocrinology, Cuba and conducted according to the Declaration of Helsinki. Obex is registered as a food supplement in the National Institute of Nutrition and Food, Havana, Cuba. Written consent was obtained from all patients before the study. The clinical trial had been registered at ClinicalTrials.gov. After three months of treatment, 43.3% (13/30) of participants decreased the frequency of MS. Compared to baseline, Obex significantly reduced body weight, BMI, waist circumference, and waist/hip ratio and improved HDL-c (p<0.0001) and in addition to lowering blood pressure (p<0.05). After Obex intake, subjects also have shown a reduction in fasting plasma glucose (p<0.0001) and insulin sensitivity was enhanced (p=0.001). No adverse effects were seen in any of the participants during the study. In this pilot study, consumption of Obex decreased the prevalence of MS due to the improved selected components of the metabolic syndrome, indicating that further studies are warranted. Obex emerges as an effective and well tolerated treatment for preventing or delaying MS and therefore potential reduction of cardiovascular risk.

Keywords: nutritional supplement, metabolic syndrome, weight loss, insulin resistance

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

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

Abstract:

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

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

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95 Provotyping Futures Through Design

Authors: Elisabetta Cianfanelli, Maria Claudia Coppola, Margherita Tufarelli

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Design practices throughout history return a critical understanding of society since they always conveyed values and meanings aimed at (re)framing reality by acting in everyday life: here, design gains cultural and normative character, since its artifacts, services, and environments hold the power to intercept, influence and inspire thoughts, behaviors, and relationships. In this sense, design can be persuasive, engaging in the production of worlds and, as such, acting in the space between poietics and politics so that chasing preferable futures and their aesthetic strategies becomes a matter full of political responsibility. This resonates with contemporary landscapes of radical interdependencies challenging designers to focus on complex socio-technical systems and to better support values such as equality and justice for both humans and nonhumans. In fact, it is in times of crisis and structural uncertainty that designers turn into visionaries at the service of society, envisioning scenarios and dwelling in the territories of imagination to conceive new fictions and frictions to be added to the thickness of the real. Here, design’s main tasks are to develop options, to increase the variety of choices, to cultivate its role as scout, jester, agent provocateur for the public, so that design for transformation emerges, making an explicit commitment to society, furthering structural change in a proactive and synergic manner. However, the exploration of possible futures is both a trap and a trampoline because, although it embodies a radical research tool, it raises various challenges when the design process goes further in the translation of such vision into an artefact - whether tangible or intangible -, through which it should deliver that bit of future into everyday experience. Today designers are making up new tools and practices to tackle current wicked challenges, combining their approaches with other disciplinary domains: futuring through design, thus, rises from research strands like speculative design, design fiction, and critical design, where the blending of design approaches and futures thinking brings an action-oriented and product-based approach to strategic insights. The contribution positions at the intersection of those approaches, aiming at discussing design’s tools of inquiry through which it is possible to grasp the agency of imagined futures into present time. Since futures are not remote, they actively participate in creating path-dependent decisions, crystallized into designed artifacts par excellence, prototypes, and their conceptual other, provotypes: with both being unfinished and multifaceted, the first ones are effective in reiterating solutions to problems already framed, while the second ones prove to be useful when the goal is to explore and break boundaries, bringing closer preferable futures. By focusing on some provotypes throughout history which challenged markets and, above all, social and cultural structures, the contribution’s final aim is understanding the knowledge produced by provotypes, understood as design spaces where designs’s humanistic side might help developing a deeper sensibility about uncertainty and, most of all, the unfinished feature of societal artifacts, whose experimentation would leave marks and traces to build up f(r)ictions as vital sparks of plurality and collective life.

Keywords: speculative design, provotypes, design knowledge, political theory

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94 Narratives of Self-Renewal: Looking for A Middle Earth In-Between Psychoanalysis and the Search for Consciousness

Authors: Marilena Fatigante

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Contemporary psychoanalysis is increasingly acknowledging the existential demands of clients in psychotherapy. A significant aspect of the personal crises that patients face today is often rooted in the difficulty to find meaning in their own existence, even after working through or resolving traumatic memories and experiences. Tracing back to the correspondence between Freud and Romain Rolland (1927), psychoanalysis could not ignore that investigation of the psyche also encompasses the encounter with deep, psycho-sensory experiences, which involve a sense of "being one with the external world as a whole", the well-known “oceanic feeling”, as Rolland posed it. Despite the recognition of Non-ordinary States of Consciousness (NSC) as catalysts for transformation in clinical practice, highlighted by neuroscience and results from psychedelic-assisted therapies, there is few research on how psychoanalytic knowledge can integrate with other treatment traditions. These traditions, commonly rooted in non -Western, unconventional, and non-formal psychological knowledge, emphasize the individual’s innate tendency toward existential integrity and transcendence of self-boundaries. Inspired by an autobiographical account, this paper examines narratives of 12 individuals, who engaged in psychoanalytic therapy and also underwent treatment involving a non-formal helping relationship with an expert guide in consciousness, which included experience of this nature. The guide relies on 35 yrs of experience in Psychological, multidisciplinary studies in Human Sciences and Art, and demonstrates knowledge of many wisdom traditions, ranging from Eastern to Western philosophy, including Psychoanalysis and its development in cultural perspective (e.g, Ethnopsychiatry). Analyses focused primarily on two dimensions that research has identified as central in assessing the degree of treatment “success” in the patients’ narrative accounts of their therapies: agency and coherence, defined respectively as the increase, expressed in language, of the client’s perceived ability to manage his/her own challenges and the capacity, inherent in “narrative” itself as a resource for meaning making (Bruner, 1990), to provide the subject with a sense of unity, endowing his /her life experience with temporal and logical sequentiality. The present study reports that, in all narratives from the participants, agency and coherence are described differently than in “common” psychotherapy narratives. Although the participants consistently identified themselves as responsible agentic subject, the sense of agency derived from the non-conventional guidance pathway is never reduced to a personal, individual accomplishment. Rather, the more a new, fuller sense of “Life” (more than “Self”) develops out of the guidance pathway they engage with the expert guide, the more they “surrender” their own sense of autonomy and self-containment. Something, which Safran (2016) identified as well talking about the sense of surrender and “grace” in psychoanalytic sessions. Secondly, narratives of individuals engaging with the expert guide describe coherence not as repairing or enforcing continuity but as enhancing their ability to navigate dramatic discontinuities, falls, abrupt leaps and passages marked by feelings of loss and bereavement. The paper ultimately explores whether valid criteria can be established to analyze experiences of non-conventional paths of self-evolution. These paths are not opposed or alternative to conventional ones, and should not be simplistically dismissed as exotic or magical.

Keywords: oceanic feeling, non conventional guidance, consciousness, narratives, treatment outcomes

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93 Including All Citizens Pathway (IACP): Transforming Post-Secondary Education Using Inclusion and Accessibility as Foundation

Authors: Fiona Whittington-Walsh

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Including All Citizens Pathway (IACP) is addressing the systems wide discrimination that students with disabilities experience throughout the education system. IACP offers a wide, institutional support structure so that all students, including students with intellectual/developmental disabilities, are included and can succeed. The entire process from admissions, course selection, course instruction, graduation is designed to address systemic discrimination while supporting learners and faculty. The inclusive and accessible pedagogical model that is the foundation of IACP opens the doors of post-secondary education by making existing academic courses environments where all students can participate and succeed. IACP is about transforming teaching, not modifying, or adapting the curriculum or essential knowledge and skill sets that are required learning outcomes. Universal Design for Learning (UDL) principles are applied to instructional teaching strategies such as lectures, presentations, and assessment tools. Created in 2016 as a research pilot, IACP is one of the first fully inclusive for credit post-secondary options available. The pilot received numerous external and internal grants to support its initiative to investigate and assess the teaching strategies and techniques that support student learning of essential knowledge and skill sets. IACP pilot goals included: (1) provide a successful pilot as a model of inclusive and accessible pedagogy; (2) create a teacher’s guide to assist other instructors in transforming their teaching to reach a wide range of learners; (3) identify policy barriers located within the educational system; and (4) provide leadership and encouraging innovative and inclusive pedagogical practices. The pilot was a success and in 2020 the first cohort of students graduated with an exit credential that pre-exists IACP and consists of ten academic courses. The University has committed to continue IACP and has developed a sustainable model. Each new academic year a new cohort of IACP students starts their post-secondary educational journey, while two additional instructors are mentored with the pedagogy. The pedagogical foundation of IACP has far-reaching potential including, but not limited to, programs that offer services for international students whose first language is not English as well as influencing pedagogical reform in secondary and post-secondary education. IACP also supports universities in satisfying educational standards that are or will be included in accessibility/disability legislation. This session will present information about IACP, share examples of systems transformation, hear from students and instructors, and provide participatory experiential activities that demonstrate the transformative techniques. We will be drawing from the experiences of a recent course that explored research documenting the lived experiences of students with disabilities in post-secondary institutes in B.C (Whittington-Walsh). Students created theatrical scenes out of the data and presented it using Forum Theatre method. Forum Theatre was used to create conversations, challenge stereotypes, and build connections between ableism, disability justice, Indigeneity, and social policy.

Keywords: disability justice, inclusive education, pedagogical transformation, systems transformation

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92 A Bibliometric Analysis of Ukrainian Research Articles on SARS-COV-2 (COVID-19) in Compliance with the Standards of Current Research Information Systems

Authors: Sabina Auhunas

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These days in Ukraine, Open Science dramatically develops for the sake of scientists of all branches, providing an opportunity to take a more close look on the studies by foreign scientists, as well as to deliver their own scientific data to national and international journals. However, when it comes to the generalization of data on science activities by Ukrainian scientists, these data are often integrated into E-systems that operate inconsistent and barely related information sources. In order to resolve these issues, developed countries productively use E-systems, designed to store and manage research data, such as Current Research Information Systems that enable combining uncompiled data obtained from different sources. An algorithm for selecting SARS-CoV-2 research articles was designed, by means of which we collected the set of papers published by Ukrainian scientists and uploaded by August 1, 2020. Resulting metadata (document type, open access status, citation count, h-index, most cited documents, international research funding, author counts, the bibliographic relationship of journals) were taken from Scopus and Web of Science databases. The study also considered the info from COVID-19/SARS-CoV-2-related documents published from December 2019 to September 2020, directly from documents published by authors depending on territorial affiliation to Ukraine. These databases are enabled to get the necessary information for bibliometric analysis and necessary details: copyright, which may not be available in other databases (e.g., Science Direct). Search criteria and results for each online database were considered according to the WHO classification of the virus and the disease caused by this virus and represented (Table 1). First, we identified 89 research papers that provided us with the final data set after consolidation and removing duplication; however, only 56 papers were used for the analysis. The total number of documents by results from the WoS database came out at 21641 documents (48 affiliated to Ukraine among them) in the Scopus database came out at 32478 documents (41 affiliated to Ukraine among them). According to the publication activity of Ukrainian scientists, the following areas prevailed: Education, educational research (9 documents, 20.58%); Social Sciences, interdisciplinary (6 documents, 11.76%) and Economics (4 documents, 8.82%). The highest publication activity by institution types was reported in the Ministry of Education and Science of Ukraine (its percent of published scientific papers equals 36% or 7 documents), Danylo Halytsky Lviv National Medical University goes next (5 documents, 15%) and P. L. Shupyk National Medical Academy of Postgraduate Education (4 documents, 12%). Basically, research activities by Ukrainian scientists were funded by 5 entities: Belgian Development Cooperation, the National Institutes of Health (NIH, U.S.), The United States Department of Health & Human Services, grant from the Whitney and Betty MacMillan Center for International and Area Studies at Yale, a grant from the Yale Women Faculty Forum. Based on the results of the analysis, we obtained a set of published articles and preprints to be assessed on the variety of features in upcoming studies, including citation count, most cited documents, a bibliographic relationship of journals, reference linking. Further research on the development of the national scientific E-database continues using brand new analytical methods.

Keywords: content analysis, COVID-19, scientometrics, text mining

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91 Design Thinking and Project-Based Learning: Opportunities, Challenges, and Possibilities

Authors: Shoba Rathilal

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High unemployment rates and a shortage of experienced and qualified employees appear to be a paradox that currently plagues most countries worldwide. In a developing country like South Africa, the rate of unemployment is reported to be approximately 35%, the highest recorded globally. At the same time, a countrywide deficit in experienced and qualified potential employees is reported in South Africa, which is causing fierce rivalry among firms. Employers have reported that graduates are very rarely able to meet the demands of the job as there are gaps in their knowledge and conceptual understanding and other 21st-century competencies, attributes, and dispositions required to successfully negotiate the multiple responsibilities of employees in organizations. In addition, the rates of unemployment and suitability of graduates appear to be skewed by race and social class, the continued effects of a legacy of inequitable educational access. Higher Education in the current technologically advanced and dynamic world needs to serve as an agent of transformation, aspiring to develop graduates to be creative, flexible, critical, and with entrepreneurial acumen. This requires that higher education curricula and pedagogy require a re-envisioning of our selection, sequencing, and pacing of the learning, teaching, and assessment. At a particular Higher education Institution in South Africa, Design Thinking and Project Based learning are being adopted as two approaches that aim to enhance the student experience through the provision of a “distinctive education” that brings together disciplinary knowledge, professional engagement, technology, innovation, and entrepreneurship. Using these methodologies forces the students to solve real-time applied problems using various forms of knowledge and finding innovative solutions that can result in new products and services. The intention is to promote the development of skills for self-directed learning, facilitate the development of self-awareness, and contribute to students being active partners in the application and production of knowledge. These approaches emphasize active and collaborative learning, teamwork, conflict resolution, and problem-solving through effective integration of theory and practice. In principle, both these approaches are extremely impactful. However, at the institution in this study, the implementation of the PBL and DT was not as “smooth” as anticipated. This presentation reports on the analysis of the implementation of these two approaches within higher education curricula at a particular university in South Africa. The study adopts a qualitative case study design. Data were generated through the use of surveys, evaluation feedback at workshops, and content analysis of project reports. Data were analyzed using document analysis, content, and thematic analysis. Initial analysis shows that the forces constraining the implementation of PBL and DT range from the capacity to engage with DT and PBL, both from staff and students, educational contextual realities of higher education institutions, administrative processes, and resources. At the same time, the implementation of DT and PBL was enabled through the allocation of strategic funding and capacity development workshops. These factors, however, could not achieve maximum impact. In addition, the presentation will include recommendations on how DT and PBL could be adapted for differing contexts will be explored.

Keywords: design thinking, project based learning, innovative higher education pedagogy, student and staff capacity development

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90 Xen45 Gel Implant in Open Angle Glaucoma: Efficacy, Safety and Predictors of Outcome

Authors: Fossarello Maurizio, Mattana Giorgio, Tatti Filippo.

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The most widely performed surgical procedure in Open-Angle Glaucoma (OAG) is trabeculectomy. Although this filtering procedure is extremely effective, surgical failure and postoperative complications are reported. Due to the its invasive nature and possible complications, trabeculectomy is usually reserved, in practice, for patients who are refractory to medical and laser therapy. Recently, a number of micro-invasive surgical techniques (MIGS: Micro-Invasive Glaucoma Surgery), have been introduced in clinical practice. They meet the criteria of micro-incisional approach, minimal tissue damage, short surgical time, reliable IOP reduction, extremely high safety profile and rapid post-operative recovery. Xen45 Gel Implant (Allergan, Dublin, Ireland) is one of the MIGS alternatives, and consists in a porcine gelatin tube designed to create an aqueous flow from the anterior chamber to the subconjunctival space, bypassing the resistance of the trabecular meshwork. In this study we report the results of this technique as a favorable option in the treatment of OAG for its benefits in term of efficacy and safety, either alone or in combination with cataract surgery. This is a retrospective, single-center study conducted in consecutive OAG patients, who underwent Xen45 Gel Stent implantation alone or in combination with phacoemulsification, from October 2018 to June 2019. The primary endpoint of the study was to evaluate the reduction of both IOP and number of antiglaucoma medications at 12 months. The secondary endpoint was to correlate filtering bleb morphology evaluated by means of anterior segment OCT with efficacy in IOP lowering and eventual further procedures requirement. Data were recorded on Microsoft Excel and study analysis was performed using Microsoft Excel and SPSS (IBM). Mean values with standard deviations were calculated for IOPs and number of antiglaucoma medications at all points. Kolmogorov-Smirnov test showed that IOP followed a normal distribution at all time, therefore the paired Student’s T test was used to compare baseline and postoperative mean IOP. Correlation between postoperative Day 1 IOP and Month 12 IOP was evaluated using Pearson coefficient. Thirty-six eyes of 36 patients were evaluated. As compared to baseline, mean IOP and the mean number of antiglaucoma medications significantly decreased from 27,33 ± 7,67 mmHg to 16,3 ± 2,89 mmHg (38,8% reduction) and from 2,64 ± 1,39 to 0,42 ± 0,8 (84% reduction), respectively, at 12 months after surgery (both p < 0,001). According to bleb morphology, eyes were divided in uniform group (n=8, 22,2%), subconjunctival separation group (n=5, 13,9%), microcystic multiform group (n=9, 25%) and multiple internal layer group (n=14, 38,9%). Comparing to baseline, there was no significative difference in IOP between the 4 groups at month 12 follow-up visit. Adverse events included bleb function decrease (n=14, 38,9%), hypotony (n=8, 22,2%) and choroidal detachment (n=2, 5,6%). All eyes presenting bleb flattening underwent needling and MMC injection. The higher percentage of patients that required secondary needling was in the uniform group (75%), with a significant difference between the groups (p=0,03). Xen45 gel stent, either alone or in combination with phacoemulsification, provided a significant lowering in both IOP and medical antiglaucoma treatment and an elevated safety profile.

Keywords: anterior segment OCT, bleb morphology, micro-invasive glaucoma surgery, open angle glaucoma, Xen45 gel implant

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89 Exploring the Effect of Nursing Students’ Self-Directed Learning and Technology Acceptance through the Use of Digital Game-Based Learning in Medical Terminology Course

Authors: Hsin-Yu Lee, Ming-Zhong Li, Wen-Hsi Chiu, Su-Fen Cheng, Shwu-Wen Lin

Abstract:

Background: The use of medical terminology is essential to professional nurses on clinical practice. However, most nursing students consider traditional lecture-based teaching of medical terminology as boring and overly conceptual and lack motivation to learn. It is thus an issue to be discussed on how to enhance nursing students’ self-directed learning and improve learning outcomes of medical terminology. Digital game-based learning is a learner-centered way of learning. Past literature showed that the most common game-based learning for language education has been immersive games and teaching games. Thus, this study selected role-playing games (RPG) and digital puzzle games for observation and comparison. It is interesting to explore whether digital game-based learning has positive impact on nursing students’ learning of medical terminology and whether students can adapt well on this type of learning. Results can be used to provide references for institutes and teachers on teaching medical terminology. These instructions give you guidelines for preparing papers for the conference. Use this document as a template if you are using Microsoft Word. Otherwise, use this document as an instruction set. The electronic file of your paper will be formatted further at WASET. Define all symbols used in the abstract. Do not cite references in the abstract. Do not delete the blank line immediately above the abstract; it sets the footnote at the bottom of this column. Page margins are 1,78 cm top and down; 1,65 cm left and right. Each column width is 8,89 cm and the separation between the columns is 0,51 cm. Objective: The purpose of this research is to explore respectively the impact of RPG and puzzle game on nursing students’ self-directed learning and technology acceptance. The study further discusses whether different game types bring about different influences on students’ self-directed learning and technology acceptance. Methods: A quasi-experimental design was adopted in this study so that repeated measures between two groups could be conveniently conducted. 103 nursing students from a nursing college in Northern Taiwan participated in the study. For three weeks of experiment, the experiment group (n=52) received “traditional teaching + RPG” while the control group (n=51) received “traditional teaching + puzzle games”. Results: 1. On self-directed learning: For each game type, there were significant differences for the delayed tests of both groups as compared to the pre and post-tests of each group. However, there were no significant differences between the two game types. 2. On technology acceptance: For the experiment group, after the intervention of RPG, there were no significant differences concerning technology acceptance. For the control group, after the intervention of puzzle games, there were significant differences regarding technology acceptance. Pearson-correlation coefficient and path analysis conducted on the results of the two groups revealed that the dimension were highly correlated and reached statistical significance. Yet, the comparison of technology acceptance between the two game types did not reach statistical significance. Conclusion and Recommend: This study found that through using different digital games on learning, nursing students have effectively improved their self-directed learning. Students’ technology acceptances were also high for the two different digital game types and each dimension was significantly correlated. The results of the experimental group showed that through the scenarios of RPG, students had a deeper understanding of medical terminology, which reached the ‘Understand’ dimension of Bloom’s taxonomy. The results of the control group indicated that digital puzzle games could help students memorize and review medical terminology, which reached the ‘Remember’ dimension of Bloom’s taxonomy. The findings suggest that teachers of medical terminology could use digital games to assist their teaching according to their goals on cognitive learning. Adequate use of those games could help improve students’ self-directed learning and further enhance their learning outcome on medical terminology.

Keywords: digital game-based learning, medical terminology, nursing education, self-directed learning, technology acceptance model

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88 Cognitive Decline in People Living with HIV in India and Correlation with Neurometabolites Using 3T Magnetic Resonance Spectroscopy (MRS): A Cross-Sectional Study

Authors: Kartik Gupta, Virendra Kumar, Sanjeev Sinha, N. Jagannathan

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Introduction: A significant number of patients having human immunodeficiency virus (HIV) infection show a neurocognitive decline (NCD) ranging from minor cognitive impairment to severe dementia. The possible causes of NCD in HIV-infected patients include brain injury by HIV before cART, neurotoxic viral proteins and metabolic abnormalities. In the present study, we compared the level of NCD in asymptomatic HIV-infected patients with changes in brain metabolites measured by using magnetic resonance spectroscopy (MRS). Methods: 43 HIV-positive patients (30 males and 13 females) coming to ART center of the hospital and HIV-seronegative healthy subjects were recruited for the study. All the participants completed MRI and MRS examination, detailed clinical assessments and a battery of neuropsychological tests. All the MR investigations were carried out at 3.0T MRI scanner (Ingenia/Achieva, Philips, Netherlands). MRI examination protocol included the acquisition of T2-weighted imaging in axial, coronal and sagittal planes, T1-weighted, FLAIR, and DWI images in the axial plane. Patients who showed any apparent lesion on MRI were excluded from the study. T2-weighted images in three orthogonal planes were used to localize the voxel in left frontal lobe white matter (FWM) and left basal ganglia (BG) for single voxel MRS. Single voxel MRS spectra were acquired with a point resolved spectroscopy (PRESS) localization pulse sequence at an echo time (TE) of 35 ms and a repetition time (TR) of 2000 ms with 64 or 128 scans. Automated preprocessing and determination of absolute concentrations of metabolites were estimated using LCModel by water scaling method and the Cramer-Rao lower bounds for all metabolites analyzed in the study were below 15\%. Levels of total N-acetyl aspartate (tNAA), total choline (tCho), glutamate + glutamine (Glx), total creatine (tCr), were measured. Cognition was tested using a battery of tests validated for Indian population. The cognitive domains tested were the memory, attention-information processing, abstraction-executive, simple and complex perceptual motor skills. Z-scores normalized according to age, sex and education standard were used to calculate dysfunction in these individual domains. The NCD was defined as dysfunction with Z-score ≤ 2 in at least two domains. One-way ANOVA was used to compare the difference in brain metabolites between the patients and healthy subjects. Results: NCD was found in 23 (53%) patients. There was no significant difference in age, CD4 count and viral load between the two groups. Maximum impairment was found in the domains of memory and simple motor skills i.e., 19/43 (44%). The prevalence of deficit in attention-information processing, complex perceptual motor skills and abstraction-executive function was 37%, 35%, 33% respectively. Subjects with NCD had a higher level of Glutamate in the Frontal region (8.03 ± 2.30 v/s. 10.26 ± 5.24, p-value 0.001). Conclusion: Among newly diagnosed, ART-naïve retroviral disease patients from India, cognitive decline was found in 53\% patients using tests validated for this population. Those with neurocognitive decline had a significantly higher level of Glutamate in the left frontal region. There was no significant difference in age, CD4 count and viral load at initiation of ART between the two groups.

Keywords: HIV, neurocognitive decline, neurometabolites, magnetic resonance spectroscopy

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87 Understanding Different Facets of Chromosome Abnormalities: A 17-year Cytogenetic Study and Indian Perspectives

Authors: Lakshmi Rao Kandukuri, Mamata Deenadayal, Suma Prasad, Bipin Sethi, Srinadh Buragadda, Lalji Singh

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Worldwide; at least 7.6 million children are born annually with severe genetic or congenital malformations and among them 90% of these are born in mid and low-income countries. Precise prevalence data are difficult to collect, especially in developing countries, owing to the great diversity of conditions and also because many cases remain undiagnosed. The genetic and congenital disorder is the second most common cause of infant and childhood mortality and occurs with a prevalence of 25-60 per 1000 births. The higher prevalence of genetic diseases in a particular community may, however, be due to some social or cultural factors. Such factors include the tradition of consanguineous marriage, which results in a higher rate of autosomal recessive conditions including congenital malformations, stillbirths, or mental retardation. Genetic diseases can vary in severity, from being fatal before birth to requiring continuous management; their onset covers all life stages from infancy to old age. Those presenting at birth are particularly burdensome and may cause early death or life-long chronic morbidity. Genetic testing for several genetic diseases identifies changes in chromosomes, genes, or proteins. The results of a genetic test can confirm or rule out a suspected genetic condition or help determine a person's chance of developing or passing on a genetic disorder. Several hundred genetic tests are currently in use and more are being developed. Chromosomal abnormalities are the major cause of human suffering, which are implicated in mental retardation, congenital malformations, dysmorphic features, primary and secondary amenorrhea, reproductive wastage, infertility neoplastic diseases. Cytogenetic evaluation of patients is helpful in the counselling and management of affected individuals and families. We present here especially chromosomal abnormalities which form a major part of genetic disease burden in India. Different programmes on chromosome research and human reproductive genetics primarily relate to infertility since this is a major public health problem in our country, affecting 10-15 percent of couples. Prenatal diagnosis of chromosomal abnormalities in high-risk pregnancies helps in detecting chromosomally abnormal foetuses. Such couples are counselled regarding the continuation of pregnancy. In addition to the basic research, the team is providing chromosome diagnostic services that include conventional and advanced techniques for identifying various genetic defects. Other than routine chromosome diagnosis for infertility, also include patients with short stature, hypogonadism, undescended testis, microcephaly, delayed developmental milestones, familial, and isolated mental retardation, and cerebral palsy. Thus, chromosome diagnostics has found its applicability not only in disease prevention and management but also in guiding the clinicians in certain aspects of treatment. It would be appropriate to affirm that chromosomes are the images of life and they unequivocally mirror the states of human health. The importance of genetic counseling is increasing with the advancement in the field of genetics. The genetic counseling can help families to cope with emotional, psychological, and medical consequences of genetic diseases.

Keywords: India, chromosome abnormalities, genetic disorders, cytogenetic study

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86 The Multiplier Effects of Intelligent Transport System to Nigerian Economy

Authors: Festus Okotie

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Nigeria is the giant of Africa with great and diverse transport potentials yet to be fully tapped into and explored.it is the most populated nation in Africa with nearly 200 million people, the sixth largest oil producer overall and largest oil producer in Africa with proven oil and gas reserves of 37 billion barrels and 192 trillion cubic feet, over 300 square kilometers of arable land and significant deposits of largely untapped minerals. A world bank indicator which measures trading across border ranked Nigeria at 183 out of 185 countries in 2017 and although different governments in the past made efforts through different interventions such as 2007 ports reforms led by Ngozi Okonjo-Iweala, a former minister of Finance and world bank managing director also attempted to resolve some of the challenges such as infrastructure shortcomings, policy and regulatory inconsistencies, overlapping functions and duplicated roles among the different MDA’S. It is one of the fundamental structures smart nations and cities are using to improve the living conditions of its citizens and achieving sustainability. Examples of some of its benefits includes tracking high pedestrian areas, traffic patterns, railway stations, planning and scheduling bus times, it also enhances interoperability, creates alerts of transport situation and has swift capacity to share information among the different platforms and transport modes. It also offers a comprehensive approach to risk management, putting emergency procedures and response capabilities in place, identifying dangers, including vandalism or violence, fare evasion, and medical emergencies. The Nigerian transport system is urgently in need of modern infrastructures such as ITS. Smart city transport technology helps cities to function productively, while improving services for businesses and lives of is citizens. This technology has the ability to improve travel across traditional modes of transport, such as cars and buses, with immediate benefits for city dwellers and also helps in managing transport systems such as dangerous weather conditions, heavy traffic, and unsafe speeds which can result in accidents and loss of lives. Intelligent transportation systems help in traffic control such as permitting traffic lights to react to changing traffic patterns, instead of working on a fixed schedule in traffic. Intelligent transportation systems is very important in Nigeria’s transportation sector and so would require trained personnel to drive its efficiency to greater height because the purpose of introducing it is to add value and at the same time reduce motor vehicle miles and traffic congestion which is a major challenge around Tin can island and Apapa Port, a major transportation hub in Nigeria. The need for the federal government, state governments, houses of assembly to organise a national transportation workshop to begin the process of addressing the challenges in our nation’s transport sector is highly expedient and so bills that will facilitate the implementation of policies to promote intelligent transportation systems needs to be sponsored because of its potentials to create thousands of jobs for our citizens, provide farmers with better access to cities and a better living condition for Nigerians.

Keywords: intelligent, transport, system, Nigeria

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

Authors: Ahmad Saad, Shuja Abbas, Breanna Marine

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

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

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84 Traumatic Brain Injury Neurosurgical Care Continuum Delays in Mulago Hospital in Kampala Uganda

Authors: Silvia D. Vaca, Benjamin J. Kuo, Joao Ricardo Nickenig Vissoci, Catherine A. Staton, Linda W. Xu, Michael Muhumuza, Hussein Ssenyonjo, John Mukasa, Joel Kiryabwire, Henry E. Rice, Gerald A. Grant, Michael M. Haglund

Abstract:

Background: Patients with traumatic brain injury (TBI) can develop rapid neurological deterioration from swelling and intracranial hematomas, which can result in focal tissue ischemia, brain compression, and herniation. Moreover, delays in management increase the risk of secondary brain injury from hypoxemia and hypotension. Therefore, in TBI patients with subdural hematomas (SDHs) and epidural hematomas (EDHs), surgical intervention is both necessary and time sensitive. Significant delays are seen along the care continuum in low- and middle-income countries (LMICs) largely due to limited healthcare capacity to address the disproportional rates of TBI in Sub Saharan Africa (SSA). While many LMICs have subsidized systems to offset surgical costs, the burden of securing funds by the patients for medications, supplies, and CT diagnostics poses a significant challenge to timely surgical interventions. In Kampala Uganda, the challenge of obtaining timely CT scans is twofold: logistical and financial barriers. These bottlenecks contribute significantly to the care continuum delays and are associated with poor TBI outcomes. Objective: The objectives of this study are to 1) describe the temporal delays through a modified three delays model that fits the context of neurosurgical interventions for TBI patients in Kampala and 2) investigate the association between delays and mortality. Methods: Prospective data were collected for 563 TBI patients presenting to a tertiary hospital in Kampala from 1 June – 30 November 2016. Four time intervals were constructed along five time points: injury, hospital arrival, neurosurgical evaluation, CT results, and definitive surgery. Time interval differences among mild, moderate and severe TBI and their association with mortality were analyzed. Results: The mortality rate of all TBI patients presenting to MNRH was 9.6%, which ranged from 4.7% for mild and moderate TBI patients receiving surgery to 81.8% for severe TBI patients who failed to receive surgery. The duration from injury to surgery varied considerably across TBI severity with the largest gap seen between mild TBI (174 hours) and severe TBI (69 hours) patients. Further analysis revealed care continuum differences for interval 3 (neurosurgical evaluation to CT result) and 4 (CT result to surgery) between severe TBI patients (7 hours for interval 3 and 24 hours for interval 4) and mild TBI patients (19 hours for interval 3, and 96 hours for interval 4). These post-arrival delays were associated with mortality for mild (p=0.05) and moderate TBI (p=0.03) patients. Conclusions: To our knowledge, this is the first analysis using a modified 'three delays' framework to analyze the care continuum of TBI patients in Uganda from injury to surgery. We found significant associations between delays and mortality for mild and moderate TBI patients. As it currently stands, poorer outcomes were observed for these mild and moderate TBI patients who were managed non-operatively or failed to receive surgery while surgical services were shunted to more severely ill patients. While well intentioned, high mortality rates were still observed for the severe TBI patients managed surgically. These results suggest the need for future research to optimize triage practices, understand delay contributors, and improve pre-hospital logistical referral systems.

Keywords: care continuum, global neurosurgery, Kampala Uganda, LMIC, Mulago, traumatic brain injury

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83 Targeting Matrix Metalloprotease-9 to Reduce Coronary Artery Manifestations of Kawasaki’s Disease

Authors: Mohammadjavad Sotoudeheian, Navid Farahmandian

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Kawasaki disease (KD) is the primary cause of acquired pediatric heart disease as an acute vasculitis. In children with prolonged fever, rash, and inflammation of the mucosa KD must be considered as a clinical diagnosis. There is a persuasive suggestion of immune-mediated damage as the pathophysiologic cascade of KD. For example, the invasion of cytotoxic T-cells supports a viral etiology and the inflammasome of the innate immune system is a critical component in the vasculitis formation in KD. Animal models of KD propose the cytokine profiles, such as increased IL-1 and GM-CSF, which cause vascular damage. CRP and IFN-γ elevated expression and the upregulation of IL-6, and IL-10 production are also described in previous studies. Untreated KD is a critical risk factor for coronary artery diseases and myocardial infarction. Vascular damage may encompass amplified T-cell activity. SMAD3 is an essential molecule in down-regulating T-cells and increasing expression of FoxP3. It has a critical effect in the differentiation of regulatory T-cells. The discrepancy of regulatory T-cells and pro-inflammatory Th17 has been studied in acute coronary syndrome during KD. However in the coronary artery damaged lymphocytes and IgA plasma cells are seen at the lesion locations, the major immune cells in the coronary lesions are monocytes/macrophages and neutrophils. These cells secrete TNF-α, and activates matrix metalloprotease (MMP)-9, reducing the integrity of vessels and prompting patients to arise aneurysm. MMPs can break down the components of the extracellular matrix and assist immune cell movement. IVIG as an effective form of treatment clarified the role of the immune system, which may target pathogenic antigens and regulate cytokine production. Several reports have revealed that in the coronary arteries, high expression of MMP-9 in monocyte/macrophage results in pathologic cascades. Curcumin is a potent antioxidant and anti-inflammatory molecule. Curcumin decreases the production of reactive oxygen and nitrogen species and inhibits transcription factors like AP-1 and NF-κB. Curcumin also contains the characteristics of inhibitory effects on MMPs, especially MMP-9. The upregulation of MMP-9 is an important cellular response. Curcumin treatment caused a reverse effect and down-regulates MMP-9 gene expression which may fund the anti-inflammatory effect. Curcumin inhibits MMP-9 expression via PKC and AMPK-dependent pathways in Human monocytes cells. Elevated expression and activity of MMP-9 are correlated with advanced vascular lesions. AMPK controls lipid metabolism and oxidation, and protein synthesis. AMPK is also necessary for the MMP-9 activity and THP-1 cell adhesion to endothelial cells. Curcumin was shown to inhibit the activation of AMPKα. Compound C (AMPK inhibitor) inhibits MMP-9 expression level. Therefore, through inactivating AMPKs and PKC, curcumin decreases the MMP-9 level, which results in inhibiting monocyte/macrophage differentiation. Compound C also suppress the phosphorylation of three major classes of MAP kinase signaling, suggesting that curcumin may suppress MMP-9 level by inactivation of MAPK pathways. MAPK cascades are activated to induce the expression of MMP-9. Curcumin inhibits MAPKs phosphorylation, which contributes to the down-regulation of MMP-9. This study demonstrated that the potential inhibitory properties of curcumin over MMP-9 lead to a therapeutic strategy to reduce the risk of coronary artery involvement during KD.

Keywords: MMP-9, coronary artery aneurysm, Kawasaki’s disease, curcumin, AMPK, immune system, NF-κB, MAPK

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82 i2kit: A Tool for Immutable Infrastructure Deployments

Authors: Pablo Chico De Guzman, Cesar Sanchez

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Microservice architectures are increasingly in distributed cloud applications due to the advantages on the software composition, development speed, release cycle frequency and the business logic time to market. On the other hand, these architectures also introduce some challenges on the testing and release phases of applications. Container technology solves some of these issues by providing reproducible environments, easy of software distribution and isolation of processes. However, there are other issues that remain unsolved in current container technology when dealing with multiple machines, such as networking for multi-host communication, service discovery, load balancing or data persistency (even though some of these challenges are already solved by traditional cloud vendors in a very mature and widespread manner). Container cluster management tools, such as Kubernetes, Mesos or Docker Swarm, attempt to solve these problems by introducing a new control layer where the unit of deployment is the container (or the pod — a set of strongly related containers that must be deployed on the same machine). These tools are complex to configure and manage and they do not follow a pure immutable infrastructure approach since servers are reused between deployments. Indeed, these tools introduce dependencies at execution time for solving networking or service discovery problems. If an error on the control layer occurs, which would affect running applications, specific expertise is required to perform ad-hoc troubleshooting. As a consequence, it is not surprising that container cluster support is becoming a source of revenue for consulting services. This paper presents i2kit, a deployment tool based on the immutable infrastructure pattern, where the virtual machine is the unit of deployment. The input for i2kit is a declarative definition of a set of microservices, where each microservice is defined as a pod of containers. Microservices are built into machine images using linuxkit —- a tool for creating minimal linux distributions specialized in running containers. These machine images are then deployed to one or more virtual machines, which are exposed through a cloud vendor load balancer. Finally, the load balancer endpoint is set into other microservices using an environment variable, providing service discovery. The toolkit i2kit reuses the best ideas from container technology to solve problems like reproducible environments, process isolation, and software distribution, and at the same time relies on mature, proven cloud vendor technology for networking, load balancing and persistency. The result is a more robust system with no learning curve for troubleshooting running applications. We have implemented an open source prototype that transforms i2kit definitions into AWS cloud formation templates, where each microservice AMI (Amazon Machine Image) is created on the fly using linuxkit. Even though container cluster management tools have more flexibility for resource allocation optimization, we defend that adding a new control layer implies more important disadvantages. Resource allocation is greatly improved by using linuxkit, which introduces a very small footprint (around 35MB). Also, the system is more secure since linuxkit installs the minimum set of dependencies to run containers. The toolkit i2kit is currently under development at the IMDEA Software Institute.

Keywords: container, deployment, immutable infrastructure, microservice

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81 Benzenepropanamine Analogues as Non-detergent Microbicidal Spermicide for Effective Pre-exposure Prophylaxis

Authors: Veenu Bala, Yashpal S. Chhonker, Bhavana Kushwaha, Rabi S. Bhatta, Gopal Gupta, Vishnu L. Sharma

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According to UNAIDS 2013 estimate nearly 52% of all individuals living with HIV are now women of reproductive age (15–44 years). Seventy-five percent cases of HIV acquisition are through heterosexual contacts and sexually transmitted infections (STIs), attributable to unsafe sexual behaviour. Each year, an estimated 500 million people acquire atleast one of four STIs: chlamydia, gonorrhoea, syphilis and trichomoniasis. Trichomonas vaginalis (TV) is exclusively sexually transmitted in adults, accounting for 30% of STI cases and associated with pelvic inflammatory disease (PID), vaginitis and pregnancy complications in women. TV infection resulted in impaired vaginal milieu, eventually favoring HIV transmission. In the absence of an effective prophylactic HIV vaccine, prevention of new infections has become a priority. It was thought worthwhile to integrate HIV prevention and reproductive health services including unintended pregnancy protection for women as both are related with unprotected sex. Initially, nonoxynol-9 (N-9) had been proposed as a spermicidal agent with microbicidal activity but on the contrary it increased HIV susceptibility due to surfactant action. Thus, to accomplish an urgent need of novel woman controlled non-detergent microbicidal spermicides benzenepropanamine analogues have been synthesized. At first, five benzenepropanamine-dithiocarbamate hybrids have been synthesized and evaluated for their spermicidal, anti-Trichomonas and anti-fungal activities along with safety profiling to cervicovaginal cells. In order to further enhance the scope of above study benzenepropanamine was hybridized with thiourea as to introduce anti-HIV potential. The synthesized hybrid molecules were evaluated for their reverse transcriptase (RT) inhibition, spermicidal, anti-Trichomonas and antimicrobial activities as well as their safety against vaginal flora and cervical cells. simulated vaginal fluid (SVF) stability and pharmacokinetics of most potent compound versus N-9 was examined in female Newzealand (NZ) rabbits to observe its absorption into systemic circulation and subsequent exposure in blood plasma through vaginal wall. The study resulted in the most promising compound N-butyl-4-(3-oxo-3-phenylpropyl) piperazin-1-carbothioamide (29) exhibiting better activity profile than N-9 as it showed RT inhibition (72.30 %), anti-Trichomonas (MIC, 46.72 µM against MTZ susceptible and MIC, 187.68 µM against resistant strain), spermicidal (MEC, 0.01%) and antifungal activity (MIC, 3.12–50 µg/mL) against four fungal strains. The high safety against vaginal epithelium (HeLa cells) and compatibility with vaginal flora (lactobacillus), SVF stability and least vaginal absorption supported its suitability for topical vaginal application. Docking study was performed to gain an insight into the binding mode and interactions of the most promising compound, N-butyl-4-(3-oxo-3-phenylpropyl) piperazin-1-carbothioamide (29) with HIV-1 Reverse Transcriptase. The docking study has revealed that compound (29) interacted with HIV-1 RT similar to standard drug Nevirapine. It may be concluded that hybridization of benzenepropanamine and thiourea moiety resulted into novel lead with multiple activities including RT inhibition. A further lead optimization may result into effective vaginal microbicides having spermicidal, anti-Trichomonas, antifungal and anti-HIV potential altogether with enhanced safety to cervico-vaginal cells in comparison to Nonoxynol-9.

Keywords: microbicidal, nonoxynol-9, reverse transcriptase, spermicide

Procedia PDF Downloads 344
80 Supporting 'vulnerable' Students to Complete Their Studies During the Economic Crisis in Greece: The Umbrella Program of International Hellenic University

Authors: Rigas Kotsakis, Nikolaos Tsigilis, Vasilis Grammatikopoulos, Evridiki Zachopoulou

Abstract:

During the last decade, Greece has faced an unprecedented financial crisis, affecting various aspects and functionalities of Higher Education. Besides the restricted funding of academic institutions, the students and their families encountered economical difficulties that undoubtedly influenced the effective completion of their studies. In this context, a fairly large number of students in Alexander campus of International Hellenic University (IHU) delay, interrupt, or even abandon their studies, especially when they come from low-income families, belong to sensitive social or special needs groups, they have different cultural origins, etc. For this reason, a European project, named “Umbrella”, was initiated aiming at providing the necessary psychological support and counseling, especially to disadvantaged students, towards the completion of their studies. To this end, a network of various academic members (academic staff and students) from IHU, namely iMentor, were implicated in different roles. Specifically, experienced academic staff trained students to serve as intermediate links for the integration and educational support of students that fall into the aforementioned sensitive social groups and face problems for the completion of their studies. The main idea of the project is held upon its person-centered character, which facilitates direct student-to-student communication without the intervention of the teaching staff. The backbone of the iMentors network are senior students that face no problem in their academic life and volunteered for this project. It should be noted that there is a provision from the Umbrella structure for substantial and ethical rewards for their engagement. In this context, a well-defined, stringent methodology was implemented for the evaluation of the extent of the problem in IHU and the detection of the profile of the “candidate” disadvantaged students. The first phase included two steps, (a) data collection and (b) data cleansing/ preprocessing. The first step involved the data collection process from the Secretary Services of all Schools in IHU, from 1980 to 2019, which resulted in 96.418 records. The data set included the School name, the semester of studies, a student enrolling criteria, the nationality, the graduation year or the current, up-to-date academic state (still studying, delayed, dropped off, etc.). The second step of the employed methodology involved the data cleansing/preprocessing because of the existence of “noisy” data, missing and erroneous values, etc. Furthermore, several assumptions and grouping actions were imposed to achieve data homogeneity and an easy-to-interpret subsequent statistical analysis. Specifically, the duration of 40 years recording was limited to the last 15 years (2004-2019). In 2004 the Greek Technological Institutions were evolved into Higher Education Universities, leading into a stable and unified frame of graduate studies. In addition, the data concerning active students were excluded from the analysis since the initial processing effort was focused on the detection of factors/variables that differentiated graduate and deleted students. The final working dataset included 21.432 records with only two categories of students, those that have a degree and those who abandoned their studies. Findings of the first phase are presented across faculties and further discussed.

Keywords: higher education, students support, economic crisis, mentoring

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79 Menstrual Hygiene Practices Among the Women Age 15-24 in India

Authors: Priyanka Kumari

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Menstrual hygiene is an important aspect in the life of young girls. Menstrual Hygiene Management (MHM) is defined as ‘Women and adolescent girls using a clean material to absorb or collect menstrual blood that can be changed in privacy as often as necessary for the duration of the menstruation period, using soap and water for washing the body as required and having access to facilities to dispose of used menstrual management materials. This paper aims to investigate the prevalence of hygienic menstrual practices and socio-demographic correlates of hygienic menstrual practices among women aged 15-24 in India. Data from the 2015–2016 National Family Health Survey–4 for 244,500 menstruating women aged 15–24 were used. The methods have been categorized into two, women who use sanitary napkins, locally prepared napkins and tampons considered as a hygienic method and those who use cloth, any other method and nothing used at all during menstruation considered as an unhygienic method. Women’s age, year of schooling, religion, place of residence, caste/tribe, marital status, wealth index, type of toilet facility used, region, the structure of the house and exposure to mass media are taken as an independent variables. Bivariate analysis was carried out with selected background characteristics to analyze the socio-economic and demographic factors associated with the use of hygienic methods during menstruation. The odds for the use of the hygienic method were computed by employing binary logistic regression. Almost 60% of the women use cloth as an absorbent during menstruation to prevent blood stains from becoming evident. The hygienic method, which includes the use of locally prepared napkins, sanitary napkins and tampons, is 16.27%, 41.8% and 2.4%. The proportion of women who used hygienic methods to prevent blood stains from becoming evident was 57.58%. Multivariate analyses reveal that education of women, wealth and marital status are found to be the most important positive factors of hygienic menstrual practices. The structure of the house and exposure to mass media also have a positive impact on the use of menstrual hygiene practices. In contrast, women residing in rural areas belonging to scheduled tribes are less likely to use hygienic methods during their menstruation. Geographical regions are also statistically significant with the use of hygienic methods during menstruation. This study reveals that menstrual hygiene is not satisfactory among a large proportion of adolescent girls. They need more education about menstrual hygiene. A variety of factors affect menstrual behaviors; amongst these, the most influential is economic status, educational status and residential status, whether urban or rural. It is essential to design a mechanism to address and access healthy menstrual knowledge. It is important to encourage policies and quality standards that promote safe and affordable options and dynamic markets for menstrual products. Materials that are culturally acceptable, contextually available and affordable. Promotion of sustainable, environmentally friendly menstrual products and their disposal as it is a very important aspect of sustainable development goals. We also need to educate the girls about the services which are provided by the government, like a free supply of sanitary napkins to overcome reproductive tract infections. Awareness regarding the need for information on healthy menstrual practices is very important. It is essential to design a mechanism to address and access healthy menstrual practices. Emphasis should be given to the education of young girls about the importance of maintaining hygiene during menstruation to prevent the risk of reproductive tract infections.

Keywords: adolescent, menstruation, menstrual hygiene management, menstrual hygiene

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78 High Purity Lignin for Asphalt Applications: Using the Dawn Technology™ Wood Fractionation Process

Authors: Ed de Jong

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Avantium is a leading technology development company and a frontrunner in renewable chemistry. Avantium develops disruptive technologies that enable the production of sustainable high value products from renewable materials and actively seek out collaborations and partnerships with like-minded companies and academic institutions globally, to speed up introductions of chemical innovations in the marketplace. In addition, Avantium helps companies to accelerate their catalysis R&D to improve efficiencies and deliver increased sustainability, growth, and profits, by providing proprietary systems and services to this regard. Many chemical building blocks and materials can be produced from biomass, nowadays mainly from 1st generation based carbohydrates, but potential for competition with the human food chain leads brand-owners to look for strategies to transition from 1st to 2nd generation feedstock. The use of non-edible lignocellulosic feedstock is an equally attractive source to produce chemical intermediates and an important part of the solution addressing these global issues (Paris targets). Avantium’s Dawn Technology™ separates the glucose, mixed sugars, and lignin available in non-food agricultural and forestry residues such as wood chips, wheat straw, bagasse, empty fruit bunches or corn stover. The resulting very pure lignin is dense in energy and can be used for energy generation. However, such a material might preferably be deployed in higher added value applications. Bitumen, which is fossil based, are mostly used for paving applications. Traditional hot mix asphalt emits large quantities of the GHG’s CO₂, CH₄, and N₂O, which is unfavorable for obvious environmental reasons. Another challenge for the bitumen industry is that the petrochemical industry is becoming more and more efficient in breaking down higher chain hydrocarbons to lower chain hydrocarbons with higher added value than bitumen. This has a negative effect on the availability of bitumen. The asphalt market, as well as governments, are looking for alternatives with higher sustainability in terms of GHG emission. The usage of alternative sustainable binders, which can (partly) replace the bitumen, contributes to reduce GHG emissions and at the same time broadens the availability of binders. As lignin is a major component (around 25-30%) of lignocellulosic material, which includes terrestrial plants (e.g., trees, bushes, and grass) and agricultural residues (e.g., empty fruit bunches, corn stover, sugarcane bagasse, straw, etc.), it is globally highly available. The chemical structure shows resemblance with the structure of bitumen and could, therefore, be used as an alternative for bitumen in applications like roofing or asphalt. Applications such as the use of lignin in asphalt need both fundamental research as well as practical proof under relevant use conditions. From a fundamental point of view, rheological aspects, as well as mixing, are key criteria. From a practical point of view, behavior in real road conditions is key (how easy can the asphalt be prepared, how easy can it be applied on the road, what is the durability, etc.). The paper will discuss the fundamentals of the use of lignin as bitumen replacement as well as the status of the different demonstration projects in Europe using lignin as a partial bitumen replacement in asphalts and will especially present the results of using Dawn Technology™ lignin as partial replacement of bitumen.

Keywords: biorefinery, wood fractionation, lignin, asphalt, bitumen, sustainability

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77 Medical Decision-Making in Advanced Dementia from the Family Caregiver Perspective: A Qualitative Study

Authors: Elzbieta Sikorska-Simmons

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Advanced dementia is a progressive terminal brain disease that is accompanied by a syndrome of difficult to manage symptoms and complications that eventually lead to death. The management of advanced dementia poses major challenges to family caregivers who act as patient health care proxies in making medical treatment decisions. Little is known, however, about how they manage advanced dementia and how their treatment choices influence the quality of patient life. This prospective qualitative study examines the key medical treatment decisions that family caregivers make while managing advanced dementia. The term ‘family caregiver’ refers to a relative or a friend who is primarily responsible for managing patient’s medical care needs and legally authorized to give informed consent for medical treatments. Medical decision-making implies a process of choosing between treatment options in response to patient’s medical care needs (e.g., worsening comorbid conditions, pain, infections, acute medical events). Family caregivers engage in this process when they actively seek treatments or follow recommendations by healthcare professionals. Better understanding of medical decision-making from the family caregiver perspective is needed to design interventions that maximize the quality of patient life and limit inappropriate treatments. Data were collected in three waves of semi-structured interviews with 20 family caregivers for patients with advanced dementia. A purposive sample of 20 family caregivers was recruited from a senior care center in Central Florida. The qualitative personal interviews were conducted by the author in 4-5 months intervals. The ethical approval for the study was obtained prior to the data collection. Advanced dementia was operationalized as stage five or higher on the Global Deterioration Scale (GDS) (i.e., starting with the GDS score of five, patients are no longer able survive without assistance due to major cognitive and functional impairments). Information about patients’ GDS scores was obtained from the Center’s Medical Director, who had an in-depth knowledge of each patient’s health and medical treatment history. All interviews were audiotaped and transcribed verbatim. The qualitative data analysis was conducted to answer the following research questions: 1) what treatment decisions do family caregivers make while managing the symptoms of advanced dementia and 2) how do these treatment decisions influence the quality of patient life? To validate the results, the author asked each participating family caregiver if the summarized findings accurately captured his/her experiences. The identified medical decisions ranged from seeking specialist medical care to end-of-life care. The most common decisions were related to arranging medical appointments, medication management, seeking treatments for pain and other symptoms, nursing home placement, and accessing community-based healthcare services. The most challenging and consequential decisions were related to the management of acute complications, hospitalizations, and discontinuation of treatments. Decisions that had the greatest impact on the quality of patient life and survival were triggered by traumatic falls, worsening psychiatric symptoms, and aspiration pneumonia. The study findings have important implications for geriatric nurses in the context of patient/caregiver-centered dementia care. Innovative nursing approaches are needed to support family caregivers to effectively manage medical care needs of patients with advanced dementia.

Keywords: advanced dementia, family caregiver, medical decision-making, symptom management

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76 Linguistic Insights Improve Semantic Technology in Medical Research and Patient Self-Management Contexts

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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75 Chronic Progressive External Ophthalmoplegia (CPEO)

Authors: Gagandeep Singh Digra, Pawan Kumar, Mandeep Kaur Sidhu

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INTRODUCTION: Chronic Progressive External Ophthalmoplegia (CPEO), also known as Progressive External Ophthalmoplegia (PEO), is a type of eye disorder characterized by a loss of the muscle functions involved in eye and eyelid movement. CPEO can be caused by mutations in mitochondrial DNA. It typically manifests in young adults with bilateral and progressive ptosis as the most common presentation but can also present with difficulty swallowing (dysphagia) and general weakness of the skeletal muscles (myopathy), particularly in the neck, arms, or legs. CASE PRESENTATION: This is a case discussion of 3 cousins who presented to our clinic. A 23-year-old male with past surgical history (PSH) of ptosis repair 2 years ago presented with a chief complaint of nasal intonation for 1.5 years associated with difficulty swallowing. The patient also complained of nasal regurgitation of liquids. He denied any headaches, fever, seizures, weakness of arms or legs, urinary complaints or changes in bowel habits. Physical Examination was positive for facial muscle weakness, including an inability to lift eyebrows (Frontalis), inability to close eyes tightly (Orbicularis Oculi), corneal reflex absent bilaterally, difficulty clenching jaw (Masseter muscle), difficulty smiling (Zygomaticus major), inability to elevate upper lip (Zygomaticus minor). Another cousin of the first patient, a 25-year-old male with no past medical history, presented with complaints of nasal intonation for 2 years associated with difficulty swallowing. He denied a history of nasal regurgitation, headaches, fever, seizures, weakness, urinary complaints or changes in bowel habits. Physical Examination showed facial muscle weakness of the Frontalis muscle, Orbicularis Oculi muscle, Masseter Muscle, Zygomaticus Major, Zygomaticus Minor and absent corneal reflexes. A 28-year-old male, a cousin of the first two patients, presented with chief complaints of ptosis and nasal intonation for the last 8 years. He also complained of difficulty swallowing and nasal regurgitation of liquids. His physical examination showed facial muscle weakness, including frontalis muscle (inability to lift eyebrows), Orbicularis Oculi (inability to close eyes tightly), absent corneal reflexes bilaterally, Zygomaticus Major (difficulty smiling), and Zygomaticus Minor (inability to elevate upper lip). MRI brain and visual field of all the patients were normal. Differential diagnoses, including Grave’s disease, Myasthenia Gravis and Glioma, were ruled out. Due to financial reasons, muscle biopsy could not be pursued. Pedigree analysis revealed only males were affected, likely due to maternal inheritance, so the clinical diagnosis of CPEO was made. The patients underwent symptomatic management, including ptosis surgical correction for the third patient. CONCLUSION: Chronic Progressive External Ophthalmoplegia (CPEO), a rare case entity, occurs in young adults as a manifestation of mitochondrial myopathy. There are three modes of transmission- maternal transmission associated with mitochondrial point mutations, autosomal recessive, and autosomal dominant. CPEO can sometimes be difficult to diagnose, especially in asymmetric presentation. Therefore, it is crucial to keep it in differential diagnosis to avoid delay in diagnosis.

Keywords: neurology, chronic, progressive, ophthalmoplegia

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74 Global Evidence on the Seasonality of Enteric Infections, Malnutrition, and Livestock Ownership

Authors: Aishwarya Venkat, Anastasia Marshak, Ryan B. Simpson, Elena N. Naumova

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Livestock ownership is simultaneously linked to improved nutritional status through increased availability of animal-source protein, and increased risk of enteric infections through higher exposure to contaminated water sources. Agrarian and agro-pastoral households, especially those with cattle, goats, and sheep, are highly dependent on seasonally various environmental conditions, which directly impact nutrition and health. This study explores global spatiotemporally explicit evidence regarding the relationship between livestock ownership, enteric infections, and malnutrition. Seasonal and cyclical fluctuations, as well as mediating effects, are further examined to elucidate health and nutrition outcomes of individual and communal livestock ownership. The US Agency for International Development’s Demographic and Health Surveys (DHS) and the United Nations International Children's Emergency Fund’s Multi-Indicator Cluster Surveys (MICS) provide valuable sources of household-level information on anthropometry, asset ownership, and disease outcomes. These data are especially important in data-sparse regions, where surveys may only be conducted in the aftermath of emergencies. Child-level disease history, anthropometry, and household-level asset ownership information have been collected since DHS-V (2003-present) and MICS-III (2005-present). This analysis combines over 15 years of survey data from DHS and MICS to study 2,466,257 children under age five from 82 countries. Subnational (administrative level 1) measures of diarrhea prevalence, mean livestock ownership by type, mean and median anthropometric measures (height for age, weight for age, and weight for height) were investigated. Effects of several environmental, market, community, and household-level determinants were studied. Such covariates included precipitation, temperature, vegetation, the market price of staple cereals and animal source proteins, conflict events, livelihood zones, wealth indices and access to water, sanitation, hygiene, and public health services. Children aged 0 – 6 months, 6 months – 2 years, and 2 – 5 years of age were compared separately. All observations were standardized to interview day of year, and administrative units were harmonized for consistent comparisons over time. Geographically weighted regressions were constructed for each outcome and subnational unit. Preliminary results demonstrate the importance of accounting for seasonality in concurrent assessments of malnutrition and enteric infections. Household assets, including livestock, often determine the intensity of these outcomes. In many regions, livestock ownership affects seasonal fluxes in malnutrition and enteric infections, which are also directly affected by environmental and local factors. Regression analysis demonstrates the spatiotemporal variability in nutrition outcomes due to a variety of causal factors. This analysis presents a synthesis of evidence from global survey data on the interrelationship between enteric infections, malnutrition, and livestock. These results provide a starting point for locally appropriate interventions designed to address this nexus in a timely manner and simultaneously improve health, nutrition, and livelihoods.

Keywords: diarrhea, enteric infections, households, livestock, malnutrition, seasonality

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73 Using Health Literacy and Medico-Legal Guidance to Improve Restorative Dentistry Patient Information Leaflets

Authors: Hasneet K. Kalsi, Julie K. Kilgariff

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Introduction: Within dentistry, the process for gaining informed consent has become more complex. To consent for treatment, patients must understand all reasonable treatment options and associated risks and benefits. Consenting is therefore deeply embedded in health literacy. Patients attending for dental consultation are often presented with an array of information and choices, yet studies show patients recall less than half of the information provided immediately after. Appropriate and comprehensible patient information leaflets (PILs) may be useful aid memories. In 2016 the World Health Organisation set improving health literacy as a global priority. Soon after, Scotland’s 2017-2025 Making it Easier: A Health Literacy Action Plan followed. This project involved the review of Restorative PILs used within Dundee Dental Hospital to assess the Content and Readability. Method: The current PIL on Root Canal Treatment (RCT) was created in 2011. This predates the Montgomery vs. NHS Lanarkshire case, a ruling which significantly impacted dental consenting processes, as well as General Dental Council’s (GDC’s) Standards for the Dental Team and Faculty of General Dental Practice’s Good Practice Guidance on Clinical Examination and Record-Keeping. Current evidence-based guidance, including that stipulated by the GDC, was reviewed. A 20-point Essential Content Checklist was designed to conform to best practice guidance for valid consenting processes. The RCT leaflet was scored against this to ascertain if the content was satisfactory. Having ensured the content satisfied medicolegal requirements, health literacy considerations were reviewed regarding readability. This was assessed using McLaughlin’s Simple Measure of Gobbledygook (SMOG) formula, which identifies school stages that would have to be achieved to comprehend the PIL. The sensitivity of the results to alternative readability methods were assessed. Results: The PIL was not sufficient for modern consenting processes and reflected a suboptimal level of health literacy. Evaluation of the leaflet revealed key content was missing, including information pertaining to risks and benefits. Only five points out of the 20-point checklist were present. The readability score was 16, equivalent to a level 2 in National Adult Literacy Standards/Scottish Credit and Qualification Framework Level 5; 62% of Scottish adults are able to read to this standard. Discussion: Assessment of the leaflet showed it was no longer fit for purpose. Reasons include a lack of pertinent information, a text-heavy leaflet lacking flow, and content errors. The SMOG score indicates a high level of comprehension is required to understand this PIL, which many patients may not possess. A new PIL, compliant with medicolegal and health literacy guidance, was designed with patient-driven checklists, notes spaces for annotations/ questions and areas for clinicians to highlight important case-specific information. It has been tested using the SMOG formula. Conclusion: PILs can be extremely useful. Studies show that interactive use can enhance their effectiveness. PILs should reflect best practice guidance and be understood by patients. The 2020 leaflet designed and implemented aims to fulfill the needs of a modern healthcare system and its service users. It embraces and embeds Scotland’s Health Literacy Action Plan within the consenting process. A review of further leaflets using this model is ongoing.

Keywords: consent, health literacy, patient information leaflet, restorative dentistry

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72 Deep Learning Based on Image Decomposition for Restoration of Intrinsic Representation

Authors: Hyohun Kim, Dongwha Shin, Yeonseok Kim, Ji-Su Ahn, Kensuke Nakamura, Dongeun Choi, Byung-Woo Hong

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Artefacts are commonly encountered in the imaging process of clinical computed tomography (CT) where the artefact refers to any systematic discrepancy between the reconstructed observation and the true attenuation coefficient of the object. It is known that CT images are inherently more prone to artefacts due to its image formation process where a large number of independent detectors are involved, and they are assumed to yield consistent measurements. There are a number of different artefact types including noise, beam hardening, scatter, pseudo-enhancement, motion, helical, ring, and metal artefacts, which cause serious difficulties in reading images. Thus, it is desired to remove nuisance factors from the degraded image leaving the fundamental intrinsic information that can provide better interpretation of the anatomical and pathological characteristics. However, it is considered as a difficult task due to the high dimensionality and variability of data to be recovered, which naturally motivates the use of machine learning techniques. We propose an image restoration algorithm based on the deep neural network framework where the denoising auto-encoders are stacked building multiple layers. The denoising auto-encoder is a variant of a classical auto-encoder that takes an input data and maps it to a hidden representation through a deterministic mapping using a non-linear activation function. The latent representation is then mapped back into a reconstruction the size of which is the same as the size of the input data. The reconstruction error can be measured by the traditional squared error assuming the residual follows a normal distribution. In addition to the designed loss function, an effective regularization scheme using residual-driven dropout determined based on the gradient at each layer. The optimal weights are computed by the classical stochastic gradient descent algorithm combined with the back-propagation algorithm. In our algorithm, we initially decompose an input image into its intrinsic representation and the nuisance factors including artefacts based on the classical Total Variation problem that can be efficiently optimized by the convex optimization algorithm such as primal-dual method. The intrinsic forms of the input images are provided to the deep denosing auto-encoders with their original forms in the training phase. In the testing phase, a given image is first decomposed into the intrinsic form and then provided to the trained network to obtain its reconstruction. We apply our algorithm to the restoration of the corrupted CT images by the artefacts. It is shown that our algorithm improves the readability and enhances the anatomical and pathological properties of the object. The quantitative evaluation is performed in terms of the PSNR, and the qualitative evaluation provides significant improvement in reading images despite degrading artefacts. The experimental results indicate the potential of our algorithm as a prior solution to the image interpretation tasks in a variety of medical imaging applications. This work was supported by the MISP(Ministry of Science and ICT), Korea, under the National Program for Excellence in SW (20170001000011001) supervised by the IITP(Institute for Information and Communications Technology Promotion).

Keywords: auto-encoder neural network, CT image artefact, deep learning, intrinsic image representation, noise reduction, total variation

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71 Impact of Increased Radiology Staffing on After-Hours Radiology Reporting Efficiency and Quality

Authors: Peregrine James Dalziel, Philip Vu Tran

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Objective / Introduction: Demand for radiology services from Emergency Departments (ED) continues to increase with greater demands placed on radiology staff providing reports for the management of complex cases. Queuing theory indicates that wide variability of process time with the random nature of request arrival increases the probability of significant queues. This can lead to delays in the time-to-availability of radiology reports (TTA-RR) and potentially impaired ED patient flow. In addition, greater “cognitive workload” of greater volume may lead to reduced productivity and increased errors. We sought to quantify the potential ED flow improvements obtainable from increased radiology providers serving 3 public hospitals in Melbourne Australia. We sought to assess the potential productivity gains, quality improvement and the cost-effectiveness of increased labor inputs. Methods & Materials: The Western Health Medical Imaging Department moved from single resident coverage on weekend days 8:30 am-10:30 pm to a limited period of 2 resident coverage 1 pm-6 pm on both weekend days. The TTA-RR for weekend CT scans was calculated from the PACs database for the 8 month period symmetrically around the date of staffing change. A multivariate linear regression model was developed to isolate the improvement in TTA-RR, between the two 4-months periods. Daily and hourly scan volume at the time of each CT scan was calculated to assess the impact of varying department workload. To assess any improvement in report quality/errors a random sample of 200 studies was assessed to compare the average number of clinically significant over-read addendums to reports between the 2 periods. Cost-effectiveness was assessed by comparing the marginal cost of additional staffing against a conservative estimate of the economic benefit of improved ED patient throughput using the Australian national insurance rebate for private ED attendance as a revenue proxy. Results: The primary resident on call and the type of scan accounted for most of the explained variability in time to report availability (R2=0.29). Increasing daily volume and hourly volume was associated with increased TTA-RR (1.5m (p<0.01) and 4.8m (p<0.01) respectively per additional scan ordered within each time frame. Reports were available 25.9 minutes sooner on average in the 4 months post-implementation of double coverage (p<0.01) with additional 23.6 minutes improvement when 2 residents were on-site concomitantly (p<0.01). The aggregate average improvement in TTA-RR was 24.8 hours per weekend day This represents the increased decision-making time available to ED physicians and potential improvement in ED bed utilisation. 5% of reports from the intervention period contained clinically significant addendums vs 7% in the single resident period but this was not statistically significant (p=0.7). The marginal cost was less than the anticipated economic benefit based assuming a 50% capture of improved TTA-RR inpatient disposition and using the lowest available national insurance rebate as a proxy for economic benefit. Conclusion: TTA-RR improved significantly during the period of increased staff availability, both during the specific period of increased staffing and throughout the day. Increased labor utilisation is cost-effective compared with the potential improved productivity for ED cases requiring CT imaging.

Keywords: workflow, quality, administration, CT, staffing

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70 Image Segmentation with Deep Learning of Prostate Cancer Bone Metastases on Computed Tomography

Authors: Joseph M. Rich, Vinay A. Duddalwar, Assad A. Oberai

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Prostate adenocarcinoma is the most common cancer in males, with osseous metastases as the commonest site of metastatic prostate carcinoma (mPC). Treatment monitoring is based on the evaluation and characterization of lesions on multiple imaging studies, including Computed Tomography (CT). Monitoring of the osseous disease burden, including follow-up of lesions and identification and characterization of new lesions, is a laborious task for radiologists. Deep learning algorithms are increasingly used to perform tasks such as identification and segmentation for osseous metastatic disease and provide accurate information regarding metastatic burden. Here, nnUNet was used to produce a model which can segment CT scan images of prostate adenocarcinoma vertebral bone metastatic lesions. nnUNet is an open-source Python package that adds optimizations to deep learning-based UNet architecture but has not been extensively combined with transfer learning techniques due to the absence of a readily available functionality of this method. The IRB-approved study data set includes imaging studies from patients with mPC who were enrolled in clinical trials at the University of Southern California (USC) Health Science Campus and Los Angeles County (LAC)/USC medical center. Manual segmentation of metastatic lesions was completed by an expert radiologist Dr. Vinay Duddalwar (20+ years in radiology and oncologic imaging), to serve as ground truths for the automated segmentation. Despite nnUNet’s success on some medical segmentation tasks, it only produced an average Dice Similarity Coefficient (DSC) of 0.31 on the USC dataset. DSC results fell in a bimodal distribution, with most scores falling either over 0.66 (reasonably accurate) or at 0 (no lesion detected). Applying more aggressive data augmentation techniques dropped the DSC to 0.15, and reducing the number of epochs reduced the DSC to below 0.1. Datasets have been identified for transfer learning, which involve balancing between size and similarity of the dataset. Identified datasets include the Pancreas data from the Medical Segmentation Decathlon, Pelvic Reference Data, and CT volumes with multiple organ segmentations (CT-ORG). Some of the challenges of producing an accurate model from the USC dataset include small dataset size (115 images), 2D data (as nnUNet generally performs better on 3D data), and the limited amount of public data capturing annotated CT images of bone lesions. Optimizations and improvements will be made by applying transfer learning and generative methods, including incorporating generative adversarial networks and diffusion models in order to augment the dataset. Performance with different libraries, including MONAI and custom architectures with Pytorch, will be compared. In the future, molecular correlations will be tracked with radiologic features for the purpose of multimodal composite biomarker identification. Once validated, these models will be incorporated into evaluation workflows to optimize radiologist evaluation. Our work demonstrates the challenges of applying automated image segmentation to small medical datasets and lays a foundation for techniques to improve performance. As machine learning models become increasingly incorporated into the workflow of radiologists, these findings will help improve the speed and accuracy of vertebral metastatic lesions detection.

Keywords: deep learning, image segmentation, medicine, nnUNet, prostate carcinoma, radiomics

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