Search results for: multimodal

Authors: P. T. Collett, M. Kershaw

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Introduction: The discussion regarding which method of anesthesia provides better results for lower limb arthroplasty is a continuing debate. Multiple meta-analysis has been performed with no clear consensus. The current recommendation is to use neuraxial anesthesia for lower limb arthroplasty; however, the evidence to support this decision is weak. The Enhanced Recovery After Surgery (ERAS) society has recommended, either technique can be used as part of a multimodal anesthetic regimen. A local study was performed to see if the current anesthetic practice correlates with the current recommendations and to evaluate the efficacy of the different techniques utilized. Method: 90 patients who underwent total hip or total knee replacements at Nevill Hall Hospital between February 2019 to July 2019 were reviewed. Data collected included the anesthetic technique, day one opiate use, pain score, and length of stay. The data was collected from anesthetic charts, and the pain team follows up forms. Analysis: The average of patients undergoing lower limb arthroplasty was 70. Of those 83% (n=75) received a spinal anaesthetic and 17% (n=15) received a general anaesthetic. For patients undergoing knee replacement under general anesthetic the average day, one pain score was 2.29 and 1.94 if a spinal anesthetic was performed. For hip replacements, the scores were 1.87 and 1.8, respectively. There was no statistical significance between these scores. Day 1 opiate usage was significantly higher in knee replacement patients who were given a general anesthetic (45.7mg IV morphine equivalent) vs. those who were operated on under spinal anesthetic (19.7mg). This difference was not noticeable in hip replacement patients. There was no significant difference in length of stay between the two anesthetic techniques. Discussion: There was no significant difference in the day one pain score between the patients who received a general or spinal anesthetic for either knee or hip replacements. The higher pain scores in the knee replacement group overall are consistent with this being a more painful procedure. This is a small patient population, which means any difference between the two groups is unlikely to be representative of a larger population. The pain scale has 4 points, which means it is difficult to identify a significant difference between pain scores. Conclusion: There is currently little standardization between the different anesthetic approaches utilized in Nevill Hall Hospital. This is likely due to the lack of adherence to a standardized anesthetic regimen. In accordance with ERAS recommends a standard anesthetic protocol is a core component. The results of this study and the guidance from the ERAS society will support the implementation of a new health board wide ERAS protocol.

Keywords: anaesthesia, orthopaedics, intensive care, patient centered decision making, treatment escalation

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Authors: Aaron Liggett

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This research focuses on the visionary proposal made by the Olmsted Brothers Landscape Architecture firm in the 1920s for a network of interconnected parkways in Los Angeles. Their envisioned parkways aimed to address environmental and cultural strains by providing green space for recreation, wildlife habitat, and stormwater management while serving as multimodal transportation routes. Although the parkways were never constructed, through an evidence-based approach, this research presents a framework for evaluating the potential functionality and success of the parkways by modeling and visualizing their quantitative and qualitative landscape performance and benefits. Historical documents and innovative digital modeling tools produce detailed analysis, modeling, and visualization of the parkway designs. A set of 1928 construction documents are used to analyze and interpret the design intent of the parkways. Grading plans are digitized in CAD and modeled in Sketchup to produce 3D visualizations of the parkway. Drainage plans are digitized to model stormwater performance. Planting plans are analyzed to model urban forestry and biodiversity. The EPA's Storm Water Management Model (SWMM) predicts runoff quantity and quality. The USDA Forests Service tools evaluate carbon sequestration and air quality. Spatial and overlay analysis techniques are employed to assess urban connectivity and the spatial impacts of the parkway designs. The study reveals how the integration of blue infrastructure, green infrastructure, and transportation infrastructure within the parkway design creates a multifunctional landscape capable of offering alternative spatial and temporal uses. The analysis demonstrates the potential for multiple functional, ecological, aesthetic, and social benefits to be derived from the proposed parkways. The analysis of the Olmsted Brothers' proposed Los Angeles parkways, which predated contemporary ecological design and resiliency practices, demonstrates the potential for providing multiple functional, ecological, aesthetic, and social benefits within urban designs. The findings highlight the importance of integrated blue, green, and transportation infrastructure in creating a multifunctional landscape that simultaneously serves multiple purposes. The research contributes new methods for modeling and visualizing landscape performance benefits, providing insights and techniques for informing future designs and sustainable development strategies.

Keywords: landscape architecture, ecological urban design, greenway, landscape performance

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Authors: Mojtaba Eshraghi Arani

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The freight forwarders, who are known as the Architect of Transportation, play a vital role in the supply chain management. The package of various services which they provide has made the legal nature of freight forwarders very controversial, so that they might be qualified once as principal or carrier and, on other occasions, as agent of the shipper as the case may be. They could even be involved in the transportation process as the agent of shipping line, which makes the situation much more complicated. The courts in all countries have long had trouble in distinguishing the “forwarder as agent” from “forwarder as principal” (as it is outstanding in the prominent case of “Vastfame Camera Ltd v Birkart Globistics Ltd And Others” 2005, Hong Kong). It is not fully known that in the case of a claim against the forwarder, what particular parameter would be used by the judge among multiple, and sometimes contradictory, tests for determining the scope of the forwarder liability. In particular, every country has its own legal parameters for qualifying the freight forwarders that is completely different from others, as it is the case in France in comparison with Germany and England. The unpredictability of the courts’ decisions in this regard has provided the freight forwarders with the opportunity to impose any limitation or exception of liability while pretending to play the role of a principal, consequently making the cargo interests incur ever-increasing damage. The transportation industry needs to remove such uncertainty by unifying national laws governing freight forwarders liability. A long time ago, in 1967, The International Institute for Unification of Private Law (UNIDROIT) prepared a draft convention called “Draft Convention on Contract of Agency for Forwarding Agents Relating to International Carriage of Goods” (hereinafter called “UNIDROIT draft convention”). The UNIDROIT draft convention provided a clear and certain framework for the liability of freight forwarder in each capacity as agent or carrier, but it failed to transform to a convention, and eventually, it was consigned to oblivion. Today, after nearly 6 decades from that era, the necessity of such convention can be felt apparently. However, one might reason that the same grounds, in particular, the resistance by forwarders’ association, FIATA, exist yet, and thus it is not logical to revive a forgotten draft convention after such long period of time. It is argued in this article that the main reason for resisting the UNIDROIT draft convention in the past was pending efforts for developing the “1980 United Nation Convention on International Multimodal Transport of Goods”. However, the latter convention failed to become in force on due time in a way that there was no new accession since 1996, as a result of which the UNIDROIT draft convention must be revived strongly and immediately submitted to the relevant diplomatic conference. A qualitative method with the concept of interpretation of data collection has been used in this manuscript. The source of the data is the analysis of international conventions and cases.

Keywords: freight forwarder, revival, agent, principal, uidroit, draft convention

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Authors: Rachel S. E. Lim, Winnie L. C. Tan

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Visual literacy is about making meaning through the interaction of images, words, and sounds. Graphic communication students typically develop visual literacy through critique and production of studio-based projects for their portfolios. However, the abrupt switch to online learning during the COVID-19 pandemic has made it necessary to consider new strategies of visualization and planning to scaffold teaching and learning. This study, therefore, investigated how MIRO, a cloud-based visual collaboration platform, could be used to develop the visual literacy confidence of 30 diploma in graphic communication students attending a graphic design course at a Singapore arts institution. Due to COVID-19, the course was taught fully online throughout a 16-week semester. Guided by Kolb’s Experiential Learning Cycle, the two lecturers developed students’ engagement with visual literacy concepts through different activities that facilitated concrete experiences, reflective observation, abstract conceptualization, and active experimentation. Throughout the semester, students create, collaborate, and centralize communication in MIRO with infinite canvas, smart frameworks, a robust set of widgets (i.e., sticky notes, freeform pen, shapes, arrows, smart drawing, emoticons, etc.), and powerful platform capabilities that enable asynchronous and synchronous feedback and interaction. Students then drew upon these multimodal experiences to brainstorm, research, and develop their motion design project. A survey was used to examine students’ perceptions of engagement (E), confidence (C), learning strategies (LS). Using multiple regression, it¬ was found that the use of MIRO helped students develop confidence (C) with visual literacy, which predicted performance score (PS) that was measured against their application of visual literacy to the creation of their motion design project. While students’ learning strategies (LS) with MIRO did not directly predict confidence (C) or performance score (PS), it fostered positive perceptions of engagement (E) which in turn predicted confidence (C). Content analysis of students’ open-ended survey responses about their learning strategies (LS) showed that MIRO provides organization and structure in documenting learning progress, in tandem with establishing standards and expectations as a preparatory ground for generating feedback. With the clarity and sequence of the mentioned conditions set in place, these prerequisites then lead to the next level of personal action for self-reflection, self-directed learning, and time management. The study results show that the affordances of MIRO can develop visual literacy and make up for the potential pitfalls of student isolation, communication, and engagement during online learning. The context of how MIRO could be used by lecturers to orientate students for learning in visual literacy and studio-based projects for future development are discussed.

Keywords: design education, graphic communication, online learning, visual literacy

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Authors: Mary Hanhoun, Jilla Bamarni, Anne-Sophie Bougard

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INSPIR’ECO is a 18-month research and innovation project that aims to specify and develop a tool to offer new services for industrials and territorial planners/managers based on Industrial Ecology Principles. This project is carried out on the territory of Salaise Sablons and the services are designed to be deployed on other territories. Salaise-Sablons area is located in the limit of 5 departments on a major European economic axis multimodal traffic (river, rail and road). The perimeter of 330 ha includes 90 hectares occupied by 20 companies, with a total of 900 jobs, and represents a significant potential basin of development. The project involves five multi-disciplinary partners (Syndicat Mixte INSPIRA, ENGIE, IDEEL, IDEAs Laboratory and TREDI). INSPIR’ECO project is based on the principles that local stakeholders need services to pool, share their activities/equipment/purchases/materials. These services aims to : 1. initiate and promote exchanges between existing companies and 2. identify synergies between pre-existing industries and future companies that could be implemented in INSPIRA. These eco-industrial synergies can be related to: the recovery / exchange of industrial flows (industrial wastewater, waste, by-products, etc.); the pooling of business services (collective waste management, stormwater collection and reuse, transport, etc.); the sharing of equipments (boiler, steam production, wastewater treatment unit, etc.) or resources (splitting jobs cost, etc.); and the creation of new activities (interface activities necessary for by-product recovery, development of products or services from a newly identified resource, etc.). These services are based on IT tool used by the interested local stakeholders that intends to allow local stakeholders to take decisions. Thus, this IT tool: - include an economic and environmental assessment of each implantation or pooling/sharing scenarios for existing or further industries; - is meant for industrial and territorial manager/planners - is designed to be used for each new industrial project. - The specification of the IT tool is made through an agile process all along INSPIR’ECO project fed with: - Users expectations thanks to workshop sessions where mock-up interfaces are displayed; - Data availability based on local and industrial data inventory. These input allow to specify the tool not only with technical and methodological constraints (notably the ones from economic and environmental assessments) but also with data availability and users expectations. A feedback on innovative resource management initiatives in port areas has been realized in the beginning of the project to feed the designing services step.

Keywords: development opportunities, INSPIR’ECO, INSPIRA, industrial ecology, planification, synergy identification

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Authors: E. Calil, L. A. Pereira

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The acquisition of orthography is a complex process, involving both lexical and grammatical questions. This learning occurs simultaneously with the domain of multiple textual aspects (e.g.: graphs, punctuation, etc.). However, most of the research on orthographic acquisition focus on this acquisition from an autonomous point of view, separated from the process of textual production. This means that their object of analysis is the production of words selected by the researcher or the requested sentences in an experimental and controlled setting. In addition, the analysis of the Spelling Problems (SP) are identified by the researcher on the sheet of paper. Considering the perspective of Textual Genetics, from an enunciative approach, this study will discuss the SPs recognized by dyads of newly literate students, while they are writing a text collaboratively. Six proposals of textual production were registered, requested by a 2nd year teacher of a Portuguese Primary School between January and March 2015. In our case study we discuss the SPs recognized by the dyad B and L (7 years old). We adopted as a methodological tool the Ramos System audiovisual record. This system allows real-time capture of the text in process and of the face-to-face dialogue between both students and their teacher, and also captures the body movements and facial expressions of the participants during textual production proposals in the classroom. In these ecological conditions of multimodal registration of collaborative writing, we could identify the emergence of SP in two dimensions: i. In the product (finished text): SP identification without recursive graphic marks (without erasures) and the identification of SPs with erasures, indicating the recognition of SP by the student; ii. In the process (text in progress): identification of comments made by students about recognized SPs. Given this, we’ve analyzed the comments on identified SPs during the text in progress. These comments characterize a type of reformulation referred to as Commented Oral Erasure (COE). The COE has two enunciative forms: Simple Comment (SC) such as ' 'X' is written with 'Y' '; or Unfolded Comment (UC), such as ' 'X' is written with 'Y' because...'. The spelling COE may also occur before or during the SP (Early Spelling Recognition - ESR) or after the SP has been entered (Later Spelling Recognition - LSR). There were 631 words entered in the 6 stories written by the B-L dyad, 145 of them containing some type of SP. During the text in progress, the students recognized orally 174 SP, 46 of which were identified in advance (ESRs) and 128 were identified later (LSPs). If we consider that the 88 erasure SPs in the product indicate some form of SP recognition, we can observe that there were twice as many SPs recognized orally. The ESR was characterized by SC when students asked their colleague or teacher how to spell a given word. The LSR presented predominantly UC, verbalizing meta-orthographic arguments, mostly made by L. These results indicate that writing in dyad is an important didactic strategy for the promotion of metalinguistic reflection, favoring the learning of spelling.

Keywords: collaborative writing, erasure, learning, metalinguistic awareness, spelling, text production

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Authors: Kim Haekyoung, Au Yunkyoung

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As digital technology continues to advance and become more widely accessible, young children are also growing up experiencing various media from infancy. In this changing environment, educating young children on media literacy has become an increasingly important task. With the diversification of media, it has become more necessary for children to understand, utilize, and critically explore the meaning of multimodal texts, which include text, images, and sounds connected to each other. Early childhood is a period when media literacy can bloom, and educational and policy support are needed to enable young children to express their opinions, communicate, and participate fully. However, most current media literacy education for young children focuses solely on teaching how to use media, with limited practical application and utilization. Therefore, this study aims to develop an inquiry-based media literacy education program for young children using topic-specific media content and explore the program's potential and impact on children's media literacy learning. Based on a theoretical and literature review on media literacy education, analysis of existing educational programs, and a survey on the current status and teacher perception of media literacy education for young children, this study developed a media literacy education program for young children considering the components of media literacy (understanding media characteristics, self-regulation, self-expression, critical understanding, ethical norms, social communication). To verify the effectiveness of the program, it was implemented with 20 five-year-old children from C City S Kindergarten, starting from March 24 to May 26, 2022, once a week for a total of 6 sessions. To explore quantitative changes before and after program implementation, repeated-measures analysis of variance was conducted, and qualitative analysis was used to analyze observed changes in the process. significant improvement in media literacy levels, such as understanding media characteristics, self-regulation, self-expression, critical understanding, ethical norms, and social communication. The developed inquiry-based media literacy education program for young children in this study can be effectively applied to enhance children's media literacy education and help improve their media literacy levels. Observed changes in the process also confirmed that children improved their ability to learn various topics, express their thoughts, and communicate with others using media content. These findings emphasize the importance of developing and implementing media literacy education programs and can help children develop the ability to safely and effectively use media in their media environment. Based on exploring the potential and impact of the inquiry-based media literacy education program for young children, this study confirmed positive changes in children's media literacy levels as a result of the program's implementation. These findings suggest that beyond education on how to use media, it can help develop children's ability to safely and effectively use media in their media environment. Furthermore, to improve children's media literacy levels and create a safe media environment, a variety of content and methodologies are needed, and continuous development and evaluation of educational programs are anticipated.

Keywords: young children, media literacy, media literacy education program, media content

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Authors: Alinka Molnár-Tóth, Tímea Tánczos, Regina Barna, Katalin Jakab, Péter Klivényi

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Supported by neuroscientific findings, the so-called Hub-and-Spoke model of the human semantic system is based on two subcomponents of semantic cognition, namely the semantic control process and semantic representation. Our semantic knowledge is multimodal in nature, as the knowledge system stored in relation to a conception is extensive and broad, while different aspects of the conception may be relevant depending on the purpose. The motivation of our research is to develop a new diagnostic measurement procedure based on the preservation of semantic representation, which is appropriate to the specificities of the Hungarian language and which can be used to compare the non-verbal semantic knowledge of healthy and aphasic persons. The development of the test will broaden the Hungarian clinical diagnostic toolkit, which will allow for more specific therapy planning. The sample of healthy persons (n=480) was determined by the last census data for the representativeness of the sample. Based on the concept of the Pyramids and Palm Tree Test, and according to the characteristics of the Hungarian language, we have elaborated a test based on different types of semantic information, in which the subjects are presented with three pictures: they have to choose the one that best fits the target word above from the two lower options, based on the semantic relation defined. We have measured 5 types of semantic knowledge representations: associative relations, taxonomy, motional representations, concrete as well as abstract verbs. As the first step in our data analysis, we examined the normal distribution of our results, and since it was not normally distributed (p < 0.05), we used nonparametric statistics further into the analysis. Using descriptive statistics, we could determine the frequency of the correct and incorrect responses, and with this knowledge, we could later adjust and remove the items of questionable reliability. The reliability was tested using Cronbach’s α, and it can be safely said that all the results were in an acceptable range of reliability (α = 0.6-0.8). We then tested for the potential gender differences using the Mann Whitney-U test, however, we found no difference between the two (p < 0.05). Likewise, we didn’t see that the age had any effect on the results using one-way ANOVA (p < 0.05), however, the level of education did influence the results (p > 0.05). The relationships between the subtests were observed by the nonparametric Spearman’s rho correlation matrix, showing statistically significant correlation between the subtests (p > 0.05), signifying a linear relationship between the measured semantic functions. A margin of error of 5% was used in all cases. The research will contribute to the expansion of the clinical diagnostic toolkit and will be relevant for the individualised therapeutic design of treatment procedures. The use of a non-verbal test procedure will allow an early assessment of the most severe language conditions, which is a priority in the differential diagnosis. The measurement of reaction time is expected to advance prodrome research, as the tests can be easily conducted in the subclinical phase.

Keywords: communication disorders, diagnostic toolkit, neurorehabilitation, semantic knowlegde

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Authors: Marcel Schulze, Behrem Aslan, Silke Lux, Alexandra Philipsen

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Objective: Patients with Attention Deficit/Hyperactivity Disorder (ADHD) often report that they are being flooded by sensory impressions. Studies investigating sensory processing show hypersensitivity for sensory inputs across the senses in children and adults with ADHD. Especially the auditory modality is affected by deficient acoustical inhibition and modulation of signals. While studying unimodal signal-processing is relevant and well-suited in a controlled laboratory environment, everyday life situations occur multimodal. A complex interplay of the senses is necessary to form a unified percept. In order to achieve this, the unimodal sensory modalities are bound together in a process called multisensory integration (MI). In the current study we investigate MI in an adult ADHD sample using the McGurk-effect – a well-known illusion where incongruent speech like phonemes lead in case of successful integration to a new perceived phoneme via late top-down attentional allocation . In ADHD neuronal dysregulation at rest e.g., aberrant within or between network functional connectivity may also account for difficulties in integrating across the senses. Therefore, the current study includes resting-state functional connectivity to investigate a possible relation of deficient network connectivity and the ability of stimulus integration. Method: Twenty-five ADHD patients (6 females, age: 30.08 (SD:9,3) years) and twenty-four healthy controls (9 females; age: 26.88 (SD: 6.3) years) were recruited. MI was examined using the McGurk effect, where - in case of successful MI - incongruent speech-like phonemes between visual and auditory modality are leading to a perception of a new phoneme. Mann-Whitney-U test was applied to assess statistical differences between groups. Echo-planar imaging-resting-state functional MRI was acquired on a 3.0 Tesla Siemens Magnetom MR scanner. A seed-to-voxel analysis was realized using the CONN toolbox. Results: Susceptibility to McGurk was significantly lowered for ADHD patients (ADHDMdn:5.83%, ControlsMdn:44.2%, U= 160.5, p=0.022, r=-0.34). When ADHD patients integrated phonemes, reaction times were significantly longer (ADHDMdn:1260ms, ControlsMdn:582ms, U=41.0, p<.000, r= -0.56). In functional connectivity medio temporal gyrus (seed) was negatively associated with primary auditory cortex, inferior frontal gyrus, precentral gyrus, and fusiform gyrus. Conclusion: MI seems to be deficient for ADHD patients for stimuli that need top-down attentional allocation. This finding is supported by stronger functional connectivity from unimodal sensory areas to polymodal, MI convergence zones for complex stimuli in ADHD patients.

Keywords: attention-deficit hyperactivity disorder, audiovisual integration, McGurk-effect, resting-state functional connectivity

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Authors: Robert E. Kenney, Richard B. Aguilar, Efrain Antunez, Gregory Schor-Haskin, Rafael Rey, Catie Falcon, Luis Arce

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This study sought to explore the effect of Sarapin injections on chronic knee pain (CKP). Many adults suffer from CKP which is most often attributed to osteoarthritis. Current treatment regimens for CKP involve the use NSAIDS medications, injections with steroids/analgesic, platelet rich plasma injections, or orthopedic surgical interventions. Sarapin is a commercially available homeopathic aqueous extract from the pitcher plant. Studies on the use of Sarapin as a treatment for cervical, thoracic, and lumbosacral facet joint nerve blocks have been performed with mixed results. There is little available evidence on the use of Sarapin in CKP. This study examines the effect of a series of 3 weekly injections of aqueous Sarapin in 95 elderly patients with CKP in a primary care setting. Cano Health, a primary care group, identified 95 successive patients with CKP from its multimodal physiotherapy program for chronic pain. Patients underwent evaluation by a clinician, underwent diagnostic Xrays of the knees, and the treatment plan with three weekly Sarapin injections was discussed. A pain and functional limitation survey (a modified Lower Extremity Functional Scale (mLEFS)) was administered prior to initiating treatment (Entry Survey (ES)). Each patient received an intraarticular injection of 2 cc of aqueous Sarapin with 1cc 1% lidocaine during weeks 1, 2 and 3. The mLEFS was administered again at week 4, one week after the third Sarapin injection (Exit Survey (ExS)). Demographics: Mean Age 62 +/- 9.8; 73% female; 89% Hispanic/Latino; mean time between ES and ExS was 27.5 +/-8.2 days. Survey: The mLEFS was based on a published Lower Extremity Functional Scale and each patient rated their pain or functional limitation from 0 (no difficulty) to 5 (severe difficulty) for 10 questions. Answers were summed and compared. Maximum score for severe difficulty would be 50 points. Results: Mean pain/functional scores: ES was 30.3 +/-12.1 and ExS was 19.5 +/- 12.5. This represents a relative improvement of 35.7% (P<0.00001). A total of 81% (77/95) of the patients showed improvement in symptoms at week four as assessed by the mLEFS. There were 11 patients who reported an increase in their survey scores while 7 patients reported no change. When evaluating the cohort that reported improvement, the ES was 30.9 +/-11.4 and ExS was 16.3 +/-9.8 yielding a 47.2% relative improvement (P<0.00001). Injections were well tolerated, and no adverse events were reported. Conclusions: In this cohort of 95 elderly patients with CKP, treatment with 3 weekly injections of Sarapin significantly improved pain and function as assessed by a mLEFS survey. The majority (81%) of patients responded positively to therapy, 12% had worsening symptoms and 7% reported no change. The use of intraarticular injections of Sarapin for CKP was shown to be an effective modality of treatment. Sarapin’s low cost, tolerability, and ease of use make it an attractive alternative to NSAIDS, steroids, PRP or surgical intervention for this common debilitating condition.

Keywords: Sarapin, intraarticular, chronic knee pain, osteoarthritis

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Authors: Eleni Maistrou, D. Kosmopoulos, Carolina Moretti, Amalia Konidi, Katerina Boulougoura

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InterArch is an ongoing research project that has been running since September 2020. It aims to propose the design of a site-based digital application for archaeological sites and outdoor guided tours, supporting virtual and augmented reality technology. The research project is co‐financed by the European Union and Greek national funds, through the Operational Program Competitiveness, Entrepreneurship, and Innovation, under the call RESEARCH - CREATE – INNOVATE (project code: Τ2ΕΔΚ-01659). It involves mutual collaboration between academic and cultural institutions and the contribution of an IT applications development company. The research will be completed by July 2023 and will run as a pilot project for the city of Ancient Messene, a place of outstanding natural beauty in the west of Peloponnese, which is considered one of the most important archaeological sites in Greece. The applied research project integrates an interactive approach to the natural environment, aiming at a manifold sensory experience. It combines the physical space of the archaeological site with the digital space of archaeological and cultural data while at the same time, it embraces storytelling processes by engaging an interdisciplinary approach that familiarizes the user with multiple semantic interpretations. The mingling of the real-world environment with its digital and cultural components by using augmented reality techniques could potentially transform the visit on-site into an immersive multimodal sensory experience. To this purpose, an extensive spatial analysis along with a detailed evaluation of the existing digital and non-digital archives is proposed in our project, intending to correlate natural landscape morphology (including archaeological material remains and environmental characteristics) with the extensive historical records and cultural digital data. On-site research was carried out, during which visitors’ itineraries were monitored and tracked throughout the archaeological visit using GPS locators. The results provide our project with useful insight concerning the way visitors engage and interact with their surroundings, depending on the sequence of their itineraries and the duration of stay at each location. InterArch aims to propose the design of a site-based digital application for archaeological sites and outdoor guided tours, supporting virtual and augmented reality technology. Extensive spatial analysis, along with a detailed evaluation of the existing digital and non-digital archives, is used in our project, intending to correlate natural landscape morphology with the extensive historical records and cultural digital data. The results of the on-site research provide our project with useful insight concerning the way visitors engage and interact with their surroundings, depending on the sequence of their itineraries and the duration of stay at each location.

Keywords: archaeological site, digital space, semantic interpretations, cultural heritage

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Authors: Shang Yee Chong

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Perioperative pain is a complex mechanism activated by various nociceptive, neuropathic, and inflammatory pathways. Opioids have long been a mainstay for analgesia in this period, even as we are continuously moving towards a multimodal model to improve pain control while minimising side effects. Dexmedetomidine, a potent alpha-2 agonist, is a useful sedative and hypnotic agent. Its use in the intensive care unit has been well described, and it is increasingly an adjunct intraoperatively for its opioid sparing effects and to decrease pain scores. We describe a case of a general surgical patient in whom minimal opioids was required with dexmedetomidine use. The patient was a 61-year-old Indian gentleman with a history of hyperlipidaemia and type 2 diabetes mellitus, presenting with rectal adenocarcinoma detected on colonoscopy. He was scheduled for a robotic ultra-low anterior resection. The patient was induced with intravenous fentanyl 75mcg, propofol 160mg and atracurium 40mg. He was intubated conventionally and mechanically ventilated. Anaesthesia was maintained with inhalational desflurane and anaesthetic depth was measured with the Masimo EEG Sedline brain function monitor. An initial intravenous dexmedetomidine dose (bolus) of 1ug/kg for 10 minutes was given prior to anaesthetic induction and thereafter, an infusion of 0.2-0.4ug/kg/hr to the end of surgery. In addition, a bolus dose of intravenous lignocaine 1.5mg/kg followed by an infusion at 1mg/kg/hr throughout the surgery was administered. A total of 10mmol of magnesium sulphate and intravenous paracetamol 1000mg were also given for analgesia. There were no significant episodes of bradycardia or hypotension. A total of intravenous phenylephrine 650mcg was given throughout to maintain the patient’s mean arterial pressure within 10-15mmHg of baseline. The surgical time lasted for 5 hours and 40minutes. Postoperatively the patient was reversed and extubated successfully. He was alert and comfortable and pain scores were minimal in the immediate post op period in the postoperative recovery unit. Time to first analgesia was 4 hours postoperatively – with paracetamol 1g administered. This was given at 6 hourly intervals strictly for 5 days post surgery, along with celecoxib 200mg BD as prescribed by the surgeon regardless of pain scores. Oral oxycodone was prescribed as a rescue analgesic for pain scores > 3/10, but the patient did not require any dose. Neither was there nausea or vomiting. The patient was discharged on postoperative day 5. This case has reinforced the use of dexmedetomidine as an adjunct in general surgery cases, highlighting its excellent opioid-sparing effects. In the entire patient’s hospital stay, the only dose of opioid he received was 75mcg of fentanyl at the time of anaesthetic induction. The patient suffered no opioid adverse effects such as nausea, vomiting or postoperative ileus, and pain scores varied from 0-2/10. However, intravenous lignocaine infusion was also used in this instance, which would have helped improve pain scores. Paracetamol, lignocaine, and dexmedetomidine is thus an effective, opioid-sparing combination of multi-modal analgesia for major abdominal surgery cases.

Keywords: analgesia, dexmedetomidine, general surgery, opioid sparing

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Authors: Tarek Saadawi, Rosario Gennaro, Jonathan Akeley

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There is rapidly growing demand for professionals to fill positions in Cybersecurity. This is recognized as a national priority both by government agencies and the private sector. Cybersecurity is a very wide technical area which encompasses all measures that can be taken in an electronic system to prevent criminal or unauthorized use of data and resources. This requires defending computers, servers, networks, and their users from any kind of malicious attacks. The need to address this challenge has been recognized globally but is particularly acute in the New York metropolitan area, home to some of the largest financial institutions in the world, which are prime targets of cyberattacks. In New York State alone, there are currently around 57,000 jobs in the Cybersecurity industry, with more than 23,000 unfilled positions. The Cybersecurity Program at City College is a collaboration between the Departments of Computer Science and Electrical Engineering. In Fall 2020, The City College of New York matriculated its first students in theCybersecurity Master of Science program. The program was designed to fill gaps in the previous offerings and evolved out ofan established partnership with Facebook on Cybersecurity Education. City College has designed a program where courses, curricula, syllabi, materials, labs, etc., are developed in cooperation and coordination with industry whenever possible, ensuring that students graduating from the program will have the necessary background to seamlessly segue into industry jobs. The Cybersecurity Program has created multiple pathways for prospective students to obtain the necessary prerequisites to apply in order to build a more diverse student population. The program can also be pursued on a part-time basis which makes it available to working professionals. Since City College’s Cybersecurity M.S. program was established to equip students with the advanced technical skills needed to thrive in a high-demand, rapidly-evolving field, it incorporates a range of pedagogical formats. From its outset, the Cybersecurity program has sought to provide both the theoretical foundations necessary for meaningful work in the field along with labs and applied learning projects aligned with skillsets required by industry. The efforts have involved collaboration with outside organizations and with visiting professors designing new courses on topics such as Adversarial AI, Data Privacy, Secure Cloud Computing, and blockchain. Although the program was initially designed with a single asynchronous course in the curriculum with the rest of the classes designed to be offered in-person, the advent of the COVID-19 pandemic necessitated a move to fullyonline learning. The shift to online learning has provided lessons for future development by providing examples of some inherent advantages to the medium in addition to its drawbacks. This talk will address the structure of the newly-implemented Cybersecurity Master’s Program and discuss the innovations, challenges, and possible future directions.

Keywords: cybersecurity, new york, city college, graduate degree, master of science

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Authors: Animesh Pan, Geoffrey D. Bothun

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With the development of nanotechnology, research in multifunctional delivery systems has a new pace and dimension. An incipient challenge is to design an all-in-one delivery system that can be used for multiple purposes, including tumor targeting therapy, radio-frequency (RF-), near-infrared (NIR-), light-, or pH-induced controlled release, photothermal therapy (PTT), photodynamic therapy (PDT), and medical diagnosis. In this regard, various inorganic nanoparticles (NPs) are known to show great potential as the 'functional components' because of their fascinating and tunable physicochemical properties and the possibility of multiple theranostic modalities from individual NPs. Magnetic, luminescent, and plasmonic properties are the three most extensively studied and, more importantly biomedically exploitable properties of inorganic NPs. Although successful attempts of combining any two of them above mentioned functionalities have been made, integrating them in one system has remained challenge. Keeping those in mind, controlled designs of complex colloidal nanoparticle system are one of the most significant challenges in nanoscience and nanotechnology. Therefore, systematic and planned studies providing better revelation are demanded. We report a multifunctional delivery platform-based liposome loaded with drug, iron-oxide magnetic nanoparticles (MNPs), and a gold shell on the surface of liposomes, were synthesized using a lipid with polyelectrolyte (layersomes) templating technique. MNPs and the anti-cancer drug doxorubicin (DOX) were co-encapsulated inside liposomes composed by zwitterionic phophatidylcholine and anionic phosphatidylglycerol using reverse phase evaporation (REV) method. The liposomes were coated with positively charge polyelectrolyte (poly-L-lysine) to enrich the interface with gold anion, exposed to a reducing agent to form a gold nanoshell, and then capped with thio-terminated polyethylene glycol (SH-PEG2000). The core-shell nanostructures were characterized by different techniques like; UV-Vis/NIR scanning spectrophotometer, dynamic light scattering (DLS), transmission electron microscope (TEM). This multifunctional system achieves a variety of functions, such as radiofrequency (RF)-triggered release, chemo-hyperthermia, and NIR laser-triggered for photothermal therapy. Herein, we highlight some of the remaining major design challenges in combination with preliminary studies assessing therapeutic objectives. We demonstrate an efficient loading and delivery system to significant cell death of human cancer cells (A549) with therapeutic capabilities. Coupled with RF and NIR excitation to the doxorubicin-loaded core-shell nanostructure helped in securing targeted and controlled drug release to the cancer cells. The present core-shell multifunctional system with their multimodal imaging and therapeutic capabilities would be eminent candidates for cancer theranostics.

Keywords: cancer thernostics, multifunctional nanostructure, photothermal therapy, radiofrequency targeting

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Authors: Tamar Trop

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Bike sharing systems can be important elements of smart cities as they have the potential for impact on multiple levels. These systems can add a significant alternative to other modes of mass transit in cities that are continuously looking for measures to become more livable and maintain their attractiveness for citizens, businesses and tourism. Bike-sharing began in Europe in 1965, and a viable format emerged in the mid-2000s thanks to the introduction of information technology. The rate of growth in bike-sharing schemes and fleets has been very rapid since 2008 and has probably outstripped growth in every other form of urban transport. Today, public bike-sharing systems are available on five continents, including over 700 cities, operating more than 800,000 bicycles at approximately 40,000 docking stations. Since modern bike sharing systems have become prevalent only in the last decade, the existing literature analyzing these systems and their sustainability is relatively new. The purpose of the presented study is to assess the sustainability of these newly emerging transportation systems, by using the Envision™ rating system as a methodological framework and the Israeli 'Tel -O-Fun' – bike sharing project as a case study. The assessment was conducted by project team members. Envision™ is a new guidance and rating system used to assess and improve the sustainability of all types and sizes of infrastructure projects. This tool provides a holistic framework for evaluating and rating the community, environmental, and economic benefits of infrastructure projects over the course of their life cycle. This evaluation method has 60 sustainability criteria divided into five categories: Quality of life, leadership, resource allocation, natural world, and climate and risk. 'Tel -O-Fun' project was launched in Tel Aviv-Yafo on 2011 and today provides about 1,800 bikes for rent, at 180 rental stations across the city. The system is based on a complex computer terminal that is located in the docking stations. The highest-rated sustainable features that the project scored include: (a) Improving quality of life by: offering a low cost and efficient form of public transit, improving community mobility and access, enabling the flexibility of travel within a multimodal transportation system, saving commuters time and money, enhancing public health and reducing air and noise pollution; (b) improving resource allocation by: offering inexpensive and flexible last-mile connectivity, reducing space, materials and energy consumption, reducing wear and tear on public roads, and maximizing the utility of existing infrastructure, and (c) reducing of greenhouse gas emissions from transportation. Overall, 'Tel -O-Fun' project was highly scored as an environmentally sustainable and socially equitable infrastructure. The use of this practical framework for evaluation also yielded various interesting insights on the shortcoming of the system and the characteristics of good solutions. This can contribute to the improvement of the project and may assist planners and operators of bike sharing systems to develop a sustainable, efficient and reliable transportation infrastructure within smart cities.

Keywords: bike sharing, Envision™, sustainability rating system, sustainable infrastructure

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Authors: Shelley Jones

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Assumptions abound that education for girls will, as a matter of course, lead to their economic empowerment as women; yet. little is known about the ways in which schooling for girls, who traditionally/historically would not have had opportunities for post-primary, or perhaps even primary education – such as the participants in this study based in rural Uganda - in reality, impacts their economic situations. There is a need forlongitudinal studies in which women share experiences, understandings, and reflections of their lives that can inform our knowledge of this. In response, this paper reports on stage four of a longitudinal case study (2004-2018) focused on education and empowerment for girls and women in rural Uganda, in which 13 of the 15 participants from the original study participated. This paper understands empowerment as not simply increased opportunities (e.g., employment) but also real gains in power, freedoms that enable agentive action, and authentic and viable choices/alternatives that offer ‘exit options’ from unsatisfactory situations. As with the other stages, this study used a critical, postmodernist, global feminist ethnographic methodology, multimodal and qualitative data collection. Participants participated in interviews, focus group discussions, and a two-day workshop, which explored their understandings of how/if they understood post-primary education to have contributed to their economic empowerment. A constructivist grounded theory approach was used for data analysis to capture major themes. Findings indicate that although all participants believe that post-primary education provided them with economic opportunities they would not have had otherwise, the parameters of their economic empowerment were severely constrained by historic and extant sociocultural, economic, political, and institutional structures that continue to disempower girls and women, as well as additional financial responsibilities that they assumed to support others. Even though the participants had post-primary education, and they were able to obtain employment or operate their own businesses that they would not likely have been able to do without post-primary education, the majority of the participants’ incomes were not sufficient to elevate them financially above the extreme poverty level, especially as many were single mothers and the sole income earners in their households. Furthermore, most deemed their working conditions unsatisfactory and their positions precarious; they also experienced sexual harassment and abuse in the labour force. Additionally, employment for the participants resulted in a double work burden: long days at work, surrounded by many hours of domestic work at home (which, even if they had spousal partners, still fell almost exclusively to women). In conclusion, although the participants seem to have experienced some increase in economic empowerment, largely due to skills, knowledge, and qualifications gained at the post-primary level, numerous barriers prevented them from maximizing their capabilities and making significant gains in empowerment. There is need, in addition to providing education (primary, secondary, and tertiary) to girls, to address systemic gender inequalities that mitigate against women’s empowerment, as well as opportunities and freedom for women to come together and demand fair pay, reasonable working conditions, and benefits, freedom from gender-based harassment and assault in the workplace, as well as advocate for equal distribution of domestic work as a cultural change.

Keywords: girls' post-primary education, women's empowerment, uganda, employment

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Authors: L. J. de Jager

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In the South African English school curriculum, one of the aims is to achieve communicative competence, the knowledge of using language competently and appropriately in a speech community. Communicatively competent speakers should not only produce grammatically correct sentences but also produce contextually appropriate sentences for various purposes and in different situations. As most speakers of English are non-native speakers, achieving communicative competence remains a complex challenge. Moreover, the changing needs of society necessitate not merely language proficiency, but also technological proficiency. One of the burning issues in the South African educational landscape is the replacement of the standardised literacy model by the pedagogy of multiliteracies that incorporate, by default, the exploration of technological text forms that are part of learners’ everyday lives. It foresees learners as decoders, encoders, and manufacturers of their own futures by exploiting technological possibilities to constantly create and recreate meaning. As such, 21st century learners will feel comfortable working with multimodal texts that are intrinsically part of their lives and by doing so, become authors of their own learning experiences while teachers may become agents supporting learners to discover their capacity to acquire new digital skills for the century of multiliteracies. The aim is transformed practice where learners use their skills, ideas, and knowledge in new contexts. This paper reports on a research project on the integration of technology for language learning, based on the technological pedagogical content knowledge framework, conceptually founded in the theory of multiliteracies, and which aims to achieve communicative competence. The qualitative study uses the community of inquiry framework to answer the research question: How does the integration of technology transform language teaching of preservice teachers? Pre-service teachers in the Postgraduate Certificate of Education Programme with English as methodology were purposively selected to source and evaluate apps for teaching and learning English. The participants collaborated online in a dedicated Blackboard module, using discussion threads to sift through applicable apps and develop interactive lessons using the Apps. The selected apps were entered on to a predesigned Qualtrics form. Data from the online discussions, focus group interviews, and reflective journals were thematically and inductively analysed to determine the participants’ perceptions and experiences when integrating technology in lesson design and the extent to which communicative competence was achieved when using these apps. Findings indicate transformed practice among participants and research team members alike with a better than average technology acceptance and integration. Participants found value in online collaboration to develop and improve their own teaching practice by experiencing directly the benefits of integrating e-learning into the teaching of languages. It could not, however, be clearly determined whether communicative competence was improved. The findings of the project may potentially inform future e-learning activities, thus supporting student learning and development in follow-up cycles of the project.

Keywords: apps, communicative competence, English teaching, technology integration, technological pedagogical content knowledge

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Authors: Aditya Purohit, Neha Bansal

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Unplanned urbanization and multidirectional sprawl of the cities have resulted in increased motorization and deteriorating transport conditions like traffic congestion, longer commuting, pollution, increased carbon footprint, and above all increased fatalities. In order to overcome these problems, various practices have been adopted including– promoting and implementing mass transport; traffic junction channelization; smart transport etc. However, these methods are found to be primarily focusing on vehicular mobility rather than people accessibility. With this research gap, this paper tries to resolve the mobility issues for Ahmedabad city in India, which being the economic capital Gujarat state has a huge commuter and visitor inflow. This research aims to resolve the traffic congestion and urban mobility issues focusing on Gujarat State Regional Transport Corporation (GSRTC) for the city of Ahmadabad by analyzing the existing operations and network structure of GSRTC followed by finding possibilities of integrating it with other modes of urban transport. The network restructuring (NR) methodology is used with appropriate variations, based on commuter demand and growth pattern of the city. To do these ‘scenarios’ based on priority issues (using 12 parameters) and their best possible solution, are established after route network analysis for 2700 population sample of 20 traffic junctions/nodes across the city. Approximately 5% sample (of passenger inflow) at each node is considered using random stratified sampling technique two scenarios are – Scenario 1: Resolving mobility issues by use of Special Purpose Vehicle (SPV) in joint venture to GSRTC and Private Operators for establishing feeder service, which shall provide a transfer service for passenger for movement from inner city area to identified peripheral terminals; and Scenario 2: Augmenting existing mass transport services such as BRTS and AMTS for using them as feeder service to the identified peripheral terminals. Each of these has now been analyzed for the best suitability/feasibility in network restructuring. A desire-line diagram is constructed using this analysis which indicated that on an average 62% of designated GSRTC routes are overlapping with mass transportation service routes of BRTS and AMTS in the city. This has resulted in duplication of bus services causing traffic congestion especially in the Central Bus Station (CBS). Terminating GSRTC services on the periphery of the city is found to be the best restructuring network proposal. This limits the GSRTC buses at city fringe area and prevents them from entering into the city core areas. These end-terminals of GSRTC are integrated with BRTS and AMTS services which help in segregating intra-state and inter-state bus services. The research concludes that absence of integrated multimodal transport network resulted in complexity of transport access to the commuters. As a further scope of research comparing and understanding of value of access time in total travel time and its implication on generalized cost on trip and how it varies city wise may be taken up.

Keywords: mass transportation, multi-modal integration, network restructuring, travel behavior, urban transport

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Authors: John Doe

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This paper presents the research project “Escape Through Culture”, which is co-funded by the European Union and national resources through the Operational Programme “Competitiveness, Entrepreneurship and Innovation” 2014-2020 and the Single RTDI State Aid Action "RESEARCH - CREATE - INNOVATE". The project implementation is assumed by three partners, (1) the Computer Technology Institute and Press "Diophantus" (CTI), experienced with the design and implementation of serious games, natural language processing and ICT in education, (2) the Laboratory of Environmental Communication and Audiovisual Documentation (LECAD), part of the University of Thessaly, Department of Architecture, which is experienced with the study of creative transformation and reframing of the urban and environmental multimodal experiences through the use of AR and VR technologies, and (3) “Apoplou”, an IT Company with experience in the implementation of interactive digital applications. The research project proposes the design of innovative infrastructure of digital educational escape games for mobile devices and computers, with the use of Virtual Reality and Augmented Reality for the promotion of Greek cultural heritage in Greece and abroad. In particular, the project advocates the combination of Greek cultural heritage and literature, digital technologies advancements and the implementation of innovative gamifying practices. The cultural experience of the players will take place in 3 layers: (1) In space: the digital games produced are going to utilize the dual character of the space as a cultural landscape (the real space - landscape but also the space - landscape as presented with the technologies of augmented reality and virtual reality). (2) In literary texts: the selected texts of Greek writers will support the sense of place and the multi-sensory involvement of the user, through the context of space-time, language and cultural characteristics. (3) In the philosophy of the "escape game" tool: whether played in a computer environment, indoors or outdoors, the spatial experience is one of the key components of escape games. The innovation of the project lies both in the junction of Augmented/Virtual Reality with the promotion of cultural points of interest, as well as in the interactive, gamified practices of literary texts. The digital escape game infrastructure will be highly interactive, integrating the projection of Greek landscape cultural elements and digital literary text analysis, supporting the creation of escape games, establishing and highlighting new playful ways of experiencing iconic cultural places, such as Elefsina, Skiathos etc. The literary texts’ content will relate to specific elements of the Greek cultural heritage depicted by prominent Greek writers and poets. The majority of the texts will originate from Greek educational content available in digital libraries and repositories developed and maintained by CTI. The escape games produced will be available for use during educational field trips, thematic tourism holidays, etc. In this paper, the methodology adopted for infrastructure development will be presented. The research is based on theories of place, gamification, gaming development, making use of corpus linguistics concepts and digital humanities practices for the compilation and the analysis of literary texts.

Keywords: escape games, cultural landscapes, gamification, digital humanities, literature

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Authors: Roberta Mugellesi Dow

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As the climate crisis becomes unignorable, it is imperative that new services are developed addressing not only the needs of customers but also taking into account its impact on the environment. The Telecommunication and Integrated Application (TIA) Directorate of ESA is supporting the green transition with particular attention to the sustainable mobility.“Accelerating the shift to sustainable and smart mobility” is at the core of the European Green Deal strategy, which seeks a 90% reduction in related emissions by 2050 . Transforming the way that people and goods move is essential to increasing mobility while decreasing environmental impact, and transport must be considered holistically to produce a shared vision of green intermodal mobility. The use of space technologies, integrated with terrestrial technologies, is an enabler of smarter traffic management and increased transport efficiency for automated and connected multimodal mobility. Satellite connectivity, including future 5G networks, and digital technologies such as Digital Twin, AI, Machine Learning, and cloud-based applications are key enablers of sustainable mobility.SatCom is essential to ensure that connectivity is ubiquitously available, even in remote and rural areas, or in case of a failure, by the convergence of terrestrial and SatCom connectivity networks, This is especially crucial when there are risks of network failures or cyber-attacks targeting terrestrial communication. SatCom ensures communication network robustness and resilience. The combination of terrestrial and satellite communication networks is making possible intelligent and ubiquitous V2X systems and PNT services with significantly enhanced reliability and security, hyper-fast wireless access, as well as much seamless communication coverage. SatNav is essential in providing accurate tracking and tracing capabilities for automated vehicles and in guiding them to target locations. SatNav can also enable location-based services like car sharing applications, parking assistance, and fare payment. In addition to GNSS receivers, wireless connections, radar, lidar, and other installed sensors can enable automated vehicles to monitor surroundings, to ‘talk to each other’ and with infrastructure in real-time, and to respond to changes instantaneously. SatEO can be used to provide the maps required by the traffic management, as well as evaluate the conditions on the ground, assess changes and provide key data for monitoring and forecasting air pollution and other important parameters. Earth Observation derived data are used to provide meteorological information such as wind speed and direction, humidity, and others that must be considered into models contributing to traffic management services. The paper will provide examples of services and applications that have been developed aiming to identify innovative solutions and new business models that are allowed by new digital technologies engaging space and non space ecosystem together to deliver value and providing innovative, greener solutions in the mobility sector. Examples include Connected Autonomous Vehicles, electric vehicles, green logistics, and others. For the technologies relevant are the hybrid satcom and 5G providing ubiquitous coverage, IoT integration with non space technologies, as well as navigation, PNT technology, and other space data.

Keywords: sustainability, connectivity, mobility, satellites

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Authors: Prajna Paramita Naik, Sujit Kumar Bhutia

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Background: Regardless of the development multimodal treatment strategies, oral squamous cell carcinoma (OSCC) is often associated with a high rate of recurrence, metastasis and chemo- and radio- resistance. The present study inspected the relevance of CD44, ABCB1 and ADAM17 expression as a putative stem cell compartment in oral squamous cell carcinoma (OSCC) and deciphered the role of autophagy in regulating the expression of aforementioned proteins, stemness and chemoresistance. Methods: A retrospective analysis of CD44, ABCB1 and ADAM17 expression with respect to the various clinicopathological factors of sixty OSCC patients were determined via immunohistochemistry. The correlation among CD44, ABCB1 and ADAM17 expression was established. Sphere formation assay, flow cytometry and fluorescence microscopy were conducted to elucidate the stemness and chemoresistance nature of established cisplatin-resistant oral cancer cells (FaDu). The pattern of expression of CD44, ABCB1 and ADAM17 in parental (FaDu-P) and resistant FaDu cells (FaDu-CDDP-R) were investigated through fluorescence microscopy. Western blot analysis of autophagy marker proteins was performed to compare the status of autophagy in parental and resistant FaDu cell. To investigate the role of autophagy in chemoresistance and stemness, sphere formation assay, immunofluorescence and Western blot analysis was performed post transfection with siATG14 and the level of expression of autophagic proteins, mitochondrial protein and stemness-associated proteins were analyzed. The statistical analysis was performed by GraphPad Prism 4.0 software. p-value was defined as follows: not significant (n.s.): p > 0.05;*: p ≤ 0.05; **: p ≤ 0.01; ***: p ≤ 0.001; ****: p ≤ 0.0001 were considered statistically significant. Results: In OSCC, high CD44, ABCB1 and ADAM17 expression were significantly correlated with higher tumor grades and poor differentiation. However, the expression of these proteins was not related to the age and sex of OSCC patients. Moreover, the expression of CD44, ABCB1 and ADAM17 were positively correlated with each other. In vitro and OSCC tissue double labeling experiment data showed that CD44+ cells were highly associated with ABCB1 and ADAM17 expression. Further, FaDu-CDDP-R cells showed higher sphere forming capacity along with increased fraction of the CD44+ population and β-catenin expression FaDu-CDDP-R cells also showed accelerated expression of CD44, ABCB1 and ADAM17. A comparatively higher autophagic flux was observed in FaDu-CDDP-R against FaDu-P cells. The expression of mitochondrial proteins was noticeably reduced in resistant cells as compared to parental cells indicating the occurrence of autophagy-mediated mitochondrial degradation in oral cancer. Moreover, inhibition of autophagy was coupled with the decreased formation of orospheres suggesting autophagy-mediated stemness in oral cancer. Blockade of autophagy was also found to induce the restoration of mitochondrial proteins in FaDu-CDDP-R cells indicating the involvement of mitophagy in chemoresistance. Furthermore, a reduced expression of CD44, ABCB1 and ADAM17 was also observed in ATG14 deficient cells FaDu-P and FaDu-CDDP-R cells. Conclusion: The CD44+ ⁄ABCB1+ ⁄ADAM17+ expression in OSCC might be associated with chemoresistance and a putative CSC compartment. Further, the present study highlights the contribution of mitophagy in chemoresistance and confirms the potential involvement of autophagic regulation in acquisition of stem-like characteristics in OSCC.

Keywords: ABCB1, ADAM17, autophagy, CD44, chemoresistance, mitophagy, OSCC, stemness

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Authors: Aleksandra Bylinska, Samantha Slight-Webb, Kevin Thomas, Miles Smith, Susan Macwana, Nicolas Dominguez, Eliza Chakravarty, Joan T. Merrill, Judith A. James, Joel M. Guthridge

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Background: Systemic Lupus Erythematosus (SLE) is an interferon-related autoimmune disease characterized by B cell dysfunction. One of the main hallmarks is a loss of tolerance to self-antigens leading to increased levels of autoantibodies against nuclear components (ANAs). However, up to 20% of healthy ANA+ individuals will not develop clinical illness. SLE is more prevalent among women and minority populations (African, Asian American and Hispanics). Moreover, African Americans have a stronger interferon (IFN) signature and develop more severe symptoms. The exact mechanisms involved in ethnicity-dependent B cell dysregulation and the progression of autoimmune disease from ANA+ healthy individuals to clinical disease remains unclear. Methods: Peripheral blood mononuclear cells (PBMCs) from African (AA) and European American (EA) ANA- (n=12), ANA+ (n=12) and SLE (n=12) individuals were assessed by multimodal scRNA-Seq/CITE-Seq methods to examine differential gene signatures in specific B cell subsets. Library preparation was done with a 10X Genomics Chromium according to established protocols and sequenced on Illumina NextSeq. The data were further analyzed for distinct cluster identification and differential gene signatures in the Seurat package in R and pathways analysis was performed using Ingenuity Pathways Analysis (IPA). Results: Comparing all subjects, 14 distinct B cell clusters were identified using a community detection algorithm and visualized with Uniform Manifold Approximation Projection (UMAP). The proportion of each of those clusters varied by disease status and ethnicity. Transitional B cells trended higher in ANA+ healthy individuals, especially in AA. Ribonucleoprotein high population (HNRNPH1 elevated, heterogeneous nuclear ribonucleoprotein, RNP-Hi) of proliferating Naïve B cells were more prevalent in SLE patients, specifically in EA. Interferon-induced protein high population (IFIT-Hi) of Naive B cells are increased in EA ANA- individuals. The proportion of memory B cells and plasma cells clusters tend to be expanded in SLE patients. As anticipated, we observed a higher signature of cytokine-related pathways, especially interferon, in SLE individuals. Pathway analysis among AA individuals revealed an NRF2-mediated Oxidative Stress response signature in the transitional B cell cluster, not seen in EA individuals. TNFR1/2 and Sirtuin Signaling pathway genes were higher in AA IFIT-Hi Naive B cells, whereas they were not detected in EA individuals. Interferon signaling was observed in B cells in both ethnicities. Oxidative phosphorylation was found in age-related B cells (ABCs) for both ethnicities, whereas Death Receptor Signaling was found only in EA patients in these cells. Interferon-related transcription factors were elevated in ABCs and IFIT-Hi Naive B cells in SLE subjects of both ethnicities. Conclusions: ANA+ healthy individuals have altered gene expression pathways in B cells that might drive apoptosis and subsequent clinical autoimmune pathogenesis. Increases in certain regulatory pathways may delay progression to SLE. Further, AA individuals have more elevated activation pathways that may make them more susceptible to SLE.

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Authors: Jae Won Lee, Kyung Hyun Min, Hong Jae Lee, Sang Cheon Lee

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To date, imaging techniques have attracted much attention in medicine because the detection of diseases at an early stage provides greater opportunities for successful treatment. Consequently, over the past few decades, diverse imaging modalities including magnetic resonance (MR), positron emission tomography, computed tomography, and ultrasound (US) have been developed and applied widely in the field of clinical diagnosis. However, each of the above-mentioned imaging modalities possesses unique strengths and intrinsic weaknesses, which limit their abilities to provide accurate information. Therefore, multimodal imaging systems may be a solution that can provide improved diagnostic performance. Among the current medical imaging modalities, US is a widely available real-time imaging modality. It has many advantages including safety, low cost and easy access for patients. However, its low spatial resolution precludes accurate discrimination of diseased region such as cancer sites. In contrast, MR has no tissue-penetrating limit and can provide images possessing exquisite soft tissue contrast and high spatial resolution. However, it cannot offer real-time images and needs a comparatively long imaging time. The characteristics of these imaging modalities may be considered complementary, and the modalities have been frequently combined for the clinical diagnostic process. Biominerals such as calcium carbonate (CaCO3) and calcium phosphate (CaP) exhibit pH-dependent dissolution behavior. They demonstrate pH-controlled drug release due to the dissolution of minerals in acidic pH conditions. In particular, the application of this mineralization technique to a US contrast agent has been reported recently. The CaCO3 mineral reacts with acids and decomposes to generate calcium dioxide (CO2) gas in an acidic environment. These gas-generating mineralized nanoparticles generated CO2 bubbles in the acidic environment of the tumor, thereby allowing for strong echogenic US imaging of tumor tissues. On the basis of this previous work, it was hypothesized that the loading of MR contrast agents into the CaCO3 mineralized nanoparticles may be a novel strategy in designing a contrast agent for dual imaging. Herein, CaCO3 mineralized nanoparticles that were capable of generating CO2 bubbles to trigger the release of entrapped MR contrast agents in response to tumoral acidic pH were developed for the purposes of US and MR dual-modality imaging of tumors. Gd2O3 nanoparticles were selected as an MR contrast agent. A key strategy employed in this study was to prepare Gd2O3 nanoparticle-loaded mineralized nanoparticles (Gd2O3-MNPs) using block copolymer-templated CaCO3 mineralization in the presence of calcium cations (Ca2+), carbonate anions (CO32-) and positively charged Gd2O3 nanoparticles. The CaCO3 core was considered suitable because it may effectively shield Gd2O3 nanoparticles from water molecules in the blood (pH 7.4) before decomposing to generate CO2 gas, triggering the release of Gd2O3 nanoparticles in tumor tissues (pH 6.4~7.4). The kinetics of CaCO3 dissolution and CO2 generation from the Gd2O3-MNPs were examined as a function of pH and pH-dependent in vitro magnetic relaxation; additionally, the echogenic properties were estimated to demonstrate the potential of the particles for the tumor-specific US and MR imaging.

Keywords: calcium carbonate, mineralization, ultrasound imaging, magnetic resonance imaging

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Authors: Jenee Gooden, Kevin Vasquez-monterroso, Lady Paula Dejesus, Sandra Wainwright, Daniel Kim, Mackenzie Walker

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Introduction: Pyoderma gangrenosum (PG) is a rare, rapidly progressive, neutrophilic ulcerative colitis condition with an incidence of 3 to 10 cases per year ¹ ². Due to the similar appearance, PG is often misdiagnosed as a diabetic ulcer in diabetic patients. Though they may clinically appear similar in appearance, the treatment protocol and diagnostic criteria differ. Also, end-stage renal disease (ESRD) is often a condition seen in diabetic patients, which can have a significant impact on wound healing due to the wide range of uremic toxins³. This case study demonstrates a multidisciplinary team and multimodal treatment approach by podiatric surgery, general surgery, rheumatology, infectious disease, interventional cardiology, wound care and hyperbaric medicine for an uncontrolled diabetic with pyoderma gangrenosum of a significant circumferential wound, covering almost the entire right lower extremity. Methods:56 y.o male presents with multiple PG ulcerations, including the chest, right posterior lower extremity and sacrum. All ulcerations were previously managed by the same wound care specialist. His chief complaint was worsening PG ulcerations accompanied by a fever of 103 °F . This case study focuses on the wound to his RLE. Past medical history significant for diabetes mellitus type 2 with hemoglobin A1c of 10% and end stage renal disease (ESRD) on hemodialysis. A multidisciplinary team approach by podiatric surgery, general surgery, rheumatology, infectious disease, interventional cardiology, wound care and hyperbaric medicine was successfully used to perform right lower extremity limb salvage. The patient was managed by rheumatology for the continuation of prior medication, as well as the mutual agreement with wound care for the addition of dapsone. A coronary CT angiogram was performed by interventional cardiology, but no significant disease was noted, and no further vascular workup was necessary. Multiple surgical sharp wide excisional debridements with application of allografts and split thickness skin grafts for the circumferential ulceration that encompassed almost the entire right lower extremity were performed by both podiatric surgery and general surgery. Wound cultures and soft tissue biopsies were performed, and infectious disease managed antibiotic therapy. Hyperbaric oxygen therapy and wound vac therapy by wound care were also completed as adjunct management. Results: Prevention of leg amputation by limb salvage of the RLE was accomplished by a multidisciplinary team approach, with the wound size decreasing over a total of 29 weeks from 600 cm² to 12.0 x 3.5 x 0.2 cm. Our multidisciplinary team included podiatric surgery, general surgery, rheumatology, infectious disease, interventional cardiology, wound care and hyperbaric medicine. Discussion: Wound healing, in general, can have its challenges, and those challenges are only magnified when accompanied by multiple systemic illnesses. Though the negative impact of diabetes on wound healing is well known, the compound impact of being a diabetic with ESRD and having pyoderma gangrenosum is not. This case demonstrates the necessity for a multidisciplinary team approach with a wide array of treatment modalities to optimize wound healing and perform limb salvage with prevention of lower extremity amputation.

Keywords: diabetes, podiatry, pyoderma gangrenosum, end stage renal disease

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Authors: Vishal Kumar, Soumitra Satapathi

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Föster Resonance Energy Transfer (FRET) is a powerful technique used to probe close-range molecular interactions. Physically, the FRET phenomenon manifests as a dipole–dipole interaction between closely juxtaposed fluorescent molecules (10–100 Å). Our effort is to employ this FRET technique to make a prototype device for highly sensitive detection of environment pollutant. Among the most common environmental pollutants, nitroaromatic compounds (NACs) are of particular interest because of their durability and toxicity. That’s why, sensitive and selective detection of small amounts of nitroaromatic explosives, in particular, 2,4,6-trinitrophenol (TNP), 2,4-dinitrotoluene (DNT) and 2,4,6-trinitrotoluene (TNT) has been a critical challenge due to the increasing threat of explosive-based terrorism and the need of environmental monitoring of drinking and waste water. In addition, the excessive utilization of TNP in several other areas such as burn ointment, pesticides, glass and the leather industry resulted in environmental accumulation, and is eventually contaminating the soil and aquatic systems. To the date, high number of elegant methods, including fluorimetry, gas chromatography, mass, ion-mobility and Raman spectrometry have been successfully applied for explosive detection. Among these efforts, fluorescence-quenching methods based on the mechanism of FRET show good assembly flexibility, high selectivity and sensitivity. Here, we report a FRET-based sensor system for the highly selective detection of NACs, such as TNP, DNT and TNT. The sensor system is composed of a copolymer Poly [(N,N-dimethylacrylamide)-co-(Boc-Trp-EMA)] (RP) bearing tryptophan derivative in the side chain as donor and dansyl tagged copolymer P(MMA-co-Dansyl-Ala-HEMA) (DCP) as an acceptor. Initially, the inherent fluorescence of RP copolymer is quenched by non-radiative energy transfer to DCP which only happens once the two molecules are within Förster critical distance (R0). The excellent spectral overlap (Jλ= 6.08×10¹⁴ nm⁴M⁻¹cm⁻¹) between donors’ (RP) emission profile and acceptors’ (DCP) absorption profile makes them an exciting and efficient FRET pair i.e. further confirmed by the high rate of energy transfer from RP to DCP i.e. 0.87 ns⁻¹ and lifetime measurement by time correlated single photon counting (TCSPC) to validate the 64% FRET efficiency. This FRET pair exhibited a specific fluorescence response to NACs such as DNT, TNT and TNP with 5.4, 2.3 and 0.4 µM LODs, respectively. The detection of NACs occurs with high sensitivity by photoluminescence quenching of FRET signal induced by photo-induced electron transfer (PET) from electron-rich FRET pair to electron-deficient NAC molecules. The estimated stern-volmer constant (KSV) values for DNT, TNT and TNP are 6.9 × 10³, 7.0 × 10³ and 1.6 × 104 M⁻¹, respectively. The mechanistic details of molecular interactions are established by time-resolved fluorescence, steady-state fluorescence and absorption spectroscopy confirmed that the sensing process is of mixed type, i.e. both dynamic and static quenching as lifetime of FRET system (0.73 ns) is reduced to 0.55, 0.57 and 0.61 ns DNT, TNT and TNP, respectively. In summary, the simplicity and sensitivity of this novel FRET sensor opens up the possibility of designing optical sensor of various NACs in one single platform for developing multimodal sensor for environmental monitoring and future field based study.

Keywords: FRET, nitroaromatic, stern-Volmer constant, tryptophan and dansyl tagged copolymer

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Authors: Aliasghar Mehdizadeh Dastjerdi, Francisco Camara Pereira

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The increasing complexity and demand of transport services strains transportation systems especially in urban areas with limited possibilities for building new infrastructure. The solution to this challenge requires changes of travel behavior. One of the proposed means to induce such change is multimodal travel apps. This paper describes a study of the intention to use a real-time multi-modal travel app aimed at motivating travel behavior change in the Greater Copenhagen Region (Denmark) toward promoting sustainable transport options. The proposed app is a multi-faceted smartphone app including both travel information and persuasive strategies such as health and environmental feedback, tailoring travel options, self-monitoring, tunneling users toward green behavior, social networking, nudging and gamification elements. The prospective for mobility management travel apps to stimulate sustainable mobility rests not only on the original and proper employment of the behavior change strategies, but also on explicitly anchoring it on established theoretical constructs from behavioral theories. The theoretical foundation is important because it positively and significantly influences the effectiveness of the system. However, there is a gap in current knowledge regarding the study of mobility-management travel app with support in behavioral theories, which should be explored further. This study addresses this gap by a social cognitive theory‐based examination. However, compare to conventional method in technology adoption research, this study adopts a reverse approach in which the associations between theoretical constructs are explored by Max-Min Hill-Climbing (MMHC) algorithm as a hybrid causal discovery method. A technology-use preference survey was designed to collect data. The survey elicited different groups of variables including (1) three groups of user’s motives for using the app including gain motives (e.g., saving travel time and cost), hedonic motives (e.g., enjoyment) and normative motives (e.g., less travel-related CO2 production), (2) technology-related self-concepts (i.e. technophile attitude) and (3) use Intention of the travel app. The questionnaire items led to the formulation of causal relationships discovery to learn the causal structure of the data. Causal relationships discovery from observational data is a critical challenge and it has applications in different research fields. The estimated causal structure shows that the two constructs of gain motives and technophilia have a causal effect on adoption intention. Likewise, there is a causal relationship from technophilia to both gain and hedonic motives. In line with the findings of the prior studies, it highlights the importance of functional value of the travel app as well as technology self-concept as two important variables for adoption intention. Furthermore, the results indicate the effect of technophile attitude on developing gain and hedonic motives. The causal structure shows hierarchical associations between the three groups of user’s motive. They can be explained by “frustration-regression” principle according to Alderfer's ERG (Existence, Relatedness and Growth) theory of needs meaning that a higher level need remains unfulfilled, a person may regress to lower level needs that appear easier to satisfy. To conclude, this study shows the capability of causal discovery methods to learn the causal structure of theoretical model, and accordingly interpret established associations.

Keywords: travel app, behavior change, persuasive technology, travel information, causality

Procedia PDF Downloads 112

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

Procedia PDF Downloads 67

Authors: Jeremie Coullon, Robert J. Webber

Abstract:

We introduce a Markov chain Monte Carlo (MCMC) sam-pler for infinite-dimensional inverse problems. Our sam-pler is based on the affine invariant ensemble sampler, which uses interacting walkers to adapt to the covariance structure of the target distribution. We extend this ensem-ble sampler for the first time to infinite-dimensional func-tion spaces, yielding a highly efficient gradient-free MCMC algorithm. Because our ensemble sampler does not require gradients or posterior covariance estimates, it is simple to implement and broadly applicable. In many Bayes-ian inverse problems, Markov chain Monte Carlo (MCMC) meth-ods are needed to approximate distributions on infinite-dimensional function spaces, for example, in groundwater flow, medical imaging, and traffic flow. Yet designing efficient MCMC methods for function spaces has proved challenging. Recent gradi-ent-based MCMC methods preconditioned MCMC methods, and SMC methods have improved the computational efficiency of functional random walk. However, these samplers require gradi-ents or posterior covariance estimates that may be challenging to obtain. Calculating gradients is difficult or impossible in many high-dimensional inverse problems involving a numerical integra-tor with a black-box code base. Additionally, accurately estimating posterior covariances can require a lengthy pilot run or adaptation period. These concerns raise the question: is there a functional sampler that outperforms functional random walk without requir-ing gradients or posterior covariance estimates? To address this question, we consider a gradient-free sampler that avoids explicit covariance estimation yet adapts naturally to the covariance struc-ture of the sampled distribution. This sampler works by consider-ing an ensemble of walkers and interpolating and extrapolating between walkers to make a proposal. This is called the affine in-variant ensemble sampler (AIES), which is easy to tune, easy to parallelize, and efficient at sampling spaces of moderate dimen-sionality (less than 20). The main contribution of this work is to propose a functional ensemble sampler (FES) that combines func-tional random walk and AIES. To apply this sampler, we first cal-culate the Karhunen–Loeve (KL) expansion for the Bayesian prior distribution, assumed to be Gaussian and trace-class. Then, we use AIES to sample the posterior distribution on the low-wavenumber KL components and use the functional random walk to sample the posterior distribution on the high-wavenumber KL components. Alternating between AIES and functional random walk updates, we obtain our functional ensemble sampler that is efficient and easy to use without requiring detailed knowledge of the target dis-tribution. In past work, several authors have proposed splitting the Bayesian posterior into low-wavenumber and high-wavenumber components and then applying enhanced sampling to the low-wavenumber components. Yet compared to these other samplers, FES is unique in its simplicity and broad applicability. FES does not require any derivatives, and the need for derivative-free sam-plers has previously been emphasized. FES also eliminates the requirement for posterior covariance estimates. Lastly, FES is more efficient than other gradient-free samplers in our tests. In two nu-merical examples, we apply FES to challenging inverse problems that involve estimating a functional parameter and one or more scalar parameters. We compare the performance of functional random walk, FES, and an alternative derivative-free sampler that explicitly estimates the posterior covariance matrix. We conclude that FES is the fastest available gradient-free sampler for these challenging and multimodal test problems.

Keywords: Bayesian inverse problems, Markov chain Monte Carlo, infinite-dimensional inverse problems, dimensionality reduction

Procedia PDF Downloads 127

Authors: Fahimeh Palizban, Farshad Noravesh, Amir Hossein Saeidian, Mahya Mehrmohamadi

Abstract:

In the recent decade, the emergence of liquid biopsy has significantly improved cancer monitoring and detection. Dying cells, including those originating from tumors, shed their DNA into the blood and contribute to a pool of circulating fragments called cell-free DNA. Accordingly, identifying the tissue origin of these DNA fragments from the plasma can result in more accurate and fast disease diagnosis and precise treatment protocols. Open chromatin regions are important epigenetic features of DNA that reflect cell types of origin. Profiling these features by DNase-seq, ATAC-seq, and histone ChIP-seq provides insights into tissue-specific and disease-specific regulatory mechanisms. There have been several studies in the area of cancer liquid biopsy that integrate distinct genomic and epigenomic features for early cancer detection along with tissue of origin detection. However, multimodal analysis requires several types of experiments to cover the genomic and epigenomic aspects of a single sample, which will lead to a huge amount of cost and time. To overcome these limitations, the idea of predicting OCRs from WGS is of particular importance. In this regard, we proposed a computational approach to target the prediction of open chromatin regions as an important epigenetic feature from cell-free DNA whole genome sequence data. To fulfill this objective, local sequencing depth will be fed to our proposed algorithm and the prediction of the most probable open chromatin regions from whole genome sequencing data can be carried out. Our method integrates the signal processing method with sequencing depth data and includes count normalization, Discrete Fourie Transform conversion, graph construction, graph cut optimization by linear programming, and clustering. To validate the proposed method, we compared the output of the clustering (open chromatin region+, open chromatin region-) with previously validated open chromatin regions related to human blood samples of the ATAC-DB database. The percentage of overlap between predicted open chromatin regions and the experimentally validated regions obtained by ATAC-seq in ATAC-DB is greater than 67%, which indicates meaningful prediction. As it is evident, OCRs are mostly located in the transcription start sites (TSS) of the genes. In this regard, we compared the concordance between the predicted OCRs and the human genes TSS regions obtained from refTSS and it showed proper accordance around 52.04% and ~78% with all and the housekeeping genes, respectively. Accurately detecting open chromatin regions from plasma cell-free DNA-seq data is a very challenging computational problem due to the existence of several confounding factors, such as technical and biological variations. Although this approach is in its infancy, there has already been an attempt to apply it, which leads to a tool named OCRDetector with some restrictions like the need for highly depth cfDNA WGS data, prior information about OCRs distribution, and considering multiple features. However, we implemented a graph signal clustering based on a single depth feature in an unsupervised learning manner that resulted in faster performance and decent accuracy. Overall, we tried to investigate the epigenomic pattern of a cell-free DNA sample from a new computational perspective that can be used along with other tools to investigate genetic and epigenetic aspects of a single whole genome sequencing data for efficient liquid biopsy-related analysis.

Keywords: open chromatin regions, cancer, cell-free DNA, epigenomics, graph signal processing, correlation clustering

Procedia PDF Downloads 110

Authors: Subhash Nerella, Ziyuan Guan, Azra Bihorac, Parisa Rashidi

Abstract:

Intensive care units (ICUs) provide care to critically ill patients in severe and life-threatening conditions. However, patient monitoring in the ICU is limited by the time and resource constraints imposed on healthcare providers. Many critical care indices such as mobility are still manually assessed, which can be subjective, prone to human errors, and lack granularity. Other important aspects, such as environmental factors, are not monitored at all. For example, critically ill patients often experience circadian disruptions due to the absence of effective environmental “timekeepers” such as the light/dark cycle and the systemic effect of acute illness on chronobiologic markers. Although the occurrence of delirium is associated with circadian disruption risk factors, these factors are not routinely monitored in the ICU. Hence, there is a critical unmet need to develop systems for precise and real-time assessment through novel enabling technologies. We have developed the mobility and circadian disruption quantification system (Mobi-DiQ) by augmenting biomarker and clinical data with pervasive sensing data to generate mobility and circadian cues related to mobility, nightly disruptions, and light and noise exposure. We hypothesize that Mobi-DiQ can provide accurate mobility and circadian cues that correlate with bedside clinical mobility assessments and circadian biomarkers, ultimately important for delirium risk assessment and prevention. The collected multimodal dataset consists of depth images, Electromyography (EMG) data, patient extremity movement captured by accelerometers, ambient light levels, Sound Pressure Level (SPL), and indoor air quality measured by volatile organic compounds, and the equivalent CO₂ concentration. For delirium risk assessment, the system recognizes mobility cues (axial body movement features and body key points) and circadian cues, including nightly disruptions, ambient SPL, and light intensity, as well as other environmental factors such as indoor air quality. The Mobi-DiQ system consists of three major components: the pervasive sensing system, a data storage and analysis server, and a data annotation system. For data collection, six local pervasive sensing systems were deployed, including a local computer and sensors. A video recording tool with graphical user interface (GUI) developed in python was used to capture depth image frames for analyzing patient mobility. All sensor data is encrypted, then automatically uploaded to the Mobi-DiQ server through a secured VPN connection. Several data pipelines are developed to automate the data transfer, curation, and data preparation for annotation and model training. The data curation and post-processing are performed on the server. A custom secure annotation tool with GUI was developed to annotate depth activity data. The annotation tool is linked to the MongoDB database to record the data annotation and to provide summarization. Docker containers are also utilized to manage services and pipelines running on the server in an isolated manner. The processed clinical data and annotations are used to train and develop real-time pervasive sensing systems to augment clinical decision-making and promote targeted interventions. In the future, we intend to evaluate our system as a clinical implementation trial, as well as to refine and validate it by using other data sources, including neurological data obtained through continuous electroencephalography (EEG).

Keywords: deep learning, delirium, healthcare, pervasive sensing

Procedia PDF Downloads 65