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Commenced in January 2007
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Edition: International
Paper Count: 2266

Search results for: dental remains

106 The Measurement of City Brand Effectiveness as Methodological and Strategic Challenge: Insights from Individual Interviews with International Experts

Authors: A. Augustyn, M. Florek, M. Herezniak

Abstract:

Since the public authorities are constantly pressured by the public opinion to showcase the tangible and measurable results of their efforts, the evaluation of place brand-related activities becomes a necessity. Given the political and social character of place branding process, the legitimization of the branding efforts requires the compliance of the objectives set out in the city brand strategy with the actual needs, expectations, and aspirations of various internal stakeholders. To deliver on the diverse promises, city authorities and brand managers need to translate them into the measurable indicators against which the brand strategy effectiveness will be evaluated. In concert with these observations are the findings from branding and marketing literature with a widespread consensus that places should adopt a more systematic and holistic approach in order to ensure the performance of their brands. However, the measurement of the effectiveness of place branding remains insufficiently explored in theory, even though it is considered a significant step in the process of place brand management. Therefore, the aim of the research presented in the current paper was to collect insights on the nature of effectiveness measurement of city brand strategies and to juxtapose these findings with the theoretical assumptions formed on the basis of the state-of-the-art literature review. To this end, 15 international academic experts (out of 18 initially selected) with affiliation from ten countries (five continents), were individually interviewed. The standardized set of 19 open-ended questions was used for all the interviewees, who had been selected based on their expertise and reputation in the fields of place branding/marketing. Findings were categorized into four modules: (i) conceptualizations of city brand effectiveness, (ii) methodological issues of city brand effectiveness measurement, (iii) the nature of measurement process, (iv) articulation of key performance indicators (KPIs). Within each module, the interviewees offered diverse insights into the subject based on their academic expertise and professional activity as consultants. They proposed that there should be a twofold understanding of effectiveness. The narrow one when it is conceived as the aptitude to achieve specific goals, and the broad one in which city brand effectiveness is seen as an increase in social and economic reality of a place, which in turn poses diverse challenges for the measurement concepts and processes. Moreover, the respondents offered a variety of insights into the methodological issues, particularly about the need for customization and flexibility of the measurement systems, for the employment of interdisciplinary approach to measurement and implications resulting therefrom. Considerable emphasis was put on the inward approach to measurement, namely the necessity to monitor the resident’s evaluation of brand related activities instead of benchmarking cities against the competitive set. Other findings encompass the issues of developing appropriate KPIs for the city brand, managing the measurement process and the inclusion of diverse stakeholders to produce a sound measurement system. Furthermore, the interviewees enumerated the most frequently made mistakes in measurement mainly resulting from the misunderstanding of the nature of city brands. This research was financed by the National Science Centre, Poland, research project no. 2015/19/B/HS4/00380 Towards the categorization of place brand strategy effectiveness indicators – findings from strategic documents of Polish district cities – theoretical and empirical approach.

Keywords: city branding, effectiveness, experts’ insights, measurement

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105 More Than Financial Wealth: An Empirical Study on the Impact of Family Involvement on the Dimensions of Exit Success

Authors: Tim Vollmer, Andrea Greven, Malte Brettel

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Family firms represent the predominant business structure worldwide, accounting for 90 percent of all operational businesses. These firms are essential to society and the economy. In the past decade, family firm exits increased by 72%; and in the next five years, 95,000 German family firms will be sold, acquired, or liquidated. For family firms, socioemotional wealth represents the frame of reference and value to preserve when making decisions. Family firm exits threaten the socioemotional wealth, as in extreme scenarios, economic logic may take over. So, a dilemma arises: Maintaining socioemotional wealth versus pursuing financial wealth. Family firm researchers agree that family involvement leads to specific goals, behaviors, and outcomes. For instance, the desire to protect socioemotional wealth when selling the firm and the focus on particular exit success dimensions, depending on the family's role inside the firm. However, despite the regularity of family firm exits, there is little research on the effect of family involvement on the family firm CEOs' perceived exit performance. We investigate the family firm CEOs' perceived exit performance, which we call exit success. Considering the deficiencies in the literature, we identify two research gaps. First, it remains unclear how family involvement affects the dimensions of exit success. Hence, we provide evidence of which success dimensions matter most depending on the family's involvement and how to differentiate successful from unsuccessful exits. Second, prior work has analyzed family involvement in the socioemotional wealth context but found contradictory findings. This work considers, for example, the family generation in control and identifies the tipping point of economic objectives becoming preferable over socioemotional wealth-related goals. This paper theorizes and empirically investigates, through the lens of socioemotional wealth and conflict theory, how socioemotional wealth mediates the relationship between family involvement and family firms' exit success. We analyze family firms' exit success dimensions of personal financial benefits, personal reputation, employee benefits, and firm mission persistence. Family involvement considers the family firms' heterogeneity in ownership, management, and generation. We use a quantitative approach in the form of an online survey by drawing on 116 responses from former family firm CEOs'. This study highlights that socioemotional wealth mediates the relationship between the dimensions of family involvement and exit success. The greater socioemotional wealth, the greater the family firm CEOs focus on the pro-organizational exit success dimensions of employee benefits and firm mission persistence. In contrast, the self-regarding dimension of personal financial benefits is significantly negatively affected. An important finding is that later generations and the number of family managers involved significantly negatively affect the two pro-organizational dimensions of exit success. Family ownership does not show any significant effect. Our work widens implications for research, theory, and practice by contributing in two meaningful ways. First, our results offer insights to differentiate successful from unsuccessful family firm exits and provide evidence of which success dimensions matter and which to focus on, most dependent on the family's role inside the firm. Second, our article advances research and empirical understanding of family firms and socioemotional wealth by clarifying contradictory findings.

Keywords: exit success, family firm exit, perceived exit performance, socioemotional wealth

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104 “MaxSALIVA-II” Advancing a Nano-Sized Dual-Drug Delivery System for Salivary Gland Radioprotection, Regeneration and Repair in a Head and Neck Cancer Pre-Clinical Murine Model

Authors: Ziyad S. Haidar

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Background: Saliva plays a major role in maintaining oral, dental, and general health and well-being; where it normally bathes the oral cavity acting as a clearing agent. This becomes more apparent when the amount and quality of saliva are significantly reduced due to medications, salivary gland neoplasms, disorders such as Sjögren’s syndrome, and especially ionizing radiation therapy for tumors of the head and neck, the 5th most common malignancy worldwide, during which the salivary glands are included within the radiation field/zone. Clinically, patients affected by salivary gland dysfunction often opt to terminate their radiotherapy course prematurely as they become malnourished and experience a significant decrease in their QoL. Accordingly, the formulation of a radio-protection/-prevention modality and development of an alternative Rx to restore damaged salivary gland tissue is eagerly awaited and highly desirable. Objectives: Assess the pre-clinical radio-protective effect and reparative/regenerative potential of layer-by-layer self-assembled lipid-polymer-based core-shell nanocapsules designed and fine-tuned for the sequential (ordered) release of dual cytokines, following a single local administration (direct injection) into a murine sub-mandibular salivary gland model of irradiation. Methods: The formulated core-shell nanocapsules were characterized by physical-chemical-mechanically pre-/post-loading with the drugs, followed by optimizing the pharmaco-kinetic profile. Then, nanosuspensions were administered directly into the salivary glands, 24hrs pre-irradiation (PBS, un-loaded nanocapsules, and individual and combined vehicle-free cytokines were injected into the control glands for an in-depth comparative analysis). External irradiation at an elevated dose of 18Gy was exposed to the head-and-neck region of C57BL/6 mice. Salivary flow rate (un-stimulated) and salivary protein content/excretion were regularly assessed using an enzyme-linked immunosorbent assay (3-month period). Histological and histomorphometric evaluation and apoptosis/proliferation analysis followed by local versus systemic bio-distribution and immuno-histochemical assays were then performed on all harvested major organs (at the distinct experimental end-points). Results: Monodisperse, stable, and cytocompatible nanocapsules capable of maintaining the bioactivity of the encapsulant within the different compartments with the core and shell and with controlled/customizable pharmaco-kinetics, resulted, as is illustrated in the graphical abstract (Figure) below. The experimental animals demonstrated a significant increase in salivary flow rates when compared to the controls. Herein, salivary protein content was comparable to the pre-irradiation (baseline) level. Histomorphometry further confirmed the biocompatibility and localization of the nanocapsules, in vivo, into the site of injection. Acinar cells showed fewer vacuoles and nuclear aberration in the experimental group, while the amount of mucin was higher in controls. Overall, fewer apoptotic activities were detected by a Terminal deoxynucleotidyl Transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay and proliferative rates were similar to the controls, suggesting an interesting reparative and regenerative potential of irradiation-damaged/-dysfunctional salivary glands. The Figure below exemplifies some of these findings. Conclusions: Biocompatible, reproducible, and customizable self-assembling layer-by-layer core-shell delivery system is formulated and presented. Our findings suggest that localized sequential bioactive delivery of dual cytokines (in specific dose and order) can prevent irradiation-induced damage via reducing apoptosis and also has the potential to promote in situ proliferation of salivary gland cells; maxSALIVA is scalable (Good Manufacturing Practice or GMP production for human clinical trials) and patent-pending.

Keywords: cancer, head and neck, oncology, drug development, drug delivery systems, nanotechnology, nanoncology

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103 Scoping Review of the Potential to Embed Mental Health Impact in Global Challenges Research

Authors: Netalie Shloim, Brian Brown, Siobhan Hugh-Jones, Jane Plastow, Diana Setiyawati, Anna Madill

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In June 2021, the World Health Organization launched its guidance and technical packages on community mental health services, stressing a human rights-based approach to care. This initiative stems from an increasing acknowledgment of the role mental health plays in achieving the Sustainable Development Goals. Nevertheless, mental health remains a relatively neglected research area and the estimates for untreated mental disorders in low-and-middle-income countries (LMICs) are as high as 78% for adults. Moreover, the development sector and research programs too often side-line mental health as a privilege in the face of often immediate threats to life and livelihood. As a way of addressing this problem, this study aimed to examine past or ongoing GCRF projects to see if there were opportunities where mental health impact could have been achieved without compromising a study's main aim and without overburdening a project. Projects funded by the UKRI Global Challenges Research Fund (GCRF) were analyzed. This program was initiated in 2015 to support cutting-edge research that addresses the challenges faced by developing countries. By the end of May 2020, a total of 15,279 projects were funded of which only 3% had an explicit mental health focus. A sample of 36 non-mental-health-focused projects was then sampled for diversity across research council, challenge portfolio and world region. Each of these 36 projects was coded by two coders for opportunities to embed mental health impact. To facilitate coding, the literature was inspected for dimensions relevant to LMIC settings. Three main psychological and three main social dimensions were identified: promote a positive sense of self; promote positive emotions, safe expression and regulation of challenging emotions, coping strategies, and help-seeking; facilitate skills development; and facilitate community-building; preserve sociocultural identity; support community mobilization. Coding agreement was strong on missed opportunities for mental health impact on the three social dimensions: support community mobilization (92%), facilitate community building (83%), preserve socio-cultural identity (70%). Coding agreement was reasonably strong on missed opportunities for mental health impact on the three psychological dimensions: promote positive emotions (67%), facilitate skills development (61%), positive sense of self (58%). In order of frequency, the agreed perceived opportunities from the highest to lowest are: support community mobilization, facilitate community building, facilitate skills development, promote a positive sense of self, promote positive emotions, preserve sociocultural identity. All projects were considered to have an opportunity to support community mobilization and to facilitate skills development by at least one coder. Findings provided support that there were opportunities to embed mental health impact in research across the range of development sectors and identifies what kind of missed opportunities are most frequent. Hence, mainstreaming mental health has huge potential to tackle the lack of priority and funding it has attracted traditionally. The next steps are to understand the barriers to mainstreaming mental health and to work together to overcome them.

Keywords: GCRF, mental health, psychosocial wellbeing, LMIC

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102 Assessing Brain Targeting Efficiency of Ionisable Lipid Nanoparticles Encapsulating Cas9 mRNA/gGFP Following Different Routes of Administration in Mice

Authors: Meiling Yu, Nadia Rouatbi, Khuloud T. Al-Jamal

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Background: Treatment of neurological disorders with modern medical and surgical approaches remains difficult. Gene therapy, allowing the delivery of genetic materials that encodes potential therapeutic molecules, represents an attractive option. The treatment of brain diseases with gene therapy requires the gene-editing tool to be delivered efficiently to the central nervous system. In this study, we explored the efficiency of different delivery routes, namely intravenous (i.v.), intra-cranial (i.c.), and intra-nasal (i.n.), to deliver stable nucleic acid-lipid particles (SNALPs) containing gene-editing tools namely Cas9 mRNA and sgRNA encoding for GFP as a reporter protein. We hypothesise that SNALPs can reach the brain and perform gene-editing to different extents depending on the administration route. Intranasal administration (i.n.) offers an attractive and non-invasive way to access the brain circumventing the blood–brain barrier. Successful delivery of gene-editing tools to the brain offers a great opportunity for therapeutic target validation and nucleic acids therapeutics delivery to improve treatment options for a range of neurodegenerative diseases. In this study, we utilised Rosa26-Cas9 knock-in mice, expressing GFP, to study brain distribution and gene-editing efficiency of SNALPs after i.v.; i.c. and i.n. routes of administration. Methods: Single guide RNA (sgRNA) against GFP has been designed and validated by in vitro nuclease assay. SNALPs were formulated and characterised using dynamic light scattering. The encapsulation efficiency of nucleic acids (NA) was measured by RiboGreen™ assay. SNALPs were incubated in serum to assess their ability to protect NA from degradation. Rosa26-Cas9 knock-in mice were i.v., i.n., or i.c. administered with SNALPs to test in vivo gene-editing (GFP knockout) efficiency. SNALPs were given as three doses of 0.64 mg/kg sgGFP following i.v. and i.n. or a single dose of 0.25 mg/kg sgGFP following i.c.. knockout efficiency was assessed after seven days using Sanger Sequencing and Inference of CRISPR Edits (ICE) analysis. In vivo, the biodistribution of DiR labelled SNALPs (SNALPs-DiR) was assessed at 24h post-administration using IVIS Lumina Series III. Results: Serum-stable SNALPs produced were 130-140 nm in diameter with ~90% nucleic acid loading efficiency. SNALPs could reach and stay in the brain for up to 24h following i.v.; i.n. and i.c. administration. Decreasing GFP expression (around 50% after i.v. and i.c. and 20% following i.n.) was confirmed by optical imaging. Despite the small number of mice used, ICE analysis confirmed GFP knockout in mice brains. Additional studies are currently taking place to increase mice numbers. Conclusion: Results confirmed efficient gene knockout achieved by SNALPs in Rosa26-Cas9 knock-in mice expressing GFP following different routes of administrations in the following order i.v.= i.c.> i.n. Each of the administration routes has its pros and cons. The next stages of the project involve assessing gene-editing efficiency in wild-type mice and replacing GFP as a model target with therapeutic target genes implicated in Motor Neuron Disease pathology.

Keywords: CRISPR, nanoparticles, brain diseases, administration routes

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101 Treatment of Neuronal Defects by Bone Marrow Stem Cells Differentiation to Neuronal Cells Cultured on Gelatin-PLGA Scaffolds Coated with Nano-Particles

Authors: Alireza Shams, Ali Zamanian, Atefehe Shamosi, Farnaz Ghorbani

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Introduction: Although the application of a new strategy remains a remarkable challenge for treatment of disabilities due to neuronal defects, progress in Nanomedicine and tissue engineering, suggesting the new medical methods. One of the promising strategies for reconstruction and regeneration of nervous tissue is replacing of lost or damaged cells by specific scaffolds after Compressive, ischemic and traumatic injuries of central nervous system. Furthermore, ultrastructure, composition, and arrangement of tissue scaffolds are effective on cell grafts. We followed implantation and differentiation of mesenchyme stem cells to neural cells on Gelatin Polylactic-co-glycolic acid (PLGA) scaffolds coated with iron nanoparticles. The aim of this study was to evaluate the capability of stem cells to differentiate into motor neuron-like cells under topographical cues and morphogenic factors. Methods and Materials: Bone marrow mesenchymal stem cells (BMMSCs) was obtained by primary cell culturing of adult rat bone marrow got from femur bone by flushing method. BMMSCs were incubated with DMEM/F12 (Gibco), 15% FBS and 100 U/ml pen/strep as media. Then, BMMSCs seeded on Gel/PLGA scaffolds and tissue culture (TCP) polystyrene embedded and incorporated by Fe Nano particles (FeNPs) (Fe3o4 oxide (M w= 270.30 gr/mol.). For neuronal differentiation, 2×10 5 BMMSCs were seeded on Gel/PLGA/FeNPs scaffolds was cultured for 7 days and 0.5 µ mol. Retinoic acid, 100 µ mol. Ascorbic acid,10 ng/ml. Basic fibroblast growth factor (Sigma, USA), 250 μM Iso butyl methyl xanthine, 100 μM 2-mercaptoethanol, and 0.2 % B27 (Invitrogen, USA) added to media. Proliferation of BMMSCs was assessed by using MTT assay for cell survival. The morphology of BMMSCs and scaffolds was investigated by scanning electron microscopy analysis. Expression of neuron-specific markers was studied by immunohistochemistry method. Data were analyzed by analysis of variance, and statistical significance was determined by Turkey’s test. Results: Our results revealed that differentiation and survival of BMMSCs into motor neuron-like cells on Gel/PLGA/FeNPs as a biocompatible and biodegradable scaffolds were better than those cultured in Gel/PLGA in absence of FeNPs and TCP scaffolds. FeNPs had raised physical power but decreased capacity absorption of scaffolds. Well defined oriented pores in scaffolds due to FeNPs may activate differentiation and synchronized cells as a mechanoreceptor. Induction effects of magnetic FeNPs by One way flow of channels in scaffolds help to lead the cells and can facilitate direction of their growth processes. Discussion: Progression of biological properties of BMMSCs and the effects of FeNPs spreading under magnetic field was evaluated in this investigation. In vitro study showed that the Gel/PLGA/FeNPs scaffold provided a suitable structure for motor neuron-like cells differentiation. This could be a promising candidate for enhancing repair and regeneration in neural defects. Dynamic and static magnetic field for inducing and construction of cells can provide better results for further experimental studies.

Keywords: differentiation, mesenchymal stem cells, nano particles, neuronal defects, Scaffolds

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100 Evaluating the Accuracy of Biologically Relevant Variables Generated by ClimateAP

Authors: Jing Jiang, Wenhuan XU, Lei Zhang, Shiyi Zhang, Tongli Wang

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Climate data quality significantly affects the reliability of ecological modeling. In the Asia Pacific (AP) region, low-quality climate data hinders ecological modeling. ClimateAP, a software developed in 2017, generates high-quality climate data for the AP region, benefiting researchers in forestry and agriculture. However, its adoption remains limited. This study aims to confirm the validity of biologically relevant variable data generated by ClimateAP during the normal climate period through comparison with the currently available gridded data. Climate data from 2,366 weather stations were used to evaluate the prediction accuracy of ClimateAP in comparison with the commonly used gridded data from WorldClim1.4. Univariate regressions were applied to 48 monthly biologically relevant variables, and the relationship between the observational data and the predictions made by ClimateAP and WorldClim was evaluated using Adjusted R-Squared and Root Mean Squared Error (RMSE). Locations were categorized into mountainous and flat landforms, considering elevation, slope, ruggedness, and Topographic Position Index. Univariate regressions were then applied to all biologically relevant variables for each landform category. Random Forest (RF) models were implemented for the climatic niche modeling of Cunninghamia lanceolata. A comparative analysis of the prediction accuracies of RF models constructed with distinct climate data sources was conducted to evaluate their relative effectiveness. Biologically relevant variables were obtained from three unpublished Chinese meteorological datasets. ClimateAPv3.0 and WorldClim predictions were obtained from weather station coordinates and WorldClim1.4 rasters, respectively, for the normal climate period of 1961-1990. Occurrence data for Cunninghamia lanceolata came from integrated biodiversity databases with 3,745 unique points. ClimateAP explains a minimum of 94.74%, 97.77%, 96.89%, and 94.40% of monthly maximum, minimum, average temperature, and precipitation variances, respectively. It outperforms WorldClim in 37 biologically relevant variables with lower RMSE values. ClimateAP achieves higher R-squared values for the 12 monthly minimum temperature variables and consistently higher Adjusted R-squared values across all landforms for precipitation. ClimateAP's temperature data yields lower Adjusted R-squared values than gridded data in high-elevation, rugged, and mountainous areas but achieves higher values in mid-slope drainages, plains, open slopes, and upper slopes. Using ClimateAP improves the prediction accuracy of tree occurrence from 77.90% to 82.77%. The biologically relevant climate data produced by ClimateAP is validated based on evaluations using observations from weather stations. The use of ClimateAP leads to an improvement in data quality, especially in non-mountainous regions. The results also suggest that using biologically relevant variables generated by ClimateAP can slightly enhance climatic niche modeling for tree species, offering a better understanding of tree species adaptation and resilience compared to using gridded data.

Keywords: climate data validation, data quality, Asia pacific climate, climatic niche modeling, random forest models, tree species

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99 A Rapid Assessment of the Impacts of COVID-19 on Overseas Labor Migration: Findings from Bangladesh

Authors: Vaiddehi Bansal, Ridhi Sahai, Kareem Kysia

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Overseas labor migration is currently one of the most important contributors to the economy of Bangladesh and is a highly profitable form of labor for Gulf Cooperative Council (GCC) countries. In 2019, 700,159 migrant workers from Bangladeshtraveled abroad for employment. GCC countries are a major destination for Bangladeshi migrant workers, with Saudi Arabia being the most common destination for Bangladeshi migrant workers since 2016. Despite the high rate of migration between these countries every year, the OLR industry remains complex and often leaves migrants susceptible to human trafficking, forced labor, and modern slavery. While the prevalence of forced labor among Bangladeshi migrants in GCC countries is still unknown, the IOM estimates international migrant workers comprise one fourth of the victims of forced labor. Moreover, the onset of the global COVID-19 pandemic has exposed migrant workers to additional adverse situations, making them even more vulnerable to forced labor and health risks. This paper presents findings from a rapid assessment of the impacts of COVID-19 on OLR in Bangladesh, with an emphasis on the increased risk of forced labor among vulnerable migrant worker populations, particularly women.Rapid reviews are a useful approach to swiftly provide actionable evidence for informed decision-making during emergencies, such as the COVID-19 pandemic. The research team conducted semi-structured key information interviews (KIIs) with a range of stakeholders, including government officials, local NGOs, international organizations, migration researchers, and formal and informal recruiting agencies, to obtain insights on the multi-facted impacts of COVID-19 on the OLR sector. The research team also conducted a comprehensive review of available resources, including media articles, blogs, policy briefs, reports, white papers, and other online content, to triangulate findings from the KIIs. After screening for inclusion criteria, a total of 110 grey literature documents were included in the review. A total of 31 KIIs were conducted, data from which was transcribed and translated from Bangla to English, andanalyzed using a detailed codebook. Findings indicate that there was limited reintegration support for returnee migrants. Facing increasing amounts of debt, financial insecurity, and social discrimination, returnee migrants, were extremely vulnerable to forced labor and exploitation. Growing financial debt and limited job opportunities in their home country will likely push migrants to resort to unsafe migration channels. Evidence suggests that women, who are primarily domestic works in GCC countries, were exposed to increased risk of forced labor and workplace violence. Due to stay-at-home measures, women migrant workers were tasked with additional housekeeping working and subjected to longer work hours, wage withholding, and physical abuse. In Bangladesh, returnee women migrant workers also faced an increased risk of domestic violence.

Keywords: forced labor, migration, gender, human trafficking

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98 Modelling of Reactive Methodologies in Auto-Scaling Time-Sensitive Services With a MAPE-K Architecture

Authors: Óscar Muñoz Garrigós, José Manuel Bernabeu Aubán

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Time-sensitive services are the base of the cloud services industry. Keeping low service saturation is essential for controlling response time. All auto-scalable services make use of reactive auto-scaling. However, reactive auto-scaling has few in-depth studies. This presentation shows a model for reactive auto-scaling methodologies with a MAPE-k architecture. Queuing theory can compute different properties of static services but lacks some parameters related to the transition between models. Our model uses queuing theory parameters to relate the transition between models. It associates MAPE-k related times, the sampling frequency, the cooldown period, the number of requests that an instance can handle per unit of time, the number of incoming requests at a time instant, and a function that describes the acceleration in the service's ability to handle more requests. This model is later used as a solution to horizontally auto-scale time-sensitive services composed of microservices, reevaluating the model’s parameters periodically to allocate resources. The solution requires limiting the acceleration of the growth in the number of incoming requests to keep a constrained response time. Business benefits determine such limits. The solution can add a dynamic number of instances and remains valid under different system sizes. The study includes performance recommendations to improve results according to the incoming load shape and business benefits. The exposed methodology is tested in a simulation. The simulator contains a load generator and a service composed of two microservices, where the frontend microservice depends on a backend microservice with a 1:1 request relation ratio. A common request takes 2.3 seconds to be computed by the service and is discarded if it takes more than 7 seconds. Both microservices contain a load balancer that assigns requests to the less loaded instance and preemptively discards requests if they are not finished in time to prevent resource saturation. When load decreases, instances with lower load are kept in the backlog where no more requests are assigned. If the load grows and an instance in the backlog is required, it returns to the running state, but if it finishes the computation of all requests and is no longer required, it is permanently deallocated. A few load patterns are required to represent the worst-case scenario for reactive systems: the following scenarios test response times, resource consumption and business costs. The first scenario is a burst-load scenario. All methodologies will discard requests if the rapidness of the burst is high enough. This scenario focuses on the number of discarded requests and the variance of the response time. The second scenario contains sudden load drops followed by bursts to observe how the methodology behaves when releasing resources that are lately required. The third scenario contains diverse growth accelerations in the number of incoming requests to observe how approaches that add a different number of instances can handle the load with less business cost. The exposed methodology is compared against a multiple threshold CPU methodology allocating/deallocating 10 or 20 instances, outperforming the competitor in all studied metrics.

Keywords: reactive auto-scaling, auto-scaling, microservices, cloud computing

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97 Design, Fabrication and Analysis of Molded and Direct 3D-Printed Soft Pneumatic Actuators

Authors: N. Naz, A. D. Domenico, M. N. Huda

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Soft Robotics is a rapidly growing multidisciplinary field where robots are fabricated using highly deformable materials motivated by bioinspired designs. The high dexterity and adaptability to the external environments during contact make soft robots ideal for applications such as gripping delicate objects, locomotion, and biomedical devices. The actuation system of soft robots mainly includes fluidic, tendon-driven, and smart material actuation. Among them, Soft Pneumatic Actuator, also known as SPA, remains the most popular choice due to its flexibility, safety, easy implementation, and cost-effectiveness. However, at present, most of the fabrication of SPA is still based on traditional molding and casting techniques where the mold is 3d printed into which silicone rubber is cast and consolidated. This conventional method is time-consuming and involves intensive manual labour with the limitation of repeatability and accuracy in design. Recent advancements in direct 3d printing of different soft materials can significantly reduce the repetitive manual task with an ability to fabricate complex geometries and multicomponent designs in a single manufacturing step. The aim of this research work is to design and analyse the Soft Pneumatic Actuator (SPA) utilizing both conventional casting and modern direct 3d printing technologies. The mold of the SPA for traditional casting is 3d printed using fused deposition modeling (FDM) with the polylactic acid (PLA) thermoplastic wire. Hyperelastic soft materials such as Ecoflex-0030/0050 are cast into the mold and consolidated using a lab oven. The bending behaviour is observed experimentally with different pressures of air compressor to ensure uniform bending without any failure. For direct 3D-printing of SPA fused deposition modeling (FDM) with thermoplastic polyurethane (TPU) and stereolithography (SLA) with an elastic resin are used. The actuator is modeled using the finite element method (FEM) to analyse the nonlinear bending behaviour, stress concentration and strain distribution of different hyperelastic materials after pressurization. FEM analysis is carried out using Ansys Workbench software with a Yeon-2nd order hyperelastic material model. FEM includes long-shape deformation, contact between surfaces, and gravity influences. For mesh generation, quadratic tetrahedron, hybrid, and constant pressure mesh are used. SPA is connected to a baseplate that is in connection with the air compressor. A fixed boundary is applied on the baseplate, and static pressure is applied orthogonally to all surfaces of the internal chambers and channels with a closed continuum model. The simulated results from FEM are compared with the experimental results. The experiments are performed in a laboratory set-up where the developed SPA is connected to a compressed air source with a pressure gauge. A comparison study based on performance analysis is done between FDM and SLA printed SPA with the molded counterparts. Furthermore, the molded and 3d printed SPA has been used to develop a three-finger soft pneumatic gripper and has been tested for handling delicate objects.

Keywords: finite element method, fused deposition modeling, hyperelastic, soft pneumatic actuator

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96 Autophagy Promotes Vascular Smooth Muscle Cell Migration in vitro and in vivo

Authors: Changhan Ouyang, Zhonglin Xie

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In response to proatherosclerotic factors such as oxidized lipids, or to therapeutic interventions such as angioplasty, stents, or bypass surgery, vascular smooth muscle cells (VSMCs) migrate from the media to the intima, resulting in intimal hyperplasia, restenosis, graft failure, or atherosclerosis. These proatherosclerotic factors also activate autophagy in VSMCs. However, the functional role of autophagy in vascular health and disease remains poorly understood. In the present study, we determined the role of autophagy in the regulation of VSMC migration. Autophagy activity in cultured human aortic smooth muscle cells (HASMCs) and mouse carotid arteries was measured by Western blot analysis of microtubule-associated protein 1 light chain 3 B (LC3B) and P62. The VSMC migration was determined by scratch wound assay and transwell migration assay. Ex vivo smooth muscle cell migration was determined using aortic ring assay. The in vivo SMC migration was examined by staining the carotid artery sections with smooth muscle alpha actin (alpha SMA) after carotid artery ligation. To examine the relationship between autophagy and neointimal hyperplasia, C57BL/6J mice were subjected to carotid artery ligation. Seven days after injury, protein levels of Atg5, Atg7, Beclin1, and LC3B drastically increased and remained higher in the injured arteries three weeks after the injury. In parallel with the activation of autophagy, vascular injury-induced neointimal hyperplasia as estimated by increased intima/media ratio. The en face staining of carotid artery showed that vascular injury enhanced alpha SMA staining in the intimal cells as compared with the sham operation. Treatment of HASMCs with platelet-derived growth factor (PDGF), one of the major factors for vascular remodeling in response to vascular injury, increased Atg7 and LC3 II protein levels and enhanced autophagosome formation. In addition, aortic ring assay demonstrated that PDGF treated aortic rings displayed an increase in neovessel formation compared with control rings. Whole mount staining for CD31 and alpha SMA in PDGF treated neovessels revealed that the neovessel structures were stained by alpha SMA but not CD31. In contrast, pharmacological and genetic suppression of autophagy inhibits VSMC migration. Especially, gene silencing of Atg7 inhibited VSMC migration induced by PDGF. Furthermore, three weeks after ligation, markedly decreased neointimal formation was found in mice treated with chloroquine, an inhibitor of autophagy. Quantitative morphometric analysis of the injured vessels revealed a marked reduction in the intima/media ratio in the mice treated with chloroquine. Conclusion: Autophagy activation increases VSMC migration while autophagy suppression inhibits VSMC migration. These findings suggest that autophagy suppression may be an important therapeutic strategy for atherosclerosis and intimal hyperplasia.

Keywords: autophagy, vascular smooth muscle cell, migration, neointimal formation

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95 Decreased Tricarboxylic Acid (TCA) Cycle Staphylococcus aureus Increases Survival to Innate Immunity

Authors: Trenten Theis, Trevor Daubert, Kennedy Kluthe, Austin Nuxoll

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Staphylococcus aureus is a gram-positive bacterium responsible for an estimated 23,000 deaths in the United States and 25,000 deaths in the European Union annually. Recurring S. aureus bacteremia is associated with biofilm-mediated infections and can occur in 5 - 20% of cases, even with the use of antibiotics. Despite these infections being caused by drug-susceptible pathogens, they are surprisingly difficult to eradicate. One potential explanation for this is the presence of persister cells—a dormant type of cell that shows a high tolerance to antibiotic treatment. Recent studies have shown a connection between low intracellular ATP and persister cell formation. Specifically, this decrease in ATP, and therefore increase in persister cell formation, is due to an interrupted tricarboxylic acid (TCA) cycle. However, S. aureus persister cells’ role in pathogenesis remains unclear. Initial studies have shown that a fumC (TCA cycle gene) knockout survives challenge from aspects of the innate immune system better than wild-type S. aureus. Specifically, challenges from two antimicrobial peptides--LL-37 and hBD-3—show a log increase in survival of the fumC::N∑ strain compared to wild type S. aureus after 18 hours. Furthermore, preliminary studies show that the fumC knockout has a log more survival within a macrophage. These data lead us to hypothesize that the fumC knockout is better suited to other aspects of the innate immune system compared to wild-type S. aureus. To further investigate the mechanism for increased survival of fumC::N∑ within a macrophage, we tested bacterial growth in the presence of reactive oxygen species (ROS), reactive nitrogen species (RNS), and a low pH. Preliminary results suggest that the fumC knockout has increased growth compared to wild-type S. aureus in the presence of all three antimicrobial factors; however, no difference was observed in any single factor alone. To investigate survival within a host, a nine-day biofilm-associated catheter infection was performed on 6–8-week-old male and female C57Bl/6 mice. Although both sexes struggled to clear the infection, female mice were trending toward more frequently clearing the HG003 wild-type infection compared to the fumC::N∑ infection. One possible reason for the inability to reduce the bacterial burden is that biofilms are largely composed of persister cells. To test this hypothesis further, flow cytometry in conjunction with a persister cell marker was used to measure persister cells within a biofilm. Cap5A (a known persister cell marker) expression was found to be increased in a maturing biofilm, with the lowest levels of expression seen in immature biofilms and the highest expression exhibited by the 48-hour biofilm. Additionally, bacterial cells in a biofilm state closely resemble persister cells and exhibit reduced membrane potential compared to cells in planktonic culture, further suggesting biofilms are largely made up of persister cells. These data may provide an explanation as to why infections caused by antibiotic-susceptible strains remain difficult to treat.

Keywords: antibiotic tolerance, Staphylococcus aureus, host-pathogen interactions, microbial pathogenesis

Procedia PDF Downloads 157
94 Generating Biogas from Municipal Kitchen Waste: An Experience from Gaibandha, Bangladesh

Authors: Taif Rocky, Uttam Saha, Mahobul Islam

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With a rapid urbanisation in Bangladesh, waste management remains one of the core challenges. Turning municipal waste into biogas for mass usage is a solution that Bangladesh needs to adopt urgently. Practical Action with its commitment to challenging poverty with technological justice has piloted such idea in Gaibandha. The initiative received immense success and drew the attention of policy makers and practitioners. We believe, biogas from waste can highly contribute to meet the growing demand for energy in the country at present and in the future. Practical Action has field based experience in promoting small scale and innovative technologies. We have proven track record in integrated solid waste management. We further utilized this experience to promote waste to biogas at end users’ level. In 2011, we have piloted a project on waste to biogas in Gaibandha, a northern secondary town of Bangladesh. With resource and support from UNICEF and with our own innovative funds we have established a complete chain of utilizing waste to the renewable energy source and organic fertilizer. Biogas is produced from municipal solid waste, which is properly collected, transported and segregated by private entrepreneurs. The project has two major focuses, diversification of biogas end use and establishing a public-private partnership business model. The project benefits include Recycling of Wastes, Improved institutional (municipal) capacity, Livelihood from improved services and Direct Income from the project. Project risks include Change of municipal leadership, Traditional mindset, Access to decision making, Land availability. We have observed several outcomes from the initiative. Up scaling such an initiative will certainly contribute for sustainable cleaner and healthier urban environment and urban poverty reduction. - It reduces the unsafe disposal of wastes which improve the cleanliness and environment of the town. -Make drainage system effective reducing the adverse impact of water logging or flooding. -Improve public health from better management of wastes. -Promotes usage of biogas replacing the use of firewood/coal which creates smoke and indoor air pollution in kitchens which have long term impact on health of women and children. -Reduce the greenhouse gas emission from the anaerobic recycling of wastes and contributes to sustainable urban environment. -Promote the concept of agroecology from the uses of bio slurry/compost which contributes to food security. -Creates green jobs from waste value chain which impacts on poverty alleviation of urban extreme poor. -Improve municipal governance from inclusive waste services and functional partnership with private sectors. -Contribute to the implementation of 3R (Reduce, Reuse, Recycle) Strategy and Employment Creation of extreme poor to achieve the target set in Vision 2021 by Government of Bangladesh.

Keywords: kitchen waste, secondary town, biogas, segregation

Procedia PDF Downloads 190
93 Government and Non-Government Policy Responses to Anti-Trafficking Initiatives: A Discursive Analysis of the Construction of the Problem of Human Trafficking in Australia and Thailand

Authors: Jessica J. Gillies

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Human trafficking is a gross violation of human rights and thus invokes a strong response particularly throughout the global academic community. A longstanding tension throughout academic debate remains the question of a relationship between anti-trafficking policy and sex industry policy. In Australia, over the previous decade, many human trafficking investigations have related to the sexual exploitation of female victims, and convictions in Australia to date have often been for trafficking women from Thailand. Sex industry policy in Australia varies between states, providing a rich contextual landscape in which to explore this relationship. The purpose of this study was to deconstruct how meaning is constructed surrounding human trafficking throughout these supposedly related political discourses in Australia. In order to analyse the discursive construction of the problem of human trafficking in relation to sex industry policy, a discursive analysis was conducted. The methodology of the study was informed by a feminist theoretical framework, and included academic sources and grey literature such as organisational reports and policy statements regarding anti-trafficking initiatives. The scope of grey literature was restricted to Australian and Thai government and non-government organisation texts. The chosen methodology facilitated a qualitative exploration of the influence of feminist discourses over political discourse in this arena. The discursive analysis exposed clusters of active feminist debates interacting with sex industry policy within individual states throughout Australia. Additionally, strongly opposed sex industry perspectives were uncovered within these competing feminist frameworks. While the influence these groups may exert over policy differs, the debate constructs a discursive relationship between human trafficking and sex industry policy. This is problematic because anti-trafficking policy is drawn to some extent from this discursive construction, therefore affecting support services for survivors of human trafficking. The discursive analysis further revealed misalignment between government and non-government priorities, Australian government anti-trafficking policy appears to favour criminal justice priorities; whereas non-government settings preference human rights protections. Criminal justice priorities invoke questions of legitimacy, leading to strict eligibility policy for survivors seeking support following exploitation in the Australian sex industry, undermining women’s agency and human rights. In practice, these two main findings demonstrate a construction of policy that has serious outcomes on typical survivors in Australia following a lived experience of human trafficking for the purpose of sexual exploitation. The discourses constructed by conflicting feminist arguments influence political discourses throughout Australia. The application of a feminist theoretical framework to the discursive analysis of the problem of human trafficking is unique to this study. The study has exposed a longstanding and unresolved feminist debate that has filtered throughout anti-trafficking political discourse. This study illuminates the problematic construction of anti-trafficking policy, and the implications in practice on survivor support services. Australia has received international criticism for the focus on criminal justice rather than human rights throughout anti-trafficking policy discourse. The outcome of this study has the potential to inform future language and constructive conversations contributing to knowledge around how policy effects survivors in the post trafficking experience.

Keywords: Australia, discursive analysis, government, human trafficking, non-government, Thailand

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92 A Randomized, Controlled Trial to Test Behavior Change Techniques to Improve Low Intensity Physical Activity in Older Adults

Authors: Ciaran Friel, Jerry Suls, Mark Butler, Patrick Robles, Samantha Gordon, Frank Vicari, Karina W. Davidson

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Physical activity guidelines focus on increasing moderate-intensity activity for older adults, but adherence to recommendations remains low. This is despite the fact that scientific evidence supports that any increase in physical activity is positively correlated with health benefits. Behavior change techniques (BCTs) have demonstrated effectiveness in reducing sedentary behavior and promoting physical activity. This pilot study uses a Personalized Trials (N-of-1) design to evaluate the efficacy of using four BCTs to promote an increase in low-intensity physical activity (2,000 steps of walking per day) in adults aged 45-75 years old. The 4 BCTs tested were goal setting, action planning, feedback, and self-monitoring. BCTs were tested in random order and delivered by text message prompts requiring participant engagement. The study recruited health system employees in the target age range, without mobility restrictions and demonstrating interest in increasing their daily activity by a minimum of 2,000 steps per day for a minimum of five days per week. Participants were sent a Fitbit® fitness tracker with an established study account and password. Participants were recommended to wear the Fitbit device 24/7 but were required to wear it for a minimum of ten hours per day. Baseline physical activity was measured by Fitbit for two weeks. In the 8-week intervention phase of the study, participants received each of the four BCTs, in random order, for a two-week period. Text message prompts were delivered daily each morning at a consistent time. All prompts required participant engagement to acknowledge receipt of the BCT message. Engagement is dependent upon the BCT message and may have included recording that a detailed plan for walking has been made or confirmed a daily step goal (action planning, goal setting). Additionally, participants may have been directed to a study dashboard to view their step counts or compare themselves to their baseline average step count (self-monitoring, feedback). At the end of each two-week testing interval, participants were asked to complete the Self-Efficacy for Walking Scale (SEW_Dur), a validated measure that assesses the participant’s confidence in walking incremental distances, and a survey measuring their satisfaction with the individual BCT that they tested. At the end of their trial, participants received a personalized summary of their step data in response to each individual BCT. The analysis will examine the novel individual-level heterogeneity of treatment effect made possible by N-of-1 design and pool results across participants to efficiently estimate the overall efficacy of the selected behavioral change techniques in increasing low-intensity walking by 2,000 steps, five days per week. Self-efficacy will be explored as the likely mechanism of action prompting behavior change. This study will inform the providers and demonstrate the feasibility of an N-of-1 study design to effectively promote physical activity as a component of healthy aging.

Keywords: aging, exercise, habit, walking

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91 Identification of Failures Occurring on a System on Chip Exposed to a Neutron Beam for Safety Applications

Authors: S. Thomet, S. De-Paoli, F. Ghaffari, J. M. Daveau, P. Roche, O. Romain

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In this paper, we present a hardware module dedicated to understanding the fail reason of a System on Chip (SoC) exposed to a particle beam. Impact of Single-Event Effects (SEE) on processor-based SoCs is a concern that has increased in the past decade, particularly for terrestrial applications with automotive safety increasing requirements, as well as consumer and industrial domains. The SEE created by the impact of a particle on an SoC may have consequences that can end to instability or crashes. Specific hardening techniques for hardware and software have been developed to make such systems more reliable. SoC is then qualified using cosmic ray Accelerated Soft-Error Rate (ASER) to ensure the Soft-Error Rate (SER) remains in mission profiles. Understanding where errors are occurring is another challenge because of the complexity of operations performed in an SoC. Common techniques to monitor an SoC running under a beam are based on non-intrusive debug, consisting of recording the program counter and doing some consistency checking on the fly. To detect and understand SEE, we have developed a module embedded within the SoC that provide support for recording probes, hardware watchpoints, and a memory mapped register bank dedicated to software usage. To identify CPU failure modes and the most important resources to probe, we have carried out a fault injection campaign on the RTL model of the SoC. Probes are placed on generic CPU registers and bus accesses. They highlight the propagation of errors and allow identifying the failure modes. Typical resulting errors are bit-flips in resources creating bad addresses, illegal instructions, longer than expected loops, or incorrect bus accesses. Although our module is processor agnostic, it has been interfaced to a RISC-V by probing some of the processor registers. Probes are then recorded in a ring buffer. Associated hardware watchpoints are allowing to do some control, such as start or stop event recording or halt the processor. Finally, the module is also providing a bank of registers where the firmware running on the SoC can log information. Typical usage is for operating system context switch recording. The module is connected to a dedicated debug bus and is interfaced to a remote controller via a debugger link. Thus, a remote controller can interact with the monitoring module without any intrusiveness on the SoC. Moreover, in case of CPU unresponsiveness, or system-bus stall, the recorded information can still be recovered, providing the fail reason. A preliminary version of the module has been integrated into a test chip currently being manufactured at ST in 28-nm FDSOI technology. The module has been triplicated to provide reliable information on the SoC behavior. As the primary application domain is automotive and safety, the efficiency of the module will be evaluated by exposing the test chip under a fast-neutron beam by the end of the year. In the meantime, it will be tested with alpha particles and electromagnetic fault injection (EMFI). We will report in the paper on fault-injection results as well as irradiation results.

Keywords: fault injection, SoC fail reason, SoC soft error rate, terrestrial application

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90 Characterizing the Rectification Process for Designing Scoliosis Braces: Towards Digital Brace Design

Authors: Inigo Sanz-Pena, Shanika Arachchi, Dilani Dhammika, Sanjaya Mallikarachchi, Jeewantha S. Bandula, Alison H. McGregor, Nicolas Newell

Abstract:

The use of orthotic braces for adolescent idiopathic scoliosis (AIS) patients is the most common non-surgical treatment to prevent deformity progression. The traditional method to create an orthotic brace involves casting the patient’s torso to obtain a representative geometry, which is then rectified by an orthotist to the desired geometry of the brace. Recent improvements in 3D scanning technologies, rectification software, CNC, and additive manufacturing processes have given the possibility to compliment, or in some cases, replace manual methods with digital approaches. However, the rectification process remains dependent on the orthotist’s skills. Therefore, the rectification process needs to be carefully characterized to ensure that braces designed through a digital workflow are as efficient as those created using a manual process. The aim of this study is to compare 3D scans of patients with AIS against 3D scans of both pre- and post-rectified casts that have been manually shaped by an orthotist. Six AIS patients were recruited from the Ragama Rehabilitation Clinic, Colombo, Sri Lanka. All patients were between 10 and 15 years old, were skeletally immature (Risser grade 0-3), and had Cobb angles between 20-45°. Seven spherical markers were placed at key anatomical locations on each patient’s torso and on the pre- and post-rectified molds so that distances could be reliably measured. 3D scans were obtained of 1) the patient’s torso and pelvis, 2) the patient’s pre-rectification plaster mold, and 3) the patient’s post-rectification plaster mold using a Structure Sensor Mark II 3D scanner (Occipital Inc., USA). 3D stick body models were created for each scan to represent the distances between anatomical landmarks. The 3D stick models were used to analyze the changes in position and orientation of the anatomical landmarks between scans using Blender open-source software. 3D Surface deviation maps represented volume differences between the scans using CloudCompare open-source software. The 3D stick body models showed changes in the position and orientation of thorax anatomical landmarks between the patient and the post-rectification scans for all patients. Anatomical landmark position and volume differences were seen between 3D scans of the patient’s torsos and the pre-rectified molds. Between the pre- and post-rectified molds, material removal was consistently seen on the anterior side of the thorax and the lateral areas below the ribcage. Volume differences were seen in areas where the orthotist planned to place pressure pads (usually at the trochanter on the side to which the lumbar curve was tilted (trochanter pad), at the lumbar apical vertebra (lumbar pad), on the rib connected to the apical vertebrae at the mid-axillary line (thoracic pad), and on the ribs corresponding to the upper thoracic vertebra (axillary extension pad)). The rectification process requires the skill and experience of an orthotist; however, this study demonstrates that the brace shape, location, and volume of material removed from the pre-rectification mold can be characterized and quantified. Results from this study can be fed into software that can accelerate the brace design process and make steps towards the automated digital rectification process.

Keywords: additive manufacturing, orthotics, scoliosis brace design, sculpting software, spinal deformity

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89 Possible Involvement of DNA-methyltransferase and Histone Deacetylase in the Regulation of Virulence Potential of Acanthamoeba castellanii

Authors: Yi H. Wong, Li L. Chan, Chee O. Leong, Stephen Ambu, Joon W. Mak, Priyadashi S. Sahu

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Background: Acanthamoeba is a free-living opportunistic protist which is ubiquitously distributed in the environment. Virulent Acanthamoeba can cause fatal encephalitis in immunocompromised patients and potential blinding keratitis in immunocompetent contact lens wearers. Approximately 24 species have been identified but only the A. castellanii, A. polyphaga and A. culbertsoni are commonly associated with human infections. Until to date, the precise molecular basis for Acanthamoeba pathogenesis remains unclear. Previous studies reported that Acanthamoeba virulence can be diminished through prolonged axenic culture but revived through serial mouse passages. As no clear explanation on this reversible pathogenesis is established, hereby, we postulate that the epigenetic regulators, DNA-methyltransferases (DNMT) and histone-deacetylases (HDAC), could possibly be involved in granting the virulence plasticity of Acanthamoeba spp. Methods: Four rounds of mouse passages were conducted to revive the virulence potential of the virulence-attenuated Acanthamoeba castellanii strain (ATCC 50492). Briefly, each mouse (n=6/group) was inoculated intraperitoneally with Acanthamoebae cells (2x 105 trophozoites/mouse) and incubated for 2 months. Acanthamoebae cells were isolated from infected mouse organs by culture method and subjected to subsequent mouse passage. In vitro cytopathic, encystment and gelatinolytic assays were conducted to evaluate the virulence characteristics of Acanthamoebae isolates for each passage. PCR primers which targeted on the 2 members (DNMT1 and DNMT2) and 5 members (HDAC1 to 5) of the DNMT and HDAC gene families respectively were custom designed. Quantitative real-time PCR (qPCR) was performed to detect and quantify the relative expression of the two gene families in each Acanthamoeba isolates. Beta-tubulin of A. castellanii (Genbank accession no: XP_004353728) was included as housekeeping gene for data normalisation. PCR mixtures were also analyzed by electrophoresis for amplicons detection. All statistical analyses were performed using the paired one-tailed Student’s t test. Results: Our pathogenicity tests showed that the virulence-reactivated Acanthamoeba had a higher degree of cytopathic effect on vero cells, a better resistance to encystment challenge and a higher gelatinolytic activity which was catalysed by serine protease. qPCR assay showed that DNMT1 expression was significantly higher in the virulence-reactivated compared to the virulence-attenuated Acanthamoeba strain (p ≤ 0.01). The specificity of primers which targeted on DNMT1 was confirmed by sequence analysis of PCR amplicons, which showed a 97% similarity to the published DNA-methyltransferase gene of A. castellanii (GenBank accession no: XM_004332804.1). Out of the five primer pairs which targeted on the HDAC family genes, only HDAC4 expression was significantly difference between the two variant strains. In contrast to DNMT1, HDAC4 expression was much higher in the virulence-attenuated Acanthamoeba strain. Conclusion: Our mouse passages had successfully restored the virulence of the attenuated strain. Our findings suggested that DNA-methyltransferase (DNMT1) and histone deacetylase (HDAC4) expressions are associated with virulence potential of Acanthamoeba spp.

Keywords: acanthamoeba, DNA-methyltransferase, histone deacetylase, virulence-associated proteins

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88 Red Dawn in the Desert: A World-Systems Analysis of the Maritime Silk Road Initiative

Authors: Toufic Sarieddine

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The current debate on the hegemonic impact of China’s Belt and Road Initiative (BRI) is of two opposing strands: Resilient and absolute US hegemony on the one hand and various models of multipolar hegemony such as bifurcation on the other. Bifurcation theories illustrate an unprecedented division of hegemonic functions between China and the US, whereby Beijing becomes the world’s economic hegemon, leaving Washington the world’s military hegemon and security guarantor. While consensus points to China being the main driver of unipolarity’s rupturing, the debate among bifurcationists is on the location of the first rupture. In this regard, the Middle East and North Africa (MENA) region has seen increasing Chinese foreign direct investment in recent years while that to other regions has declined, ranking it second in 2018 as part of the financing for the Maritime Silk Road Initiative (MSRI). China has also become the top trade partner of 11 states in the MENA region, as well as its top source of machine imports, surpassing the US and achieving an overall trade surplus almost double that of Washington’s. These are among other features outlined in world-systems analysis (WSA) literature which correspond with the emergence of a new hegemon. WSA is further utilized to gauge other facets of China’s increasing involvement in MENA and assess whether bifurcation is unfolding therein. These features of hegemony include the adoption of China’s modi operandi, economic dominance in production, trade, and finance, military capacity, cultural hegemony in ideology, education, and language, and the promotion of a general interest around which to rally potential peripheries (MENA states in this case). China’s modi operandi has seen some adoption with regards to support against the United Nations Convention on the Law of the Sea, oil bonds denominated in the yuan, and financial institutions such as the Shanghai Gold Exchange enjoying increasing Arab patronage. However, recent elections in Qatar, as well as liberal reforms in Saudi Arabia, demonstrate Washington’s stronger normative influence. Meanwhile, Washington’s economic dominance is challenged by China’s sizable machine exports, increasing overall imports, and widening trade surplus, but retains some clout via dominant arms and transport exports, as well as free-trade deals across the region. Militarily, Washington bests Beijing’s arms exports, has a dominant and well-established presence in the region, and successfully blocked Beijing’s attempt to penetrate through the UAE. Culturally, Beijing enjoys higher favorability in Arab public opinion, and its broadcast networks have found some resonance with Arab audiences. In education, the West remains MENA students’ preferred destination. Further, while Mandarin has become increasingly available in schools across MENA, its usage and availability still lag far behind English. Finally, Beijing’s general interest in infrastructure provision and prioritizing economic development over social justice and democracy provides an avenue for increased incorporation between Beijing and the MENA region. The overall analysis shows solid progress towards bifurcation in MENA.

Keywords: belt and road initiative, hegemony, Middle East and North Africa, world-systems analysis

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87 Early Impact Prediction and Key Factors Study of Artificial Intelligence Patents: A Method Based on LightGBM and Interpretable Machine Learning

Authors: Xingyu Gao, Qiang Wu

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Patents play a crucial role in protecting innovation and intellectual property. Early prediction of the impact of artificial intelligence (AI) patents helps researchers and companies allocate resources and make better decisions. Understanding the key factors that influence patent impact can assist researchers in gaining a better understanding of the evolution of AI technology and innovation trends. Therefore, identifying highly impactful patents early and providing support for them holds immeasurable value in accelerating technological progress, reducing research and development costs, and mitigating market positioning risks. Despite the extensive research on AI patents, accurately predicting their early impact remains a challenge. Traditional methods often consider only single factors or simple combinations, failing to comprehensively and accurately reflect the actual impact of patents. This paper utilized the artificial intelligence patent database from the United States Patent and Trademark Office and the Len.org patent retrieval platform to obtain specific information on 35,708 AI patents. Using six machine learning models, namely Multiple Linear Regression, Random Forest Regression, XGBoost Regression, LightGBM Regression, Support Vector Machine Regression, and K-Nearest Neighbors Regression, and using early indicators of patents as features, the paper comprehensively predicted the impact of patents from three aspects: technical, social, and economic. These aspects include the technical leadership of patents, the number of citations they receive, and their shared value. The SHAP (Shapley Additive exPlanations) metric was used to explain the predictions of the best model, quantifying the contribution of each feature to the model's predictions. The experimental results on the AI patent dataset indicate that, for all three target variables, LightGBM regression shows the best predictive performance. Specifically, patent novelty has the greatest impact on predicting the technical impact of patents and has a positive effect. Additionally, the number of owners, the number of backward citations, and the number of independent claims are all crucial and have a positive influence on predicting technical impact. In predicting the social impact of patents, the number of applicants is considered the most critical input variable, but it has a negative impact on social impact. At the same time, the number of independent claims, the number of owners, and the number of backward citations are also important predictive factors, and they have a positive effect on social impact. For predicting the economic impact of patents, the number of independent claims is considered the most important factor and has a positive impact on economic impact. The number of owners, the number of sibling countries or regions, and the size of the extended patent family also have a positive influence on economic impact. The study primarily relies on data from the United States Patent and Trademark Office for artificial intelligence patents. Future research could consider more comprehensive data sources, including artificial intelligence patent data, from a global perspective. While the study takes into account various factors, there may still be other important features not considered. In the future, factors such as patent implementation and market applications may be considered as they could have an impact on the influence of patents.

Keywords: patent influence, interpretable machine learning, predictive models, SHAP

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86 Functional Plasma-Spray Ceramic Coatings for Corrosion Protection of RAFM Steels in Fusion Energy Systems

Authors: Chen Jiang, Eric Jordan, Maurice Gell, Balakrishnan Nair

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Nuclear fusion, one of the most promising options for reliably generating large amounts of carbon-free energy in the future, has seen a plethora of ground-breaking technological advances in recent years. An efficient and durable “breeding blanket”, needed to ensure a reactor’s self-sufficiency by maintaining the optimal coolant temperature as well as by minimizing radiation dosage behind the blanket, still remains a technological challenge for the various reactor designs for commercial fusion power plants. A relatively new dual-coolant lead-lithium (DCLL) breeder design has exhibited great potential for high-temperature (>700oC), high-thermal-efficiency (>40%) fusion reactor operation. However, the structural material, namely reduced activation ferritic-martensitic (RAFM) steel, is not chemically stable in contact with molten Pb-17%Li coolant. Thus, to utilize this new promising reactor design, the demand for effective corrosion-resistant coatings on RAFM steels represents a pressing need. Solution Spray Technologies LLC (SST) is developing a double-layer ceramic coating design to address the corrosion protection of RAFM steels, using a novel solution and solution/suspension plasma spray technology through a US Department of Energy-funded project. Plasma spray is a coating deposition method widely used in many energy applications. Novel derivatives of the conventional powder plasma spray process, known as the solution-precursor and solution/suspension-hybrid plasma spray process, are powerful methods to fabricate thin, dense ceramic coatings with complex compositions necessary for the corrosion protection in DCLL breeders. These processes can be used to produce ultra-fine molten splats and to allow fine adjustment of coating chemistry. Thin, dense ceramic coatings with chosen chemistry for superior chemical stability in molten Pb-Li, low activation properties, and good radiation tolerance, is ideal for corrosion-protection of RAFM steels. A key challenge is to accommodate its CTE mismatch with the RAFM substrate through the selection and incorporation of appropriate bond layers, thus allowing for enhanced coating durability and robustness. Systematic process optimization is being used to define the optimal plasma spray conditions for both the topcoat and bond-layer, and X-ray diffraction and SEM-EDS are applied to successfully validate the chemistry and phase composition of the coatings. The plasma-sprayed double-layer corrosion resistant coatings were also deposited onto simulated RAFM steel substrates, which are being tested separately under thermal cycling, high-temperature moist air oxidation as well as molten Pb-Li capsule corrosion conditions. Results from this testing on coated samples, and comparisons with bare RAFM reference samples will be presented and conclusions will be presented assessing the viability of the new ceramic coatings to be viable corrosion prevention systems for DCLL breeders in commercial nuclear fusion reactors.

Keywords: breeding blanket, corrosion protection, coating, plasma spray

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85 Organisational Mindfulness Case Study: A 6-Week Corporate Mindfulness Programme Significantly Enhances Organisational Well-Being

Authors: Dana Zelicha

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A 6-week mindfulness programme was launched to improve the well being and performance of 20 managers (including the supervisor) of an international corporation in London. A unique assessment methodology was customised to the organisation’s needs, measuring four parameters: prioritising skills, listening skills, mindfulness levels and happiness levels. All parameters showed significant improvements (p < 0.01) post intervention, with a remarkable increase in listening skills and mindfulness levels. Although corporate mindfulness programmes have proven to be effective, the challenge remains the low engagement levels at home and the implementation of these tools beyond the scope of the intervention. This study has offered an innovative approach to enforce home engagement levels, which yielded promising results. The programme launched with a 2-day introduction intervention, which was followed by a 6-week training course (1 day a week; 2 hours each). Participants learned all basic principles of mindfulness such as mindfulness meditations, Mindfulness Based Stress Reduction (MBSR) techniques and Mindfulness Based Cognitive Therapy (MBCT) practices to incorporate into their professional and personal lives. The programme contained experiential mindfulness meditations and innovative mindfulness tools (OWBA-MT) created by OWBA - The Well Being Agency. Exercises included Mindful Meetings, Unitasking and Mindful Feedback. All sessions concluded with guided discussions and group reflections. One fundamental element of this programme was engagement level outside of the workshop. In the office, participants connected with a mindfulness buddy - a team member in the group with whom they could find support throughout the programme. At home, participants completed online daily mindfulness forms that varied according to weekly themes. These customised forms gave participants the opportunity to reflect on whether they made time for daily mindfulness practice, and to facilitate a sense of continuity and responsibility. At the end of the programme, the most engaged team member was crowned the ‘mindful maven’ and received a special gift. The four parameters were measured using online self-reported questionnaires, including the Listening Skills Inventory (LSI), Mindfulness Attention Awareness Scale (MAAS), Time Management Behaviour Scale (TMBS) and a modified version of the Oxford Happiness Questionnaire (OHQ). Pre-intervention questionnaires were collected at the start of the programme, and post-intervention data was collected 4-weeks following completion. Quantitative analysis using paired T-tests of means showed significant improvements, with a 23% increase in listening skills, a 22% improvement in mindfulness levels, a 12% increase in prioritising skills, and an 11% improvement in happiness levels. Participant testimonials exhibited high levels of satisfaction and the overall results indicate that the mindfulness programme substantially impacted the team. These results suggest that 6-week mindfulness programmes can improve employees’ capacities to listen and work well with others, to effectively manage time and to experience enhanced satisfaction both at work and in life. Limitations noteworthy to consider include the afterglow effect and lack of generalisability, as this study was conducted on a small and fairly homogenous sample.

Keywords: corporate mindfulness, listening skills, organisational well being, prioritising skills, mindful leadership

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84 Deconstructing Reintegration Services for Survivors of Human Trafficking: A Feminist Analysis of Australian and Thai Government and Non-Government Responses

Authors: Jessica J. Gillies

Abstract:

Awareness of the tragedy that is human trafficking has increased exponentially over the past two decades. The four pillars widely recognised as global solutions to the problem are prevention, prosecution, protection, and partnership between government and non-government organisations. While ‘sex-trafficking’ initially received major attention, this focus has shifted to other industries that conceal broader experiences of exploitation. However, within the regions of focus for this study, namely Australia and Thailand, trafficking for the purpose of sexual exploitation remains the commonly uncovered narrative of criminal justice investigations. In these regions anti-trafficking action is characterised by government-led prevention and prosecution efforts; whereas protection and reintegration practices have received criticism. Typically, non-government organisations straddle the critical chasm between policy and practice; therefore, they are perfectly positioned to contribute valuable experiential knowledge toward understanding how both sectors can support survivors in the post-trafficking experience. The aim of this research is to inform improved partnerships throughout government and non-government post-trafficking services by illuminating gaps in protection and reintegration initiatives. This research will explore government and non-government responses to human trafficking in Thailand and Australia, in order to understand how meaning is constructed in this context and how the construction of meaning effects survivors in the post-trafficking experience. A qualitative, three-stage methodology was adopted for this study. The initial stage of enquiry consisted of a discursive analysis, in order to deconstruct the broader discourses surrounding human trafficking. The data included empirical papers, grey literature such as publicly available government and non-government reports, and anti-trafficking policy documents. The second and third stages of enquiry will attempt to further explore the findings of the discourse analysis and will focus more specifically on protection and reintegration in Australia and Thailand. Stages two and three will incorporate process observations in government and non-government survivor support services, and semi-structured interviews with employees and volunteers within these settings. Two key findings emerged from the discursive analysis. The first exposed conflicting feminist arguments embedded throughout anti-trafficking discourse. Informed by conflicting feminist discourses on sex-work, a discursive relationship has been constructed between sex-industry policy and anti-trafficking policy. In response to this finding, data emerging from the process observations and semi-structured interviews will be interpreted using a feminist theoretical framework. The second finding progresses from the construction in the first. The discursive construction of sex-trafficking appears to have had influence over perceptions of the legitimacy of survivors, and therefore the support they receive in the post-trafficking experience. For example; women who willingly migrate for employment in the sex-industry, and on arrival are faced with exploitative conditions, are not perceived to be deserving of the same support as a woman who is not coerced, but rather physically forced, into such circumstances, yet both meet the criteria for a victim of human trafficking. The forthcoming study is intended to contribute toward building knowledge and understanding around the implications of the construction of legitimacy; and contextualise this in reference to government led protection and reintegration support services for survivors in the post-trafficking experience.

Keywords: Australia, government, human trafficking, non-government, reintegration, Thailand

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83 Amyloid Angiopathy and Golf: Two Opposite but Close Worlds

Authors: Andrea Bertocchi, Alessio Barnaba Di Fonzo, Davide Talarico, Simone Rivaroli, Jeff Konin

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The patient is a 89 years old male (180cm/85kg) retired notary former golfer with no past medical history. He describes a progressive ideomotor slowdown for 14 months. The disorder is characterized by short-term memory deficits and, for some months, also by unstable walking with a broad base with skidding and risk of falling at directional changes and urinary urgency. There were also episodes of aggression towards his wife and staff. At the time, the patient takes no prescribed medications. He has difficulty eating, dressing, and some problems with personal hygiene. In the initial visit, the patient was alert, cooperating, and performed simple tasks; however, he has a hearing impairment, slowed spontaneous speech, and amnestic deficit to the short story. Ideomotor apraxia is not present. He scored 20 points in the MMSE. From a motor function, he has deficits using Medical Research Council (MRC) 3-/5 in bilateral lower limbs and requires maximum assistance from sit to stand with existing premature fatigue. He’s unable to walk for about 1 month. Tremors and hypertonia are absent. BERG was unable to be administered, and BARTHEL was obtained 45/100. An Amyloid Angiopathy is suspected and then confirmed at the neurological examination. Therehabilitation objectives were the recovery of mobility and reinforcement of the UE/LE, especially legs, for recovery of standing and walking. The cognitive aspect was also an essential factor for the patient's recovery. The literature doesn’t demonstrate any particular studies regarding motor and cognitive rehabilitation on this pathology. Failing to manage his attention on exercise and tending to be disinterested and falling asleep constantly, we used golf-specific gestures to stimulate his mind to work and get results because the patient has memory recall of golf related movement. We worked for 4 months with a frequency of 3 sessions per week. Every session lasted for 45 minutes. After 4 months of work, the patient walked independently with the use of a stick for about 120 meters without stopping. MRC 4/5 AI bilaterally andpostural steps performed independently with supervision. BERG 36/56. BARTHEL 65/100. 6 Minutes Walking Test (6MWT), at the beginning, it wasn’t measurable, now, he performs 151,5m with Numeric Rating Scale 4 at the beginning and 7 at the end. Cognitively, he no longer has episodes of aggression, although the short-term memory and concentration deficit remains. Amyloid Angiopathy is a mix of motor and cognitive disorder. It is worth the thought that cerebral amyloid angiopathy manifests with functional deficits due to strokes and bleedings and, as such, has an important rehabilitation indication, as classical stroke is not associated with amyloidosis. Exploring the motor patterns learned at a young age and remained in the implicit and explicit memory of the patient allowed us to set up effective work and to obtain significant results in the short-middle term. Surely many studies will still be done regarding this pathology and its rehabilitation, but the importance of the cognitive sphere applied to the motor sphere could represent an important starting point.

Keywords: amyloid angiopathy, cognitive rehabilitation, golf, motor disorder

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82 Transcriptional Differences in B cell Subpopulations over the Course of Preclinical Autoimmunity Development

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

Abstract:

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.

Keywords:

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81 Rethinking Urban Voids: An Investigation beneath the Kathipara Flyover, Chennai into a Transit Hub by Adaptive Utilization of Space

Authors: V. Jayanthi

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Urbanization and pace of urbanization have increased tremendously in last few decades. More towns are now getting converted into cities. Urbanization trend is seen all over the world but is becoming most dominant in Asia. Today, the scale of urbanization in India is so huge that Indian cities are among the fastest-growing in the world, including Bangalore, Hyderabad, Pune, Chennai, Delhi, and Mumbai. Urbanization remains a single predominant factor that is continuously linked to the destruction of urban green spaces. With reference to Chennai as a case study, which is suffering from rapid deterioration of its green spaces, this paper sought to fill this gap by exploring key factors aside urbanization that is responsible for the destruction of green spaces. The paper relied on a research approach and triangulated data collection techniques such as interviews, focus group discussion, personal observation and retrieval of archival data. It was observed that apart from urbanization, problem of ownership of green space lands, low priority to green spaces, poor maintenance, enforcement of development controls, wastage of underpass spaces, and uncooperative attitudes of the general public, play a critical role in the destruction of urban green spaces. Therefore the paper narrows down to a point, that for a city to have a proper sustainable urban green space, broader city development plans are essential. Though rapid urbanization is an indicator of positive development, it is also accompanied by a host of challenges. Chennai lost a lot of greenery, as the city urbanized rapidly that led to a steep fall in vegetation cover. Environmental deterioration will be the big price we pay if Chennai continues to grow at the expense of greenery. Soaring skyscrapers, multistoried complexes, gated communities, and villas, frame the iconic skyline of today’s Chennai city which reveals that we overlook the importance of our green cover, which is important to balance our urban and lung spaces. Chennai, with a clumped landscape at the center of the city, is predicted to convert 36% of its total area into urban areas by 2026. One major issue is that a city designed and planned in isolation creates underused spaces all around the cities which are of negligence. These urban voids are dead, underused, unused spaces in the cities that are formed due to inefficient decision making, poor land management, and poor coordination. Urban voids have huge potential of creating a stronger urban fabric, exploited as public gathering spaces, pocket parks or plazas or just enhance public realm, rather than dumping of debris and encroachments. Flyovers need to justify their existence themselves by being more than just traffic and transport solutions. The vast, unused space below the Kathipara flyover is a case in point. This flyover connects three major routes: Tambaram, Koyambedu, and Adyar. This research will focus on the concept of urban voids, how these voids under the flyovers, can be used for place making process, how this space beneath flyovers which are neglected, can be a part of the urban realm through urban design and landscaping.

Keywords: landscape design, flyovers, public spaces, reclaiming lost spaces, urban voids

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80 Accurate Energy Assessment Technique for Mine-Water District Heat Network

Authors: B. Philip, J. Littlewood, R. Radford, N. Evans, T. Whyman, D. P. Jones

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UK buildings and energy infrastructures are heavily dependent on natural gas, a large proportion of which is used for domestic space heating. However, approximately half of the gas consumed in the UK is imported. Improving energy security and reducing carbon emissions are major government drivers for reducing gas dependency. In order to do so there needs to be a wholesale shift in the energy provision to householders without impacting on thermal comfort levels, convenience or cost of supply to the end user. Heat pumps are seen as a potential alternative in modern well insulated homes, however, can the same be said of older homes? A large proportion of housing stock in Britain was built prior to 1919. The age of the buildings bears testimony to the quality of construction; however, their thermal performance falls far below the minimum currently set by UK building standards. In recent years significant sums of money have been invested to improve energy efficiency and combat fuel poverty in some of the most deprived areas of Wales. Increasing energy efficiency of older properties remains a significant challenge, which cannot be achieved through insulation and air-tightness interventions alone, particularly when alterations to historically important architectural features of the building are not permitted. This paper investigates the energy demand of pre-1919 dwellings in a former Welsh mining village, the feasibility of meeting that demand using water from the disused mine workings to supply a district heat network and potential barriers to success of the scheme. The use of renewable solar energy generation and storage technologies, both thermal and electrical, to reduce the load and offset increased electricity demand, are considered. A wholistic surveying approach to provide a more accurate assessment of total household heat demand is proposed. Several surveying techniques, including condition surveys, air permeability, heat loss calculations, and thermography were employed to provide a clear picture of energy demand. Additional insulation can bring unforeseen consequences which are detrimental to the fabric of the building, potentially leading to accelerated dilapidation of the asset being ‘protected’. Increasing ventilation should be considered in parallel, to compensate for the associated reduction in uncontrolled infiltration. The effectiveness of thermal performance improvements are demonstrated and the detrimental effects of incorrect material choice and poor installation are highlighted. The findings show estimated heat demand to be in close correlation to household energy bills. Major areas of heat loss were identified such that improvements to building thermal performance could be targeted. The findings demonstrate that the use of heat pumps in older buildings is viable, provided sufficient improvement to thermal performance is possible. Addition of passive solar thermal and photovoltaic generation can help reduce the load and running cost for the householder. The results were used to predict future heat demand following energy efficiency improvements, thereby informing the size of heat pumps required.

Keywords: heat demand, heat pump, renewable energy, retrofit

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79 An Infrared Inorganic Scintillating Detector Applied in Radiation Therapy

Authors: Sree Bash Chandra Debnath, Didier Tonneau, Carole Fauquet, Agnes Tallet, Julien Darreon

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Purpose: Inorganic scintillating dosimetry is the most recent promising technique to solve several dosimetric issues and provide quality assurance in radiation therapy. Despite several advantages, the major issue of using scintillating detectors is the Cerenkov effect, typically induced in the visible emission range. In this context, the purpose of this research work is to evaluate the performance of a novel infrared inorganic scintillator detector (IR-ISD) in the radiation therapy treatment to ensure Cerenkov free signal and the best matches between the delivered and prescribed doses during treatment. Methods: A simple and small-scale infrared inorganic scintillating detector of 100 µm diameter with a sensitive scintillating volume of 2x10-6 mm3 was developed. A prototype of the dose verification system has been introduced based on PTIR1470/F (provided by Phosphor Technology®) material used in the proposed novel IR-ISD. The detector was tested on an Elekta LINAC system tuned at 6 MV/15MV and a brachytherapy source (Ir-192) used in the patient treatment protocol. The associated dose rate was measured in count rate (photons/s) using a highly sensitive photon counter (sensitivity ~20ph/s). Overall measurements were performed in IBATM water tank phantoms by following international Technical Reports series recommendations (TRS 381) for radiotherapy and TG43U1 recommendations for brachytherapy. The performance of the detector was tested through several dosimetric parameters such as PDD, beam profiling, Cerenkov measurement, dose linearity, dose rate linearity repeatability, and scintillator stability. Finally, a comparative study is also shown using a reference microdiamond dosimeter, Monte-Carlo (MC) simulation, and data from recent literature. Results: This study is highlighting the complete removal of the Cerenkov effect especially for small field radiation beam characterization. The detector provides an entire linear response with the dose in the 4cGy to 800 cGy range, independently of the field size selected from 5 x 5 cm² down to 0.5 x 0.5 cm². A perfect repeatability (0.2 % variation from average) with day-to-day reproducibility (0.3% variation) was observed. Measurements demonstrated that ISD has superlinear behavior with dose rate (R2=1) varying from 50 cGy/s to 1000 cGy/s. PDD profiles obtained in water present identical behavior with a build-up maximum depth dose at 15 mm for different small fields irradiation. A low dimension of 0.5 x 0.5 cm² field profiles have been characterized, and the field cross profile presents a Gaussian-like shape. The standard deviation (1σ) of the scintillating signal remains within 0.02% while having a very low convolution effect, thanks to lower sensitive volume. Finally, during brachytherapy, a comparison with MC simulations shows that considering energy dependency, measurement agrees within 0.8% till 0.2 cm source to detector distance. Conclusion: The proposed scintillating detector in this study shows no- Cerenkov radiation and efficient performance for several radiation therapy measurement parameters. Therefore, it is anticipated that the IR-ISD system can be promoted to validate with direct clinical investigations, such as appropriate dose verification and quality control in the Treatment Planning System (TPS).

Keywords: IR-Scintillating detector, dose measurement, micro-scintillators, Cerenkov effect

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78 Kinematic Gait Analysis Is a Non-Invasive, More Objective and Earlier Measurement of Impairment in the Mdx Mouse Model of Duchenne Muscular Dystrophy

Authors: P. J. Sweeney, T. Ahtoniemi, J. Puoliväli, T. Laitinen, K. Lehtimäki, A. Nurmi, D. Wells

Abstract:

Duchenne muscular dystrophy (DMD) is caused by an X linked mutation in the dystrophin gene; lack of dystrophin causes a progressive muscle necrosis which leads to a progressive decrease in mobility in those suffering from the disease. The MDX mouse, a mutant mouse model which displays a frank dystrophinopathy, is currently widely employed in pre clinical efficacy models for treatments and therapies aimed at DMD. In general the end-points examined within this model have been based on invasive histopathology of muscles and serum biochemical measures like measurement of serum creatine kinase (sCK). It is established that a “critical period” between 4 and 6 weeks exists in the MDX mouse when there is extensive muscle damage that is largely sub clinical but evident with sCK measurements and histopathological staining. However, a full characterization of the MDX model remains largely incomplete especially with respect to the ability to aggravate of the muscle damage beyond the critical period. The purpose of this study was to attempt to aggravate the muscle damage in the MDX mouse and to create a wider, more readily translatable and discernible, therapeutic window for the testing of potential therapies for DMD. The study consisted of subjecting 15 male mutant MDX mice and 15 male wild-type mice to an intense chronic exercise regime that consisted of bi-weekly (two times per week) treadmill sessions over a 12 month period. Each session was 30 minutes in duration and the treadmill speed was gradually built up to 14m/min for the entire session. Baseline plasma creatine kinase (pCK), treadmill training performance and locomotor activity were measured after the “critical period” at around 10 weeks of age and again at 14 weeks of age, 6 months, 9 months and 12 months of age. In addition, kinematic gait analysis was employed using a novel analysis algorithm in order to compare changes in gait and fine motor skills in diseased exercised MDX mice compared to exercised wild type mice and non exercised MDX mice. In addition, a morphological and metabolic profile (including lipid profile), from the muscles most severely affected, the gastrocnemius muscle and the tibialis anterior muscle, was also measured at the same time intervals. Results indicate that by aggravating or exacerbating the underlying muscle damage in the MDX mouse by exercise a more pronounced and severe phenotype in comes to light and this can be picked up earlier by kinematic gait analysis. A reduction in mobility as measured by open field is not apparent at younger ages nor during the critical period, but changes in gait are apparent in the mutant MDX mice. These gait changes coincide with pronounced morphological and metabolic changes by non-invasive anatomical MRI and proton spectroscopy (1H-MRS) we have reported elsewhere. Evidence of a progressive asymmetric pathology in imaging parameters as well as in the kinematic gait analysis was found. Taken together, the data show that chronic exercise regime exacerbates the muscle damage beyond the critical period and the ability to measure through non-invasive means are important factors to consider when performing preclinical efficacy studies in the MDX mouse.

Keywords: Gait, muscular dystrophy, Kinematic analysis, neuromuscular disease

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77 Simulation-based Decision Making on Intra-hospital Patient Referral in a Collaborative Medical Alliance

Authors: Yuguang Gao, Mingtao Deng

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The integration of independently operating hospitals into a unified healthcare service system has become a strategic imperative in the pursuit of hospitals’ high-quality development. Central to the concept of group governance over such transformation, exemplified by a collaborative medical alliance, is the delineation of shared value, vision, and goals. Given the inherent disparity in capabilities among hospitals within the alliance, particularly in the treatment of different diseases characterized by Disease Related Groups (DRG) in terms of effectiveness, efficiency and resource utilization, this study aims to address the centralized decision-making of intra-hospital patient referral within the medical alliance to enhance the overall production and quality of service provided. We first introduce the notion of production utility, where a higher production utility for a hospital implies better performance in treating patients diagnosed with that specific DRG group of diseases. Then, a Discrete-Event Simulation (DES) framework is established for patient referral among hospitals, where patient flow modeling incorporates a queueing system with fixed capacities for each hospital. The simulation study begins with a two-member alliance. The pivotal strategy examined is a "whether-to-refer" decision triggered when the bed usage rate surpasses a predefined threshold for either hospital. Then, the decision encompasses referring patients to the other hospital based on DRG groups’ production utility differentials as well as bed availability. The objective is to maximize the total production utility of the alliance while minimizing patients’ average length of stay and turnover rate. Thus the parameter under scrutiny is the bed usage rate threshold, influencing the efficacy of the referral strategy. Extending the study to a three-member alliance, which could readily be generalized to multi-member alliances, we maintain the core setup while introducing an additional “which-to-refer" decision that involves referring patients with specific DRG groups to the member hospital according to their respective production utility rankings. The overarching goal remains consistent, for which the bed usage rate threshold is once again a focal point for analysis. For the two-member alliance scenario, our simulation results indicate that the optimal bed usage rate threshold hinges on the discrepancy in the number of beds between member hospitals, the distribution of DRG groups among incoming patients, and variations in production utilities across hospitals. Transitioning to the three-member alliance, we observe similar dependencies on these parameters. Additionally, it becomes evident that an imbalanced distribution of DRG diagnoses and further disparity in production utilities among member hospitals may lead to an increase in the turnover rate. In general, it was found that the intra-hospital referral mechanism enhances the overall production utility of the medical alliance compared to individual hospitals without partnership. Patients’ average length of stay is also reduced, showcasing the positive impact of the collaborative approach. However, the turnover rate exhibits variability based on parameter setups, particularly when patients are redirected within the alliance. In conclusion, the re-structuring of diagnostic disease groups within the medical alliance proves instrumental in improving overall healthcare service outcomes, providing a compelling rationale for the government's promotion of patient referrals within collaborative medical alliances.

Keywords: collaborative medical alliance, disease related group, patient referral, simulation

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