Search results for: new demand control ventilation (nDCV)

Authors: Leander Van Neste, Kirk Wojno

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The innate immune system reacts to foreign insult in several unique ways, one of which is phagocytosis of perceived threats such as cancer, bacteria, and viruses. The goal of this study was to look for evidence of phagocytosed RNA from tumor cells in circulating monocytes. While all monocytes possess phagocytic capabilities, the non-classical CD14+/FCGR3A+ monocytes and the intermediate CD14++/FCGR3A+ monocytes most actively remove threatening ‘external’ cellular materials. Purified CD14-positive monocyte samples from fourteen patients recently diagnosed with clinically localized prostate cancer (PCa) were investigated by single-cell RNA sequencing using the 10X Genomics protocol followed by paired-end sequencing on Illumina’s NovaSeq. Similarly, samples were processed and used as controls, i.e., one patient underwent biopsy but was found not to harbor prostate cancer (benign), three young, healthy men, and three men previously diagnosed with prostate cancer that recently underwent (curative) radical prostatectomy (post-RP). Sequencing data were mapped using 10X Genomics’ CellRanger software and viable cells were subsequently identified using CellBender, removing technical artifacts such as doublets and non-cellular RNA. Next, data analysis was performed in R, using the Seurat package. Because the main goal was to identify differences between PCa patients and ‘control’ patients, rather than exploring differences between individual subjects, the individual Seurat objects of all 21 patients were merged into one Seurat object per Seurat’s recommendation. Finally, the single-cell dataset was normalized as a whole prior to further analysis. Cell identity was assessed using the SingleR and cell dex packages. The Monaco Immune Data was selected as the reference dataset, consisting of bulk RNA-seq data of sorted human immune cells. The Monaco classification was supplemented with normalized PCa data obtained from The Cancer Genome Atlas (TCGA), which consists of bulk RNA sequencing data from 499 prostate tumor tissues (including 1 metastatic) and 52 (adjacent) normal prostate tissues. SingleR was subsequently run on the combined immune cell and PCa datasets. As expected, the vast majority of cells were labeled as having a monocytic origin (~90%), with the most noticeable difference being the larger number of intermediate monocytes in the PCa patients (13.6% versus 7.1%; p<.001). In men harboring PCa, 0.60% of all purified monocytes were classified as harboring PCa signals when the TCGA data were included. This was 3-fold, 7.5-fold, and 4-fold higher compared to post-RP, benign, and young men, respectively (all p<.001). In addition, with 7.91%, the number of unclassified cells, i.e., cells with pruned labels due to high uncertainty of the assigned label, was also highest in men with PCa, compared to 3.51%, 2.67%, and 5.51% of cells in post-RP, benign, and young men, respectively (all p<.001). It can be postulated that actively phagocytosing cells are hardest to classify due to their dual immune cell and foreign cell nature. Hence, the higher number of unclassified cells and intermediate monocytes in PCa patients might reflect higher phagocytic activity due to tumor burden. This also illustrates that small numbers (~1%) of circulating peripheral blood monocytes that have interacted with tumor cells might still possess detectable phagocytosed tumor RNA.

Keywords: circulating monocytes, phagocytic cells, prostate cancer, tumor immune response

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Authors: Naghmeh M. Bandari, Javad Dargahi, Muthukumaran Packirisamy

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Robot-assisted minimally invasive surgery (RMIS) has been widely performed around the world during the last two decades. RMIS demonstrates significant advantages over conventional surgery, e.g., improving the accuracy and dexterity of a surgeon, providing 3D vision, motion scaling, hand-eye coordination, decreasing tremor, and reducing x-ray exposure for surgeons. Despite benefits, surgeons cannot touch the surgical site and perceive tactile information. This happens due to the remote control of robots. The literature survey identified the lack of force feedback as the riskiest limitation in the existing technology. Without the perception of tool-tissue contact force, the surgeon might apply an excessive force causing tissue laceration or insufficient force causing tissue slippage. The primary use of force sensors has been to measure the tool-tissue interaction force in real-time in-situ. Design of a tactile sensor is subjected to a set of design requirements, e.g., biocompatibility, electrical-passivity, MRI-compatibility, miniaturization, ability to measure static and dynamic force. In this study, a planar optical fiber-based sensor was proposed to mount at the surgical grasper. It was developed based on the light intensity modulation principle. The deflectable part of the sensor was a beam modeled as a cantilever Euler-Bernoulli beam on rigid substrates. A semi-cylindrical indenter was attached to the bottom surface the beam at the mid-span. An optical fiber was secured at both ends on the same rigid substrates. The indenter was in contact with the fiber. External force on the sensor caused deflection in the beam and optical fiber simultaneously. The micro-bending of the optical fiber would consequently result in light power loss. The sensor was simulated and studied using finite element methods. A laser light beam with 800nm wavelength and 5mW power was used as the input to the optical fiber. The output power was measured using a photodetector. The voltage from photodetector was calibrated to the external force for a chirp input (0.1-5Hz). The range, resolution, and hysteresis of the sensor were studied under monotonic and harmonic external forces of 0-2.0N with 0 and 5Hz, respectively. The results confirmed the validity of proposed sensing principle. Also, the sensor demonstrated an acceptable linearity (R2 > 0.9). A minimum external force was observed below which no power loss was detectable. It is postulated that this phenomenon is attributed to the critical angle of the optical fiber to observe total internal reflection. The experimental results were of negligible hysteresis (R2 > 0.9) and in fair agreement with the simulations. In conclusion, the suggested planar sensor is assessed to be a cost-effective solution, feasible, and easy to use the sensor for being miniaturized and integrated at the tip of robotic graspers. Geometrical and optical factors affecting the minimum sensible force and the working range of the sensor should be studied and optimized. This design is intrinsically scalable and meets all the design requirements. Therefore, it has a significant potential of industrialization and mass production.

Keywords: force sensor, minimally invasive surgery, optical sensor, robotic surgery, tactile sensor

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Authors: Paola Clerici Maestosi

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Positive Energy District (PED) is a rather recent concept whose aim is to contribute to the main objectives of the Energy Union strategy. It is based on an integrated multi-sectoral approach in response to Europe's most complex challenges. PED integrates energy efficiency, renewable energy production, and energy flexibility in an integrated, multi-sectoral approach at the city level. The core idea behind Positive Energy Districts (PEDs) is to establish an urban area that can generate more energy than it consumes. Additionally, it should be flexible enough to adapt to changes in the energy market. This is crucial because a PED's goal is not just to achieve an annual surplus of net energy but also to help reduce the impact on the interconnected centralized energy networks. It achieves this by providing options to increase on-site load matching and self-consumption, employing technologies for short- and long-term energy storage, and offering energy flexibility through smart control. Thus, it seems that PEDs can encompass all types of buildings in the city environment. Given this which is the added value of having green buildings being constitutive part of PEDS? The paper will present a systematic literature review identifying the role of green building in Positive Energy District to provide answer to following questions: (RQ1) the state of the art of PEDs implementation; (RQ2) penetration of green building in Positive Energy District selected case studies. Methodological approach is based on a broad holistic study of bibliographic sources according to Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) further data will be analysed, mapped and text mining through VOSviewer. Main contribution of research is a cognitive framework on Positive Energy District in Europe and a selection of case studies where green building supported the transition to PED. The inclusion of green buildings within Positive Energy Districts (PEDs) adds significant value for several reasons. Firstly, green buildings are designed and constructed with a focus on environmental sustainability, incorporating energy-efficient technologies, materials, and design principles. As integral components of PEDs, these structures contribute directly to the district's overall ability to generate more energy than it consumes. Secondly, green buildings typically incorporate renewable energy sources, such as solar panels or wind turbines, further boosting the district's capacity for energy generation. This aligns with the PED objective of achieving a surplus of net energy. Moreover, green buildings often feature advanced systems for on-site energy management, load-matching, and self-consumption. This enhances the PED's capability to respond to variations in the energy market, making the district more agile and flexible in optimizing energy use. Additionally, the environmental considerations embedded in green buildings align with the broader sustainability goals of PEDs. By reducing the ecological footprint of individual structures, PEDs with green buildings contribute to minimizing the overall impact on centralized energy networks and promote a more sustainable urban environment. In summary, the incorporation of green buildings within PEDs not only aligns with the district's energy objectives but also enhances environmental sustainability, energy efficiency, and the overall resilience of the urban environment.

Keywords: positive energy district, renewables energy production, energy flexibility, energy efficiency

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Authors: Jorge Ferro-Diaz, Lazaro Marquez-Llauger, Jose Alberto Camejo-Lamas, Lazaro Marquez-Govea

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The invasion of Scaevola sericea Vahl (Goodeniaceae) in Cuba is a recent process, this exotic invasive species was reported for the first time, in the national territory, by 2008. S. sericea is native to the coasts around the Indian Ocean and western Pacific, common on sandy beaches; it has expanded rapidly around the planet by either natural or anthropic causes, mainly due to its use in hotel gardening. Cuba is highly vulnerable to the colonization of these species, mainly due to tropical hurricanes which have increased in the last decades; it also affects other native species such as Tournefortia gnaphalodes (L.) R. Br. (Boraginaceae) that show invasive manifestations because of the unbalanced state of demographic processes of littoral vegetation, which has been studied by authors during the last 10 years. The fast development of Cuban tourism has encouraged the use of exotic species in gardening that invade large sectors of sandy coasts. Taking into account the importance of assessing the impacts dimensions and adopting effective control measures, a monitoring program for the invasion of S. sericea in Cuba was undertaken. The program has been implemented since 2013 and the main objective was to identify invasive patterns and interactions with other native species of coastal vegetation. This experience also aimed to validate the design and propose a standardized monitoring protocol to be applied throughout the country. In the Cuban territory, 12 sites were chosen, where there were established 24 permanent plots of 100 m2; measurements were taken twice a year taking into consideration variables such as abundance, plant height, soil cover, flora and companion vegetation, density and frequency; other physical variables of the beaches were also measured. Similarly, for associated individuals of T. gnaphalodes, the same variables were measured. The results of these first four years allowed us to document patterns of S. sericea invasion, highlighting the use of adventitious roots to enhance their colonization, and to characterize demographic indicators, ecosystem affections, and interactions with native plants. A density-dependent relationship with T. gnaphalodes was documented, finding a controlling effect on S. sericea, so that a manipulation experiment was applied to evaluate possible management actions to be incorporated in the Plans of the protected areas involved. With these results, it was concluded, for the evaluated sites, that S. sericea has had an invasion dynamics ruled by effects of coastal dynamics, more intense in beaches with affectations to the native vegetation, and more controlled in beaches with more preserved vegetation. It was found that when S. sericea is established, the mechanism that most reinforces its invasion is the use of adventitious roots, used to expand the patches and colonize beach sectors. It was also found that when the density of T. gnaphalodes increases, it detains the expansion of S. sericea and reduces its colonization possibilities, behaving as a natural controller of its biological invasion. The results include a proposal of a new Monitoring Protocol for Scaevola sericea in Cuba, with the possibility of extending its implementation to other countries in the region.

Keywords: biological invasion, exotic invasive species, plant interactions, Scaevola sericea

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Authors: Henry Okechukwu Onyeiwu

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In today’s Nigerian digital age, the landscape of public diplomacy has been significantly altered by the rise of social media platforms like YouTube, Facebook, Twitter, and Instagram. In recent years, social media platforms have emerged as powerful tools for public diplomacy, transforming how countries communicate with both domestic and global audiences. International broadcasting as a tool of public diplomacy has undergone a significant transformation. Traditional methods of state-run media and controlled broadcasting have evolved to incorporate the dynamic, interactive, and decentralized nature of digital platforms. Understanding how Nigerian governments engages in international broadcasting of public diplomacy, the influence of social media on broadcasting public diplomacy, focusing on the advantages and disadvantages of controlling media outlets for diplomatic purposes and also covers the changing nature of global communication in this digital era. As countries navigate the complexities of international relations, the effectiveness of controlled media in shaping public perception and engagement raises significant questions worth exploring. The vast amount of content available can make it challenging to capture and retain audience attention. The ease of spreading false information on social media requires international broadcasters to maintain credibility and counteract misleading narratives. Addressing these challenges requires a comprehensive research that integrates digital communication tools, cultural sensitivity, cybersecurity measures and ongoing evaluation to enhance Nigeria’s international broadcasting of public diplomacy. This study employed a mixed-methods approach, combining qualitative and quantitative research methods. A content analysis of Nigeria’s international broadcasting content was conducted to assess its themes, narratives, and engagement strategies. Additionally, surveys and interviews with communications professionals, diplomats, and social media users were carried out to gather insights on perceptions and effectiveness of public diplomacy initiatives. It has highlighted some of the present trends in technology and the international environmental in which public diplomacy must work, and show how the past can illuminate the road for those navigating this new world. The rise of the social network creates more opportunities than it closes for public diplomacy. This evolution highlights the increasing importance of engagement, mutual understanding, and cooperation in international relations. By Adopting a more inclusive and participatory approach, public diplomacy can more effectively address global challenges and build stronger, more resilient relationships between nations. As Nigeria navigates the complexities of its international relations, this abstract will provide a vital examination of how it can better utilize the dual platforms of international broadcasting and social media in its public diplomacy efforts. The outcome will bear significance not only for Nigeria but also for other nations grappling with similar challenges in the digital age. As social media continues to play a crucial role in public diplomacy, understanding the dynamics of controlled media outlets becomes ever more critical. This abstract shed light on the advantages and disadvantages of such control, ultimately contributing valuable insights to practitioners in the field of diplomacy as they adapt to the rapidly changing communication landscape.

Keywords: international broadcasting, public diplomacy, social media, international relation, polities

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Authors: Tomasz Balabanski, Anna Biedunkiewicz

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Research on basic bacteriological and physicochemical parameters conducted by state institutions (Provincial Sanitary and Epidemiological Station and District Sanitary and Epidemiological Station) are limited to bathing waters under constant sanitary and epidemiological supervision. Unfortunately, no routine or monitoring tests are carried out for the presence of microfungi. This also applies to beach sand used for recreational purposes. The purpose of the planned own research was to determine the diversity of the mycobiota present on supervised and unsupervised sandy beaches, on the shores of lakes, of municipal baths used for recreation. The research material consisted of microfungi isolated from April to October 2019 from sandy beaches of supervised and unsupervised lakes located within the administrative boundaries of the city of Olsztyn (North-Eastern Poland, Europe). Four lakes, out of the fifteen available (Tyrsko, Kortowskie, Skanda, and Ukiel), whose bathing waters are subjected to routine bacteriological tests, were selected for testing. To compare the diversity of the mycobiota composition on the surface and below the sand mixing layer, samples were taken from two depths (10 cm and 50 cm), using a soil auger. Micro-fungi from sand samples were obtained by surface inoculation on an RBC medium from the 1st dilution (1:10). After incubation at 25°C for 96-144 h, the average number of CFU/dm³ was counted. Morphologically differing yeast colonies were passaged into Sabouraud agar slants with gentamicin and incubated again. For detailed laboratory analyses, culture methods (macro- and micro-cultures) and identification methods recommended in diagnostic mycological laboratories were used. The conducted research allowed obtaining 140 yeast isolates. The total average population ranged from 1.37 × 10⁻² CFU/dm³ before the bathing season (April 2019), 1.64 × 10⁻³ CFU/dm³ in the season (May-September 2019), and 1.60 × 10⁻² CFU/dm³ after the end of the season (October 2019). More microfungi were obtained from the surface layer of sand (100 isolates) than from the deeper layer (40 isolates). Reported microfungi may circulate seasonally between individual elements of the lake ecosystem. From the sand/soil from the catchment area beaches, they can get into bathing waters, stopping periodically on the coastal phyllosphere. The sand of the beaches and the phyllosphere are a kind of filter for the water reservoir. The presence of microfungi with various pathogenicity potential in these places is of major epidemiological importance. Therefore, full monitoring of not only recreational waters but also sandy beaches should be treated as an element of constant control by appropriate supervisory institutions, allowing recreational areas for public use so that the use of these places does not involve the risk of infection. Acknowledgment: 'Development Program of the University of Warmia and Mazury in Olsztyn', POWR.03.05.00-00-Z310/17, co-financed by the European Union under the European Social Fund from the Operational Program Knowledge Education Development. Tomasz Bałabański is a recipient of a scholarship from the Programme Interdisciplinary Doctoral Studies in Biology and Biotechnology (POWR.03.05.00-00-Z310/17), which is funded by the 'European Social Fund'.

Keywords: beach, microfungi, sand, yeasts

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Authors: Freya Harding, Anne Gatuguta, Chi Eziefula

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Introduction Research shows the quality of experiences of pregnancy, birth, and postpartum impacts the health and well-being of the mother and baby. This is recognised by the WHO in their recommendations ‘Intrapartum care for a positive childbirth experience’. The COVID-19 pandemic saw the transformation of the NHS Maternity services to prevent the transmission of COVID-19. Physical and social isolation may have affected women’s experiences of pregnancy, birth and postpartum; especially those of healthcare. Examples of such changes made to the NHS include both the reduction in volume of face-to-face consultations and restrictions to visitor time in hospitals. One notable detriment due to these changes was the absence of a partner during certain stages of birth. The aim of this study was to explore women’s experiences of pregnancy, birth, and postnatal period during the COVID-19 pandemic in the UK. Methods We collected qualitative data from women who had given birth during the COVID-19 pandemic. In-depth, semi-structured interviews were conducted with twelve participants recruited from mother and baby groups in Southeast England. Data were audio-recorded, transcribed verbatim, and analysed thematically using both inductive and deductive approaches. Ethics permission was granted from Brighton and Sussex Medical School (ER/BSMS9A83/1). Results Interviews were conducted with 12 women who gave birth between May 2020 and February 2021. Ages of the participants ranged between 28 and 42 years, most of which were white British, with one being Asian British. All participants were heterosexual and either married or co-habiting with their partner. Five participants worked in the NHS, and all participants had professional occupations. Women felt inadequately supported both socially and medically. An appropriate sense of control over their own birthing experience was lacking. Safety mechanisms, such as in-person visits from the midwife, had no suitable alternatives in place. Serious health issues were able to “slip through the net.” Mental health conditions in some of those interviewed worsened or developed. Similarly, reduced support from partners during birth and during the immediate postpartum period at the hospital, coupled with reduced ward staffing, resulted in some traumatic experiences; particularly for women who had undergone caesarean section. However, some unexpected positive effects were reported; one example being that partners were able to spend more time with their baby due to furlough schemes and working from home. Similarly, emergency care was not felt to have been compromised. Overall, six themes emerged: (1) Self-reported traumatic experiences, (2) Challenges of caring for a baby with reduced medical and social support, (3) Unexpected benefits to the parenting experience, (4) The effects of a sudden change in medical management (5) Poor communication from healthcare professionals (6) Social change; with subthemes of support accessing medical care, the workplace, family and friends, and antenatal & baby groups. Conclusions The results indicate that the healthcare system was unable to adequately deliver maternity care to facilitate positive pregnancy, birth, and postnatal experiences during the heights of the pandemic. The poor quality of such experiences has been linked an increased risk of long-term health complications in both the mother and child.

Keywords: pregnancy, birth, postpartum, postnatal, COVID-19, maternity, social support, qualitative, pandemic

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Authors: Anas Hallak, Latifa Seblini, Juergen Wilde

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In mechatronics or sensor technology, plastic housings are used to protect sensitive components from harmful environmental influences, such as moisture, media, or reactive substances. Connections, preferably in the form of metallic lead-frame structures, through the housing wall are required for their electrical supply or control. In this system, an insufficient connection between the plastic component, e.g., Polyamide66, and the metal surface, e.g., copper, due to the incompatibility is dominating. As a result, leakage paths can occur along with the plastic-metal interface. Since adhesive bonding has been established as one of the most important joining processes and its use has expanded significantly, driven by the development of improved high-performance adhesives and bonding techniques, this technology has been involved in metal-plastic hybrid structures. In this study, an epoxy bonding agent from DELO (DUALBOND LT2266) has been used to improve the mechanical and chemical binding between the metal and the polymer. It is an adhesion promoter with two reaction stages. In these, the first stage provides fixation to the lead frame directly after the coating step, which can be done by UV-Exposure for a few seconds. In the second stage, the material will be thermally hardened during injection molding. To analyze the two reaction stages of the primer, dynamic DSC experiments were carried out and correlated with Fourier-transform infrared spectroscopy measurements. Furthermore, the number of crosslinking bonds formed in the system in each reaction stage has also been estimated by a rheological characterization. Those investigations have been performed with different times of UV exposure: 12, 96 s and in an industrial preferred temperature range from -20 to 175°C. The shear viscosity values of primer have been measured as a function of temperature and exposure times. For further interpretation, the storage modulus values have been calculated, and the so-called Booij–Palmen plot has been sketched. The next approach in this study is the self-healing mechanisms in the hydride system in which the primer should flow into micro-damage such as interface, cracks, inhibit them from growing, and close them. The ability of the primer to flow in and penetrate defined capillaries made in Ultramid was investigated. Holes with a diameter of 0.3 mm were produced in injection-molded A3EG7 plates with 4 mm thickness. A copper substrate coated with the DUALBOND was placed on the A3EG7 plate and pressed with a certain force. Metallographic analyses were carried out to verify the filling grade, which showed an almost 95% filling ratio of the capillaries. Finally, to estimate the self-healing mechanism in metal-plastic hybrid systems, characterizations have been done on a simple geometry with a metal inlay developed by the Institute of Polymer Technology in Friedrich-Alexander-University. The specimens have been modified with tungsten wire which was to be pulled out after the injection molding to create a micro-hole in the specimen at the interface between the primer and the polymer. The capability of the primer to heal those micro-cracks upon heating, pressing, and thermal aging has been characterized through metallographic analyses.

Keywords: hybrid structures, self-healing, thermoplastic housing, adhesive

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Authors: Prince S. Campbell, Janine B. Adams, Melusi Thwala, Opeoluwa Oyedele, Paula E. Melariri

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Schistosomiasis is an infectious water-borne disease that holds substantial medical and veterinary importance and is transmitted by Schistosoma flatworms. The transmission and spread of the disease are geographically and temporally confined to water bodies (rivers, lakes, lagoons, dams, etc.) inhabited by its obligate intermediate host snails and human water contact. Human infection with the parasite occurs via skin penetration subsequent to exposure to water infested with schistosome cercariae. Environmental factors play a crucial role in the spread of the disease, as the survival of intermediate host snails is dependent on favourable conditions. These factors include physical and chemical components of water, including pH, salinity, temperature, electrical conductivity, dissolved oxygen, turbidity, water hardness, total dissolved solids, and velocity, as well as biological factors such as predator-prey interactions, competition, food availability, and the presence and density of aquatic vegetation. This study evaluated the physicochemical properties of the water bodies, vegetation type, distribution, and habitat presence of the snail intermediate host. A quantitative cross-sectional research design approach was employed in this study. Eight sampling sites were selected based on their proximity to residential areas. Snails and water physicochemical properties were collected over different seasons for 9 months. A simple dip method was used for surface water samples and measurements were done using multiparameter meters. Snails captured using a 300 µm mesh scoop net and predominant plant species were gathered and transported to experts for identification. Vegetation composition and cover were visually estimated and recorded at each sampling point. Data was analysed using R software (version 4.3.1). A total of 844 freshwater snails were collected, with Physa genera accounting for 95.9% of the snails. Bulinus and Biomphalaria snails, which serve as intermediate hosts for the disease, accounted for (0.9%) and (0.6%) respectively. Indicator macrophytes such as Eicchornia crassipes, Stuckenia pectinate, Typha capensis, and floating macroalgae were found in several water bodies. A negative and weak correlation existed between the number of snails and physicochemical properties such as electrical conductivity (r=-0.240), dissolved oxygen (r=-0.185), hardness (r=-0.210), pH (r=-0.235), salinity (r=-0.242), temperature (r=-0.273), and total dissolved solids (r=-0.236). There was no correlation between the number of snails and turbidity (r=-0.070). Moreover, there was a negative and weak correlation between snails and vegetation coverage (r=-0.127). Findings indicated that snail abundance marginally declined with rising physicochemical concentrations, and the majority of snails were located in regions with less vegetation cover. The reduction in Bulinus and Biomphalaria snail populations may also be attributed to other factors, such as competition among the snails. Snails of the Physa genus were abundant due to their noteworthy resilience in difficult environments. These snails have the potential to function as biological control agents in areas where the disease is endemic, as they outcompete other snails, including schistosomiasis intermediate host snails.

Keywords: intermediate host snails, physicochemical properties, schistosomiasis, vegetation type

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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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Authors: Fabio Rodriguez Sanchez, Josef Bruers, Iciar Arteagoitia, Carlos Rodriguez Andres

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Background: Oral implants are a routine treatment to replace lost teeth. Although they have a high rate of success, implant failures do occur. Perioperative antibiotics have been suggested to prevent postoperative infections and dental implant failures, but they remain a controversial treatment among healthy patients. The objective of this study was to determine whether antibiotic prophylaxis is a common treatment in the Netherlands among general dentists, maxillofacial-surgeons, periodontists and implantologists in conjunction with oral implant surgery among healthy patients and to assess the nature of antibiotics prescriptions in order to evaluate whether any consensus has been reached and the current recommendations are being followed. Methodology: Observational cross-sectional study based on a web-survey reported according to the Strengthening the Reporting of Observational studies in Epidemiology (STROBE) guidelines. A validated questionnaire, developed by Deeb et al. (2015), was translated and slightly adjusted to circumstances in the Netherlands. It was used with the explicit permission of the authors. This questionnaire contained both close-ended and some open-ended questions in relation to the following topics: demographics, qualification, antibiotic type, prescription-duration and dosage. An email was sent February 2018 to a sample of 600 general dentists and all 302 oral implantologists, periodontists and maxillofacial surgeons who were recognized by the Dutch Association of Oral Implantology (NVOI) as oral health care providers placing oral implants. The email included a brief introduction about the study objectives and a link to the web questionnaire, which could be filled in anonymously. Overall, 902 questionnaires were sent. However, 29 questionnaires were not correctly received due to an incorrect email address. So a total number of 873 professionals were reached. Collected data were analyzed using SPSS (IBM Corp., released 2012, Armonk, NY). Results: The questionnaire was sent back by a total number of 218 participants (response rate=24.2%), 45 female (20.8%) and 171 male (79.2%). Two respondents were excluded from the study group because they were not currently working as oral health providers. Overall 151 (69.9%) placed oral implants on regular basis. Approximately 79 (52.7%) of these participants prescribed antibiotics only in determined situations, 66 (44.0%) prescribed antibiotics always and 5 dentists (3.3%) did not prescribe antibiotics at all when placing oral implants. Overall, 83 participants who prescribed antibiotics, did so both pre- and postoperatively (58.5%), 12 exclusively postoperative (8.5%), and 47 followed an exclusive preoperative regime (33.1%). A single dose of 2,000 mg amoxicillin orally 1-hour prior treatment was the most prescribed preoperative regimen. The most frequent prescribed postoperative regimen was 500 mg amoxicillin three times daily for 7 days after surgery. On average, oral health professionals prescribed 6,923 mg antibiotics in conjunction with oral implant surgery, varying from 500 to 14,600 mg. Conclusions: Antibiotic prophylaxis in conjunction with oral implant surgery is prescribed in the Netherlands on a rather large scale. Dutch professionals might prescribe antibiotics more cautiously than in other countries and there seems to be a lower range on the different antibiotic types and regimens being prescribed. Anyway, recommendations based on last-published evidence are frequently not being followed.

Keywords: clinical decision making, infection control, antibiotic prophylaxis, dental implants

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Authors: Hayden R Schott, John M Felder III

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Introduction: Chronic lower extremity wounds in the diabetic and vasculopathic populations are associated with a high degree of morbidity.When wounds require more extensive treatment than can be offered by wound care centers, more aggressive solutions involve local tissue transfer and microsurgical free tissue transfer for achieving definitive soft tissue coverage. These procedures of autologous tissue transfer (ATT) offer resilient, soft tissue coverage of limb-threatening wounds and confer promising limb salvage rates. However, chronic osteomyelitis and recalcitrant soft tissue infections are common in severe diabetic foot wounds and serve to significantly complicate ATT procedures. Stimulan is a resorbable calcium sulfate antibiotic carrier. The use of stimulan antibiotic beads to treat chronic osteomyelitis is well established in the orthopedic and plastic surgery literature. In these procedures, the beads are placed beneath the skin flap to directly deliver antibiotics to the infection site. The purpose of this study was to quantify the success of Stimulan antibiotic beads in treating recalcitrant infections in patients with diabetic foot wounds receiving ATT. Methods: A retrospective review of clinical and demographic information was performed on patients who underwent ATT with the placement of Stimulan antibiotic beads for attempted limb salvage from 2018-21. Patients were analyzed for preoperative wound characteristics, demographics, infection recurrence, and adverse outcomes as a result of product use. The primary endpoint was 90 day infection recurrence, with secondary endpoints including 90 day complications. Outcomes were compared using basic statistics and Fisher’s exact tests. Results: In this time span, 14 patients were identified. At the time of surgery, all patients exhibited clinical signs of active infection, including positive cultures and erythema. 57% of patients (n=8) exhibited chronic osteomyelitis prior to surgery, and 71% (n=10) had exposed bone at the wound base. In 57% of patients (n=8), Stimulan beads were placed beneath a free tissue flap and beneath a pedicle tissue flap in 42% of patients (n=6). In all patients, Stimulan beads were only applied once. Recurrent infections were observed in 28% of patients (n=4) at 90 days post-op, and flap nonadherence was observed in 7% (n=1). These were the only Stimulan related complications observed. Ultimately, lower limb salvage was successful in 85% of patients (n=12). Notably, there was no significant association between the preoperative presence of osteomyelitis and recurrent infections. Conclusions: The use of Stimulanantiobiotic beads to treat recalcitrant infections in patients receiving definitive skin coverage of diabetic foot wounds does not appear to demonstrate unnecessary risk. Furthermore, the lack of significance between the preoperative presence of osteomyelitis and recurrent infections indicates the successful use of Stimulan to dampen infection in patients with osteomyelitis, as is consistent with the literature. Further research is needed to identify Stimulan as the significant contributor to infection treatment using future cohort and case control studies with more patients. Nonetheless, the use of Stimulan antibiotic beads in patients with diabetic foot wounds demonstrates successful infection suppression and maintenance of definitive soft tissue coverage.

Keywords: wound care, stimulan antibiotic beads, free tissue transfer, plastic surgery, wound, infection

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Authors: Juliane Toce, Steven Holochwost

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A substantial and growing literature has demonstrated that arts education benefits young children’s socioemotional and cognitive development. Less is known about the capacity of arts-integrated instruction to yield benefits to similar domains, particularly among demographically and socioeconomically diverse groups of young children. However, the small literature on this topic suggests that arts-integrated instruction may foster young children’s socioemotional and cognitive development by presenting opportunities to 1) engage in instructional content in diverse ways, 2) experience and regulate strong emotions, 3) experience growth-oriented feedback, and 4) engage in collaborative work with peers. Start with the Art is a new program of arts-integrated instruction currently being implemented in four schools in a school district that serves students from a diverse range of backgrounds. The program employs a co-teaching model in which teaching artists and classroom teachers engage in collaborative lesson planning and instruction over the course of the academic year and is currently the focus of an impact study featuring a randomized-control design, as well as an implementation study, both of which are funded through an Educational Innovation and Research grant from the United States Department of Education. The paper will present the early results from the Start with the Art implementation study. These results will provide an overview of the extent to which the program was implemented in accordance with design, with a particular emphasis on the degree to which the four opportunities enumerated above (e.g., opportunities to engage in instructional content in diverse ways) were presented to students. There will be a review key factors that may influence the fidelity of implementation, including classroom teachers’ reception of the program and the extent to which extant conditions in the classroom (e.g., the overall level of classroom organization) may have impacted implementation fidelity. With the explicit purpose of creating a program that values and meets the needs of the teachers and students, Start with the Art incorporates the feedback from individuals participating in the intervention. Tracing its trajectory from inception to ongoing development and examining the adaptive changes made in response to teachers' transformative experiences in the post-pandemic classroom, Start with the Art continues to solicit input from experts in integrating artistic content into core curricula within educational settings catering to students from under-represented backgrounds in the arts. Leveraging the input from this rich consortium of experts has allowed for a comprehensive evaluation of the program’s implementation. The early findings derived from the implementation study emphasize the potential of arts-integrated instruction to incorporate restorative practices. Such practices serve as a crucial support system for both students and educators, providing avenues for children to express themselves, heal emotionally, and foster social development, while empowering teachers to create more empathetic, inclusive, and supportive learning environments. This all-encompassing analysis spotlights Start with the Art’s adaptability to any learning environment through the program’s effectiveness, resilience, and its capacity to transform - through art - the classroom experience within the ever-evolving landscape of education.

Keywords: arts-integration, social emotional learning, diverse learners, co-teaching, teaching artists, post-pandemic teaching

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Authors: Juan Pablo Bertuzzi, Mauro Chiarella

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Employing a communication studies perspective and a socio-technological approach, this paper introduces a theoretical framework for understanding the concept of hybrid world; the avatarization phenomena; and the communicational archetype of co-hybridization. This analysis intends to make a contribution to future design of virtual reality experimental applications. Ultimately, this paper presents an ongoing research project that proposes the study of human-avatar interactions in digital educational environments, as well as an innovative reflection on inner digital communication. The aforementioned project presents the analysis of human-avatar interactions, through the development of an interactive experience in virtual reality. The goal is to generate an innovative communicational dimension that could reinforce the hypotheses presented throughout this paper. Being thought for its initial application in educational environments, the analysis and results of this research are dependent and have been prepared in regard of a meticulous planning of: the conception of a 3D digital platform; the interactive game objects; the AI or computer avatars; the human representation as hybrid avatars; and lastly, the potential of immersion, ergonomics and control diversity that can provide the virtual reality system and the game engine that were chosen. The project is divided in two main axes: The first part is the structural one, as it is mandatory for the construction of an original prototype. The 3D model is inspired by the physical space that belongs to an academic institution. The incorporation of smart objects, avatars, game mechanics, game objects, and a dialogue system will be part of the prototype. These elements have all the objective of gamifying the educational environment. To generate a continuous participation and a large amount of interactions, the digital world will be navigable both, in a conventional device and in a virtual reality system. This decision is made, practically, to facilitate the communication between students and teachers; and strategically, because it will help to a faster population of the digital environment. The second part is concentrated to content production and further data analysis. The challenge is to offer a scenario’s diversity that compels users to interact and to question their digital embodiment. The multipath narrative content that is being applied is focused on the subjects covered in this paper. Furthermore, the experience with virtual reality devices proposes users to experiment in a mixture of a seemingly infinite digital world and a small physical area of movement. This combination will lead the narrative content and it will be crucial in order to restrict user’s interactions. The main point is to stimulate and to grow in the user the need of his hybrid avatar’s help. By building an inner communication between user’s physicality and user’s digital extension, the interactions will serve as a self-guide through the gameworld. This is the first attempt to make explicit the avatarization phenomena and to further analyze the communicational archetype of co-hybridization. The challenge of the upcoming years will be to take advantage from these forms of generalized avatarization, in order to create awareness and establish innovative forms of hybridization.

Keywords: avatar, hybrid worlds, socio-technology, virtual reality

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Authors: Esna B. Buğday, Niray Tunçel

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Spirituality has a motivational influence on consumers' psychological states, lifestyles, and behavioral intentions. Spirituality refers to the feeling that there is a divine power greater than ourselves and a connection among oneself, others, nature, and the sacred. In addition, spirituality concerns the human soul and spirit against the material and physical world and consists of three dimensions: self-discovery, relationships, and belief in a higher power. Of them, self-discovery is to explore the meaning and the purpose of life. Relationships refer to the awareness of the connection between human beings and nature as well as respect for them. In addition, higher power represents the transcendent aspect of spirituality, which means to believe in a holy power that creates all the systems in the universe. Furthermore, a voluntary simplicity lifestyle is (1) to adopt a simple lifestyle by minimizing the attachment to and the consumption of material things and possessions, (2) to have an ecological awareness respecting all living creatures, and (3) to express the desire for exploring and developing the inner life. Voluntary simplicity is a multi-dimensional construct that consists of a desire for a voluntarily simple life (e.g., avoiding excessive consumption), cautious attitudes in shopping (e.g., not buying unnecessary products), acceptance of self-sufficiency (e.g., being self-sufficient individual), and rejection of highly developed functions of products (e.g., preference for simple functioned products). One of the main reasons for living simply is to sustain a spiritual life, as voluntary simplicity provides the space for achieving psychological and spiritual growth, cultivating self-reliance since voluntary simplifier frees themselves from the overwhelming externals and takes control of their daily lives. From this point of view, it is expected that people with a strong sense of spirituality will be likely to adopt a simple lifestyle. In this respect, the study aims to examine the impact of spirituality on consumers' voluntary simple lifestyle tendencies. As consumers' consumption attitudes and behaviors depend on their lifestyles, exploring the factors that lead them to embrace voluntary simplicity significantly predicts their purchase behavior. In this respect, this study presents empirical research based on a data set collected from 478 Turkish consumers through an online survey. First, exploratory factor analysis is applied to the data to reveal the dimensions of spirituality and voluntary simplicity scales. Second, confirmatory factor analysis is conducted to assess the measurement model. Last, the hypotheses are analyzed using partial least square structural equation modeling (PLS-SEM). The results confirm that spirituality's self-discovery and relationships dimensions positively impact both cautious attitudes in shopping and acceptance of self-sufficiency dimensions of voluntary simplicity. In contrast, belief in a higher power does not significantly influence consumers' voluntary simplicity tendencies. Even though there has been theoretical support drawing a positive relationship between spirituality and voluntary simplicity, to the best of the authors' knowledge, this has not been empirically tested in the literature before. Hence, this study contributes to the current knowledge by analyzing the direct influence of spirituality on consumers' voluntary simplicity tendencies. Additionally, analyzing this impact on the consumers of an emerging market is another contribution to the literature.

Keywords: spirituality, voluntary simplicity, self-sufficiency, conscious shopping, Turkish consumers

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Authors: Ksenia Volkova, Artur Petrosyan, Ignatii Dubyshkin, Alexei Ossadtchi

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Brain-computer interfaces are a growing research field producing many implementations that find use in different fields and are used for research and practical purposes. Despite the popularity of the implementations using non-invasive neuroimaging methods, radical improvement of the state channel bandwidth and, thus, decoding accuracy is only possible by using invasive techniques. Electrocorticography (ECoG) is a minimally invasive neuroimaging method that provides highly informative brain activity signals, effective analysis of which requires the use of machine learning methods that are able to learn representations of complex patterns. Deep learning is a family of machine learning algorithms that allow learning representations of data with multiple levels of abstraction. This study explores the potential of deep learning approaches for ECoG processing, decoding movement intentions and the perception of proprioceptive information. To obtain synchronous recording of kinematic movement characteristics and corresponding electrical brain activity, a series of experiments were carried out, during which subjects performed finger movements at their own pace. Finger movements were recorded with a three-axis accelerometer, while ECoG was synchronously registered from the electrode strips that were implanted over the contralateral sensorimotor cortex. Then, multichannel ECoG signals were used to track finger movement trajectory characterized by accelerometer signal. This process was carried out both causally and non-causally, using different position of the ECoG data segment with respect to the accelerometer data stream. The recorded data was split into training and testing sets, containing continuous non-overlapping fragments of the multichannel ECoG. A deep convolutional neural network was implemented and trained, using 1-second segments of ECoG data from the training dataset as input. To assess the decoding accuracy, correlation coefficient r between the output of the model and the accelerometer readings was computed. After optimization of hyperparameters and training, the deep learning model allowed reasonably accurate causal decoding of finger movement with correlation coefficient r = 0.8. In contrast, the classical Wiener-filter like approach was able to achieve only 0.56 in the causal decoding mode. In the noncausal case, the traditional approach reached the accuracy of r = 0.69, which may be due to the presence of additional proprioceptive information. This result demonstrates that the deep neural network was able to effectively find a representation of the complex top-down information related to the actual movement rather than proprioception. The sensitivity analysis shows physiologically plausible pictures of the extent to which individual features (channel, wavelet subband) are utilized during the decoding procedure. In conclusion, the results of this study have demonstrated that a combination of a minimally invasive neuroimaging technique such as ECoG and advanced machine learning approaches allows decoding motion with high accuracy. Such setup provides means for control of devices with a large number of degrees of freedom as well as exploratory studies of the complex neural processes underlying movement execution.

Keywords: brain-computer interface, deep learning, ECoG, movement decoding, sensorimotor cortex

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Authors: Yi-Hao Wong, Li-Li Chan, Chee-Onn Leong, Stephen Ambu, Joon-Wah Mak, Priyasashi Sahu

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Background: Acanthamoeba is a genus of amoebae which lives as a free-living in nature or as a human pathogen that causes severe brain and eye infections. Virulence potential of Acanthamoeba is not constant and can change with growth conditions. DNA methylation, an epigenetic process which adds methyl groups to DNA, is used by eukaryotic cells, including several human parasites to control their gene expression. We used qPCR, siRNA gene silencing, and RNA sequencing (RNA-Seq) to study DNA-methyltransferase gene family (DNMT) in order to indicate the possibility of its involvement in programming Acanthamoeba virulence potential. Methods: A virulence-attenuated Acanthamoeba isolate (designation: ATCC; original isolate: ATCC 50492) was subjected to mouse passages to restore its pathogenicity; a virulence-reactivated isolate (designation: AC/5) was generated. Several established factors associated with Acanthamoeba virulence phenotype were examined to confirm the succession of reactivation process. Differential gene expression of DNMT between ATCC and AC/5 isolates was performed by qPCR. Silencing on DNMT gene expression in AC/5 isolate was achieved by siRNA duplex. Total RNAs extracted from ATCC, AC/5, and siRNA-treated (designation: si-146) were subjected to RNA-Seq for comparative transcriptomic analysis in order to identify the genome-wide effect of DNMT in regulating Acanthamoeba gene expression. qPCR was performed to validate the RNA-Seq results. Results: Physiological and cytophatic assays demonstrated an increased in virulence potential of AC/5 isolate after mouse passages. DNMT gene expression was significantly higher in AC/5 compared to ATCC isolate (p ≤ 0.01) by qPCR. si-146 duplex reduced DNMT gene expression in AC/5 isolate by 30%. Comparative transcriptome analysis identified the differentially expressed genes, with 3768 genes in AC/5 vs ATCC isolate; 2102 genes in si-146 vs AC/5 isolate and 3422 genes in si-146 vs ATCC isolate, respectively (fold-change of ≥ 2 or ≤ 0.5, p-value adjusted (padj) < 0.05). Of these, 840 and 1262 genes were upregulated and downregulated, respectively, in si-146 vs AC/5 isolate. Eukaryotic orthologous group (KOG) assignments revealed a higher percentage of downregulated gene expression in si-146 compared to AC/5 isolate, were related to posttranslational modification, signal transduction and energy production. Gene Ontology (GO) terms for those downregulated genes shown were associated with transport activity, oxidation-reduction process, and metabolic process. Among these downregulated genes were putative genes encoded for heat shock proteins, transporters, ubiquitin-related proteins, proteins for vesicular trafficking (small GTPases), and oxidoreductases. Functional analysis of similar predicted proteins had been described in other parasitic protozoa for their survival and pathogenicity. Decreased expression of these genes in si146-treated isolate may account in part for Acanthamoeba reduced pathogenicity. qPCR on 6 selected genes upregulated in AC/5 compared to ATCC isolate corroborated the RNA sequencing findings, indicating a good concordance between these two analyses. Conclusion: To the best of our knowledge, this study represents the first genome-wide analysis of DNA methylation and its effects on gene expression in Acanthamoeba spp. The present data indicate that DNA methylation has substantial effect on global gene expression, allowing further dissection of the genome-wide effects of DNA-methyltransferase gene in regulating Acanthamoeba pathogenicity.

Keywords: Acanthamoeba, DNA methylation, RNA sequencing, virulence

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Authors: Ousmane Sarr

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The Senegalese coasts have high productivity of fishery resources due to the frequency of intense up-welling system that occurs along its coast, caused by the maritime trade winds making its waters nutrients rich. Fishing plays a primordial role in Senegal's socioeconomic plans and food security. However, a global diagnosis of the Senegalese maritime fishing sector has highlighted the challenges this sector encounters. Among these concerns, some significant stocks, a priority target for artisanal fishing, need further assessment. If no efforts are made in this direction, most stock will be overexploited or even in decline. It is in this context that this research was initiated. This investigation aimed to apply a multi-modal approach (LBB, Catch-only-based CMSY model and its most recent version (CMSY++); JABBA, and JABBA-Select) to assess the stock of Atlantic bonito, Sarda sarda (Bloch, 1793) in the Senegalese Exclusive Economic Zone (SEEZ). Available catch, effort, and size data from Atlantic bonito over 15 years (2004-2018) were used to calculate the nominal and standardized CPUE, size-frequency distribution, and length at retentions (50 % and 95 % selectivity) of the species. These relevant results were employed as input parameters for stock assessment models mentioned above to define the stock status of this species in this region of the Atlantic Ocean. The LBB model indicated an Atlantic bonito healthy stock status with B/BMSY values ranging from 1.3 to 1.6 and B/B0 values varying from 0.47 to 0.61 of the main scenarios performed (BON_AFG_CL, BON_GN_Length, and BON_PS_Length). The results estimated by LBB are consistent with those obtained by CMSY. The CMSY model results demonstrate that the SEEZ Atlantic bonito stock is in a sound condition in the final year of the main scenarios analyzed (BON, BON-bt, BON-GN-bt, and BON-PS-bt) with sustainable relative stock biomass (B2018/BMSY = 1.13 to 1.3) and fishing pressure levels (F2018/FMSY= 0.52 to 1.43). The B/BMSY and F/FMSY results for the JABBA model ranged between 2.01 to 2.14 and 0.47 to 0.33, respectively. In contrast, The estimated B/BMSY and F/FMSY for JABBA-Select ranged from 1.91 to 1.92 and 0.52 to 0.54. The Kobe plots results of the base case scenarios ranged from 75% to 89% probability in the green area, indicating sustainable fishing pressure and an Atlantic bonito healthy stock size capable of producing high yields close to the MSY. Based on the stock assessment results, this study highlighted scientific advice for temporary management measures. This study suggests an improvement of the selectivity parameters of longlines and purse seines and a temporary prohibition of the use of sleeping nets in the fishery for the Atlantic bonito stock in the SEEZ based on the results of the length-base models. Although these actions are temporary, they can be essential to reduce or avoid intense pressure on the Atlantic bonito stock in the SEEZ. However, it is necessary to establish harvest control rules to provide coherent and solid scientific information that leads to appropriate decision-making for rational and sustainable exploitation of Atlantic bonito in the SEEZ and the Eastern Atlantic Ocean.

Keywords: multi-model approach, stock assessment, atlantic bonito, SEEZ

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Authors: R. Pardo, P. Menendez, MA Gil-Olarte, S. Sanchez, E. García, R. Quintana, J. Martín

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Introduction : Within oncoplastic breast techniques there is increased interest in immediate partial breast reconstruction. The volume resected is greater than that of conventional conservative techniques. Central tumours of the breast have classically been treated with a mastectomy with regard to oncological safety and cosmetic secondary effects after wide central resection of the nipple and breast tissue beneath. Oncological results for central quadrantectomy have a recurrence level, disease- free period and survival identical to mastectomy. Grissoti flap is an oncoplastic surgical technique that allows the surgeon to perform a safe central quadrantectomy with excellent cosmetic results. Material and methods: The Grissoti flap is a glandular cutaneous advancement rotation flap that can fill the defect in the central portion of the excised breast. If the inferior border is affected by tumour and further surgery is decided upon at the Multidisciplinary Team Meeting, it will be necessary to perform a mastectomy. All patients with a Grisotti flap undergoing surgery since 2009 were reviewed obtaining the following data: age, hystopathological diagnosis, size, operating time, volume of tissue resected, postoperative admission time, re-excisions due to positive margins affected by tumour, wound dehiscence, complications and recurrence. Analysis and results of sentinel node biopsy were also obtained. Results: 12 patients underwent surgery between 2009-2015. The mean age was 54 years (34-67) . All had a preoperative diagnosis of ductal infiltrative carcinoma of less than 2 cm,. Diagnosis was made with Ultrasound, Mamography or both . Magnetic resonance was used in 5 cases. No patients had preoperative positive axilla after ultrasound exploration. Mean operating time was 104 minutes (84-130). Postoperative stay was 24 hours. Mean volume resected was 159 cc (70-286). In one patient the surgical border was affected by tumour and a further procedure with resection of the affected border was performed as ambulatory surgery. The sentinel node biopsy was positive for micrometastasis in only two cases. In one case lymphadenectomy was performed in 2009. In the other, treated in 2015, no lymphadenectomy was performed as the patient had a favourable histopathological prognosis and the multidisciplinary team meeting agreed that lymphadenectomy was not required. No recurrence has been diagnosed in any of the patients who underwent surgery and they are all disease free at present. Conclusions: Conservative surgery for retroareolar central tumours of the breast results in good local control of the disease with free surgical borders, including resection of the nipple areola complex and pectoral major muscle fascia. Reconstructive surgery with the inferior Grissoti flap adequately fills the defect after central quadrantectomy with creation of a new cutaneous disc where a new nipple areola complex is reconstructed with a local flap or micropigmentation. This avoids the need for contralateral symmetrization. Sentinel Node biopsy can be performed without added morbidity. When feasible, the Grissoti flap will avoid skin-sparing mastectomy for central breast tumours that will require the use of an expander, prosthesis or myocutaneous flap, with all the complications of a more complex operation.

Keywords: Grisotti flap, oncoplastic surgery, central tumours, breast

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Authors: Dina Farran, Mark Ashworth, Fiona Gaughran

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Atrial fibrillation (AF), the most prevalent cardiac arrhythmia, is associated with an increased risk of stroke, contributing to heart failure and death. In this project, we aim to improve patient safety by screening for stroke risk among people with AF and co-morbid mental illness. To do so, we started by conducting a systematic review and meta-analysis on prevalence, management, and outcomes of AF in people with Serious Mental Illness (SMI) versus the general population. We then evaluated oral anticoagulation (OAC) prescription trends in people with AF and co-morbid SMI in King’s College Hospital. We also evaluated the association between mental illness severity and OAC prescription in eligible patients in South London and Maudsley (SLaM) NHS Foundation Trust. Next, we implemented an electronic clinical decision support system (eCDSS) consisting of a visual prompt on patient electronic Personal Health Records to screen for AF-related stroke risk in three Mental Health of Older Adults wards at SLaM. Finally, we assessed the feasibility and acceptability of the eCDSS by qualitatively investigating clinicians’ perspectives of the potential usefulness of the eCDSS (pre-intervention) and their experiences and their views regarding its impact on clinicians and patients (post-intervention). The systematic review showed that people with SMI had low reported rates of AF. AF patients with SMI were less likely to receive OAC than the general population. When receiving warfarin, people with SMI, particularly bipolar disorder, experienced poor anticoagulation control compared to the general population. Meta-analysis showed that SMI was not significantly associated with an increased risk of stroke or major bleeding when adjusting for underlying risk factors. The main findings of the first observational study were that among AF patients having a high stroke risk, those with co-morbid SMI were less likely than non-SMI to be prescribed any OAC, particularly warfarin. After 2019, there was no significant difference between the two groups. In the second observational study, patients with AF and co-morbid SMI were less likely to be prescribed any OAC compared to those with dementia, substance use disorders, or common mental disorders, adjusting for age, sex, stroke, and bleeding risk scores. Among AF patients with co-morbid SMI, warfarin was less likely to be prescribed to those having alcohol or substance dependency, serious self-injury, hallucinations or delusions, and activities of daily living impairment. In the intervention, clinicians were asked to confirm the presence of AF, clinically assess stroke and bleeding risks, record risk scores in clinical notes, and refer patients at high risk of stroke to OAC clinics. Clinicians reported many potential benefits for the eCDSS, including improving clinical effectiveness, better identification of patients at risk, safer and more comprehensive care, consistency in decision making and saving time. Identified potential risks included rigidity in decision-making, overreliance, reduced critical thinking, false positive recommendations, annoyance, and increased workload. This study presents a unique opportunity to quantify AF patients with mental illness who are at high risk of severe outcomes using electronic health records. This has the potential to improve health outcomes and, therefore patients' quality of life.

Keywords: atrial fibrillation, stroke, mental health conditions, electronic clinical decision support systems

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Authors: Omer Zvi Shaked, Amir Tirosh

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Type 1 Diabetes (T1DM) is an incurable chronic illness with no known preventive measures. Excess to insulin therapy can lead to hypoglycemia with neuro-glycogenic symptoms such as shakiness, nausea, sweating, irritability, fatigue, excessive thirst or hunger, weakness, seizure, and coma. Severe Hypoglycemia (SH) is also considered a most aversive event since it may put patients at risk for injury and death, which matches the criteria of a traumatic event. SH has a ranging prevalence of 20%, which makes it a primary medical Issue. One of the results of SH is an intense emotional fear reaction resembling the form of post-traumatic stress symptoms (PTS), causing many patients to avoid insulin therapy and social activities in order to avoid the possibility of hypoglycemia. As a result, they are at risk for irreversible health deterioration and medical complications. Fear of Hypoglycemia (FOH) is, therefore, a major disturbance for T1DM patients. FOH differs from prevalent post-traumatic stress reactions to other forms of traumatic events since the threat to life continuously exists in the patient's body. That is, it is highly probable that orthodox interventions may not be sufficient for helping patients after SH to regain healthy social function and proper medical treatment. Accordingly, the current presentation will demonstrate the results of a study conducted among T1DM patients after SH. The study was designed in two stages. First, a preliminary qualitative phenomenological study among ten patients after SH was conducted. Analysis revealed that after SH, patients confuse between stress symptoms and Hypoglycemia symptoms, divide life before and after the event, report a constant sense of fear, a loss of freedom, a significant decrease in social functioning, a catastrophic thinking pattern, a dichotomous split between the self and the body, and internalization of illness identity, a loss of internal locus of control, a damaged self-representation, and severe loneliness for never being understood by others. The second stage was a two steps study of intervention among five patients after SH. The first part of the intervention included three months of therapeutic 3rd wave CBT therapy. The contents of the therapeutic process were: acceptance of fear and tolerance to stress; cognitive de-fusion combined with emotional self-regulation; the adoption of an active position relying on personal values; and self-compassion. Then, the intervention included a one-week practical real-time 24/7 support by trained medical personnel, alongside a gradual exposure to increased insulin therapy in a protected environment. The results of the intervention are a decrease in stress symptoms, increased social functioning, increased well-being, and decreased avoidance of medical treatment. The presentation will discuss the unique emotional state of T1DM patients after SH. Then, the presentation will discuss the effectiveness of the intervention for patients with chronic conditions after a traumatic event. The presentation will make evident the unique situation of illness-related PTSD. The presentation will also demonstrate the requirement for multi-professional collaboration between social work and medical care for populations with chronic medical conditions. Limitations of the study and recommendations for further research will be discussed.

Keywords: type 1 diabetes, chronic illness, post-traumatic stress, illness-related PTSD

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Authors: Ning Chia

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Each of the three different language texts (Manchu, Russian, and Latin) of the 1689 Treaty of Nerchinsk bore official seals from Imperial Russia and Qing China. These seals have received no academic attention, yet they can reveal a site of a layered and shared material, cultural, political, and diplomatic world of the time in Eastern Eurasia. The very different seal selections from both empires while ratifying the Treaty of Beijing in 1860 have obtained no scholarly advertency either; they can also explicate a tremendously changed relationship with visual and material manifestation. Exploring primary sources in Manchu, Russian, and Chinese languages as well as the images of the visual seals, this study investigates the reasons and purposes of utilizing official seals for the treaty agreement. A refreshed understanding of Russian-Qing diplomacy will be developed by pursuing the following aspects: (i) Analyzing the iconographic meanings of each seal insignia and unearthing a competitive, yet symbols-delivered and seal-generated, 'dialogue' between the two empires (ii) Contextualizing treaty seals within the historical seal cultures, and discovering how domestic seal system in each empire’s political institution developed into treaty-defined bilateral relations (iii) Expounding the seal confiding in each empire’s daily governing routines, and annotating the trust in the seal as a quested promise from the opponent negotiator to fulfill the treaty terms (iv) Contrasting the two seal traditions along two civilization-lines, Eastern vs. Western, and dissecting how the two styles of seal emblems affected the cross-cultural understanding or misunderstanding between the two empires (v) Comprehending the history-making events from the substantial resources such as the treaty seals, and grasping why the seals for the two treaties, so different in both visual design and symbolic value, were chosen in the two relationship eras (vi) Correlating the materialized seal 'expression' and the imperial worldviews based on each empire’s national/or power identity, and probing the seal-represented 'rule under the Heaven' assumption of China and Russian rising role in 'European-American imperialism … centered on East Asia' (Victor Shmagin, 2020). In conclusion, the impact of official seals on diplomatic treaties needs profound knowledge in seal history, insignia culture, and emblem belief to be able to comprehend. The official seals in both Imperial Russia and Qing China belonged to a particular statecraft art in a specific material and visual form. Once utilized in diplomatic treaties, the meticulously decorated and politically institutionalized seals were transformed from the determinant means for domestic administration and social control into the markers of an empire’s sovereign authority. Overlooked in historical practice, the insignia seal created a wire of 'visual contest' between the two rival powers. Through this material lens, the scholarly knowledge of the Russian-Qing diplomatic relationship will be significantly upgraded. Connecting Russian studies, Qing/Chinese studies, and Eurasian studies, this study also ties material culture, political culture, and diplomatic culture together. It promotes the study of official seals and emblem symbols in worldwide diplomatic history.

Keywords: Russia-Qing diplomatic relation, Treaty of Beijing (1860), Treaty of Nerchinsk (1689), Treaty seals

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Authors: Sagar Saroha, Sawan S. Sinha, Sunil Lakshmipathy

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Reynolds averaged Navier-Stokes (RANS) model is the popular computational tool for prediction of turbulent flows. Being computationally less expensive as compared to direct numerical simulation (DNS), RANS has received wide acceptance in industry and research community as well. However, for high Reynolds number flows, the traditional RANS approach based on the Boussinesq hypothesis is incapacitated to capture all the essential flow characteristics, and thus, its performance is restricted in high Reynolds number flows of practical interest. RANS performance turns out to be inadequate in regimes like flow over curved surfaces, flows with rapid changes in the mean strain rate, duct flows involving secondary streamlines and three-dimensional separated flows. In the recent decade, partially averaged Navier-Stokes (PANS) methodology has gained acceptability among seamless bridging methods of turbulence- placed between DNS and RANS. PANS methodology, being a scale resolving bridging method, is inherently more suitable than RANS for simulating turbulent flows. The superior ability of PANS method has been demonstrated for some cases like swirling flows, high-speed mixing environment, and high Reynolds number turbulent flows. In our work, we intend to evaluate PANS in case of separated turbulent flows past bluff bodies -which is of broad aerodynamic research and industrial application. PANS equations, being derived from base RANS, continue to inherit the inadequacies from the parent RANS model based on linear eddy-viscosity model (LEVM) closure. To enhance PANS’ capabilities for simulating separated flows, the shortcomings of the LEVM closure need to be addressed. Inabilities of the LEVMs have inspired the development of non-linear eddy viscosity models (NLEVM). To explore the potential improvement in PANS performance, in our study we evaluate the PANS behavior in conjugation with NLEVM. Our work can be categorized into three significant steps: (i) Extraction of PANS version of NLEVM from RANS model, (ii) testing the model in the homogeneous turbulence environment and (iii) application and evaluation of the model in the canonical case of separated non-homogeneous flow field (flow past prismatic bodies and bodies of revolution at high Reynolds number). PANS version of NLEVM shall be derived and implemented in OpenFOAM -an open source solver. Homogeneous flows evaluation will comprise the study of the influence of the PANS’ filter-width control parameter on the turbulent stresses; the homogeneous analysis performed over typical velocity fields and asymptotic analysis of Reynolds stress tensor. Non-homogeneous flow case will include the study of mean integrated quantities and various instantaneous flow field features including wake structures. Performance of PANS + NLEVM shall be compared against the LEVM based PANS and LEVM based RANS. This assessment will contribute to significant improvement of the predictive ability of the computational fluid dynamics (CFD) tools in massively separated turbulent flows past bluff bodies.

Keywords: bridging methods of turbulence, high Re-CFD, non-linear PANS, separated turbulent flows

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Authors: Prince Chukwuneme Enwereji, Annelien Van Rooyen

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In recent years, technology integration in education has transformed the learning landscape, particularly in online institutions. One technological advancement that has gained popularity is e-tutoring, which offers personalised academic support to students through online platforms. While e-tutoring has become well-known and has been adopted to promote collaborative learning, there are still students who do not use these services for various reasons. However, little attention has been given to understanding the perspectives of students who have not utilized these services. The research objectives include identifying the perceived benefits that non-e-tutoring students believe e-tutoring could offer, such as enhanced academic support, personalized learning experiences, and improved performance. Additionally, the study explored the potential drawbacks or concerns that non-e-tutoring students associate with e-tutoring, such as concerns about efficacy, a lack of face-to-face interaction, and platform accessibility. The study adopted a quantitative research approach with a descriptive design to gather and analyze data on non-e-tutoring students' perspectives. Online questionnaires were employed as the primary data collection method, allowing for the efficient collection of data from many participants. The collected data was analyzed using the Statistical Package for the Social Sciences (SPSS). Ethical concepts such as informed consent, anonymity of responses and protection of respondents against harm were maintained. Findings indicate that non-e-tutoring students perceive a sense of control over their own pace of learning, suggesting a preference for self-directed learning and the ability to tailor their educational experience to their individual needs and learning styles. They also exhibit high levels of motivation, believe in their ability to effectively participate in their studies and organize their academic work, and feel comfortable studying on their own without the help of e-tutors. However, non-e-tutoring students feel that e-tutors do not sufficiently address their academic needs and lack engagement. They also perceive a lack of clarity in the roles of e-tutors, leading to uncertainty about their responsibilities. In terms of communication, students feel overwhelmed by the volume of announcements and find repetitive information frustrating. Additionally, some students face challenges with their internet connection and associated cost, which can hinder their participation in online activities. Furthermore, non-e-tutoring students express a desire for interactions with their peers and a sense of belonging to a group or team. They value opportunities for collaboration, teamwork in their learning experience, the importance of fostering social interactions and creating a sense of community in online learning environments. This study recommended that students seek alternate support systems by reaching out to professors or academic advisors for guidance and clarification. Developing self-directed learning skills is essential, empowering students to take charge of their own learning through setting objectives, creating own study plans, and utilising resources. For HEIs, it was recommended that they should ensure that a variety of support services are available to cater to the needs of all students, including non-e-tutoring students. HEIs should also ensure easy access to online resources, promote a supportive community, and regularly evaluate and adapt their support techniques to meet students' changing requirements.

Keywords: online-tutor;, student support;, online education, educational practices, distance education

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Authors: Tatiana Butkova, Nikolai Kibrik, Kristina Malsagova, Alexander Izotov, Alexander Stepanov, Anna Kaysheva

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Relevance. The genetic risk of developing schizophrenia is determined by two factors: single nucleotide polymorphisms and gene copy number variations. The search for serological markers for early diagnosis of schizophrenia is driven by the fact that the first five years of the disease are accompanied by significant biological, psychological, and social changes. It is during this period that pathological processes are most amenable to correction. The aim of this study was to analyze single nucleotide polymorphisms (SNPs) that are hypothesized to potentially influence the onset and development of the endogenous process. Materials and Methods It was analyzed 73 single nucleotide polymorphism variants. The study included 48 patients undergoing inpatient treatment at "Psychiatric Clinical Hospital No. 1" in Moscow, comprising 23 females and 25 males. Inclusion criteria: - Patients aged 18 and above. - Diagnosis according to ICD-10: F20.0, F20.2, F20.8, F21.8, F25.1, F25.2. - Voluntary informed consent from patients. Exclusion criteria included: - The presence of concurrent somatic or neurological pathology, neuroinfections, epilepsy, organic central nervous system damage of any etiology, and regular use of medication. - Substance abuse and alcohol dependence. - Women who were pregnant or breastfeeding. Clinical and psychopathological assessment was complemented by psychometric evaluation using the PANSS scale at the beginning and end of treatment. The duration of observation during therapy was 4-6 weeks. Total DNA extraction was performed using QIAamp DNA. Blood samples were processed on Illumina HiScan and genotyped for 652,297 markers on the Infinium Global Chips Screening Array-24v2.0 using the IMPUTE2 program with parameters Ne=20,000 and k=90. Additional filtration was performed based on INFO>0.5 and genotype probability>0.5. Quality control of the obtained DNA was conducted using agarose gel electrophoresis, with each tested sample having a volume of 100 µL. Results. It was observed that several SNPs exhibited gender dependence. We identified groups of single nucleotide polymorphisms with a membership of 80% or more in either the female or male gender. These SNPs included rs2661319, rs2842030, rs4606, rs11868035, rs518147, rs5993883, and rs6269.Another noteworthy finding was the limited combination of SNPs sufficient to manifest clinical symptoms leading to hospitalization. Among all 48 patients, each of whom was analyzed for deviations in 73 SNPs, it was discovered that the combination of involved SNPs in the manifestation of pronounced clinical symptoms of schizophrenia was 19±3 out of 73 possible. In study, the frequency of occurrence of single nucleotide polymorphisms also varied. The most frequently observed SNPs were rs4849127 (in 90% of cases), rs1150226 (86%), rs1414334 (75%), rs10170310 (73%), rs2857657, and rs4436578 (71%). Conclusion. Thus, the results of this study provide additional evidence that these genes may be associated with the development of schizophrenia spectrum disorders. However, it's impossible cannot rule out the hypothesis that these polymorphisms may be in linkage disequilibrium with other functionally significant polymorphisms that may actually be involved in schizophrenia spectrum disorders. It has been shown that missense SNPs by themselves are likely not causative of the disease but are in strong linkage disequilibrium with non-functional SNPs that may indeed contribute to disease predisposition.

Keywords: gene polymorphisms, genotyping, single nucleotide polymorphisms, schizophrenia.

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Authors: Loyd R. Hook, Maryam Moharek

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With the envisioned future growth of low altitude urban aircraft operations for airborne delivery service and advanced air mobility, strategies to coordinate and deconflict aircraft flight paths must be prioritized. Autonomous coordination and planning of flight trajectories is the preferred approach to the future vision in order to increase safety, density, and efficiency over manual methods employed today. Difficulties arise because any conflict resolution must be constrained by all other aircraft, all airspace restrictions, and all ground-based obstacles in the vicinity. These considerations make pair-wise tactical deconfliction difficult at best and unlikely to find a suitable solution for the entire system of vehicles. In addition, more traditional methods which rely on long time scales and large protected zones will artificially limit vehicle density and drastically decrease efficiency. Instead, strategic planning, which is able to respond to highly dynamic conditions and still account for high density operations, will be required to coordinate multiple vehicles in the highly constrained low altitude urban environment. This paper develops and evaluates such a planning algorithm which can be implemented autonomously across multiple aircraft and situations. Data from this evaluation provide promising results with simulations showing up to 10 aircraft deconflicted through a relatively narrow low-altitude urban canyon without any vehicle to vehicle or obstacle conflict. The algorithm achieves this level of coordination beginning with the assumption that each vehicle is controlled to follow an independently constructed flight path, which is itself free of obstacle conflict and restricted airspace. Then, by preferencing speed change deconfliction maneuvers constrained by the vehicles flight envelope, vehicles can remain as close to the original planned path and prevent cascading vehicle to vehicle conflicts. Performing the search for a set of commands which can simultaneously ensure separation for each pair-wise aircraft interaction and optimize the total velocities of all the aircraft is further complicated by the fact that each aircraft's flight plan could contain multiple segments. This means that relative velocities will change when any aircraft achieves a waypoint and changes course. Additionally, the timing of when that aircraft will achieve a waypoint (or, more directly, the order upon which all of the aircraft will achieve their respective waypoints) will change with the commanded speed. Put all together, the continuous relative velocity of each vehicle pair and the discretized change in relative velocity at waypoints resembles a hybrid reachability problem - a form of control reachability. This paper proposes two methods for finding solutions to these multi-body problems. First, an analytical formulation of the continuous problem is developed with an exhaustive search of the combined state space. However, because of computational complexity, this technique is only computable for pairwise interactions. For more complicated scenarios, including the proposed 10 vehicle example, a discretized search space is used, and a depth-first search with early stopping is employed to find the first solution that solves the constraints.

Keywords: strategic planning, autonomous, aircraft, deconfliction

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Authors: Dorothy Kagazi

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The African elephant (Loxodonta africana) remains one of the most crop-damaging species around Kibale National Park, western Uganda. Elephant crop raiding deprives communities of food and incomes, consequently impacting livelihoods, attitude, and support for conservation. It also attracts an aggressive reaction from local communities including the retaliatory killing of a species that is already endangered and listed under Appendix I of the Convention on Endangered Species of Flora and Fauna (CITES). In order to mitigate against elephant crop raiding and minimize conflict, a number of interventions were devised by the government of Uganda such as physical guarding, scare-shooting, excavation of trenches, growing of unpalatable crops and fire lighting all of which have over the years been implemented around the park. These generated varying degrees of effectiveness but largely never solved the problem of elephants crossing into communities to destroy food and shelter which had a negative effect onto sustainable tourism of the communities who often resorted to killing these animals and hence contributing the falling numbers of these animals. It was until government discovered that there are far more effective ways of deterring these animals from crossing to communities that it commissioned a study to deploy the African honeybee (Apis mellifera scutellata) as a deterrent against elephant crop raiding and income enhancement for local people around the park. These efforts led to a number of projects around Kibale National Park where communities were facilitated to keep bees for human-elephant conflict mitigation and rural income enhancement through the sale of honey. These projects have registered tremendous success in reducing crop damage, enhance rural incomes, influence positive attitude change and ultimately secure community support for elephant and park conservation which is a clear manifestation of sustainable tourism development in the area. To address the issue of sustainability, the project was aligned with four major objectives that contributed to the overall goal of maintaining the areas around the parks and the national park itself in such a manner that it remains viable over an infinite period. Among these included determining deterrence effects of bees against elephant crop raiding, assessing the contribution of beekeeping towards rural income enhancement, determining the impact of community involvement of park conservation and management among others. The project deployed 500 improved hives by placing them at specific and previously identified and mapped out elephant crossing points along the park boundary. A control site was established without any intervention to facilitate comparison of findings and data was collected on elephant raiding frequency, patterns, honey harvested, and community attitude towards the park. A socio-economic assessment was also undertaken to ascertain the contribution of beekeeping to incomes and attitude change. In conclusion, human-wildlife conflicts have disturbed conservation and sustainable tourism development efforts. Such success stories like the beekeeping strategy should hence be extensively discussed and widely shared as a conservation technique for sustainable tourism.

Keywords: bees, communities, conservation, elephants

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Authors: Ricardo Alberto Chiong Zevallos, Eduardo Moraes Rego Reis

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Pancreatic adenocarcinoma (PDAC) patients have a less than 10% 5-year survival rate. PDAC has no defined diagnostic and prognostic biomarkers. Gemcitabine is the first-line drug in PDAC and several other cancers. Long non-coding RNAs (lncRNAs) contribute to the tumorigenesis and are potential biomarkers for PDAC. Although lncRNAs aren’t translated into proteins, they have important functions. LncRNAs can decoy or recruit proteins from the epigenetic machinery, act as microRNA sponges, participate in protein translocation through different cellular compartments, and even promote chemoresistance. The chromatin remodeling enzyme EZH2 is a histone methyltransferase that catalyzes the methylation of histone 3 at lysine 27, silencing local expression. EZH2 is ambivalent, it can also activate gene expression independently of its histone methyltransferase activity. EZH2 is overexpressed in several cancers and interacts with lncRNAs, being recruited to a specific locus. EZH2 can be recruited to activate an oncogene or silence a tumor suppressor. The lncRNAs misregulation in cancer can result in the differential recruitment of EZH2 and in a distinct epigenetic landscape, promoting chemoresistance. The relevance of the EZH2-lncRNAs interaction to chemoresistant PDAC was assessed by Real Time quantitative PCR (RT-qPCR) and RNA Immunoprecipitation (RIP) experiments with naïve and gemcitabine-resistant PDAC cells. The expression of several lncRNAs and EZH2 gene targets was evaluated contrasting naïve and resistant cells. Selection of candidate genes was made by bioinformatic analysis and literature curation. Indeed, the resistant cell line showed higher expression of chemoresistant-associated lncRNAs and protein coding genes. RIP detected lncRNAs interacting with EZH2 with varying intensity levels in the cell lines. During RIP, the nuclear fraction of the cells was incubated with an antibody for EZH2 and with magnetic beads. The RNA precipitated with the beads-antibody-EZH2 complex was isolated and reverse transcribed. The presence of candidate lncRNAs was detected by RT-qPCR, and the enrichment was calculated relative to INPUT (total lysate control sample collected before RIP). The enrichment levels varied across the several lncRNAs and cell lines. The EZH2-lncRNA interaction might be responsible for the regulation of chemoresistance-associated genes in multiple cancers. The relevance of the lncRNA-EZH2 interaction to PDAC was assessed by siRNA knockdown of a lncRNA, followed by the analysis of the EZH2 target expression by RT-qPCR. The chromatin immunoprecipitation (ChIP) of EZH2 and H3K27me3 followed by RT-qPCR with primers for EZH2 targets also assess the specificity of the EZH2 recruitment by the lncRNA. This is the first report of the interaction of EZH2 and lncRNAs HOTTIP and PVT1 in chemoresistant PDAC. HOTTIP and PVT1 were described as promoting chemoresistance in several cancers, but the role of EZH2 is not clarified. For the first time, the lncRNA LINC01133 was detected in a chemoresistant cancer. The interaction of EZH2 with LINC02577, LINC00920, LINC00941, and LINC01559 have never been reported in any context. The novel lncRNAs-EZH2 interactions regulate chemoresistant-associated genes in PDAC and might be relevant to other cancers. Therapies targeting EZH2 alone weren’t successful, and a combinatorial approach also targeting the lncRNAs interacting with it might be key to overcome chemoresistance in several cancers.

Keywords: epigenetics, chemoresistance, long non-coding RNAs, pancreatic cancer, histone modification

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Authors: Irina Mizeva, Elena Potapova, Viktor Dremin, Mikhail Mezentsev, Valeri Shupletsov

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The local tissue perfusion is regulated by the microvascular tone which is under the control of a number of physiological mechanisms. Laser Doppler flowmetry (LDF) together with wavelet analyses is the most commonly used technique to study the regulatory mechanisms of cutaneous microcirculation. External factors such as temperature, local pressure of the probe on the skin, etc. influence on the blood flow characteristics and are used as physiological tests to evaluate microvascular regulatory mechanisms. Local probe pressure influences on the microcirculation parameters measured by optical methods: diffuse reflectance spectroscopy, fluorescence spectroscopy, and LDF. Therefore, further study of probe pressure effects can be useful to improve the reliability of optical measurement. During pressure tests variation of the mean perfusion measured by means of LDF usually is estimated. An additional information concerning the physiological mechanisms of the vascular tone regulation system in response to local pressure can be obtained using spectral analyses of LDF samples. The aim of the present work was to develop protocol and algorithm of data processing appropriate for study physiological response to the local pressure test. Involving 6 subjects (20±2 years) and providing 5 measurements for every subject we estimated intersubject and-inter group variability of response of both averaged and oscillating parts of the LDF sample on external surface pressure. The final purpose of the work was to find special features which further can be used in wider clinic studies. The cutaneous perfusion measurements were carried out by LAKK-02 (SPE LAZMA Ltd., Russia), the skin loading was provided by the originally designed device which allows one to distribute the pressure around the LDF probe. The probe was installed on the dorsal part of the distal finger of the index figure. We collected measurements continuously for one hour and varied loading from 0 to 180mmHg stepwise with a step duration of 10 minutes. Further, we post-processed the samples using the wavelet transform and traced the energy of oscillations in five frequency bands over time. Weak loading leads to pressure-induced vasodilation, so one should take into account that the perfusion measured under pressure conditions will be overestimated. On the other hand, we revealed a decrease in endothelial associated fluctuations. Further loading (88 mmHg) induces amplification of pulsations in all frequency bands. We assume that such loading leads to a higher number of closed capillaries, higher input of arterioles in the LDF signal and as a consequence more vivid oscillations which mainly are formed in arterioles. External pressure higher than 144 mmHg leads to the decrease of oscillating components, after removing the loading very rapid restore of the tissue perfusion takes place. In this work, we have demonstrated that local skin loading influence on the microcirculation parameters measured by optic technique; this should be taken into account while developing portable electronic devices. The proposed protocol of local loading allows one to evaluate PIV as far as to trace dynamic of blood flow oscillations. This study was supported by the Russian Science Foundation under project N 18-15-00201.

Keywords: blood microcirculation, laser Doppler flowmetry, pressure-induced vasodilation, wavelet analyses blood

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Authors: Taghrid Asfar, Olusanya J. Oluwole, Michael Schmidt, Alejandra Casas, Zoran Bursac, Wasim Maziak.

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Waterpipe (WP) smoking (a.k.a. hookah) has increased dramatically in the US mainly due to the misperception that it is safer than cigarette smoking. Mounting evidence show that WP smoking is addictive and harmful. Health warning labels (HWLs) are effective in communicating smoking-related risks. Currently, the FDA requires that WP tobacco packages have a textual HWL about nicotine. While this represents a good step, it is inadequate given the established harm of WP smoking beyond addiction and the superior performance of pictorial HWLs over text-only ones. We developed 24 WP pictorial HWLs in a Delphi study among international expert panel. HWLs were grouped into 6 themes: addiction, harm compared to cigarettes, harm to others, health effects, quitting, and specific harms. This study aims to compare the effect of the pictorial HWLs compared to the FDA HWL, and 2) the effect of pictorial HWLs between the 6 themes. A 2x7 between/within subject online factorial experimental study was conducted among a national convenience sample of 300 (50% current WP smokers; 50% nonsmokers) US adults (females 71.1%; mean age of 31.1±3.41 years) in March 2022. The first factor varied WP smoking status (smokers, nonsmokers). The second factor varied the HWL theme and type (text, pictorial). Participants were randomized to view and rate 7 HWLs: 1 FDA text HWL (control) and 6 HWLs, one from each of the 6 themes, all presented in random order. HWLs were rated based on the message impact framework into five categories: attention, reaction (believability, relevance, fear), perceived effectiveness, intentions to quit WP among current smokers, and intention to not initiate WP among nonsmokers. measures were assessed on a 5-point Likert scale (1=not at all to 5=very much) for attention and reaction and on a 7-point Likert scale (1=not at all to 7=very much) for the perceived effectiveness and intentions to quit or not initiate WP smoking. Means and SDs of outcome measures for each HWL type and theme were calculated. Planned comparisons using Friedman test followed by pairwise Wilcoxon signed-rank test for multiple comparisons were used to examine distributional differences of outcomes between the HWL type and themes. Approximately 74.4 % of participants were non-Hispanic Whites, 68.4% had college degrees, and 41.5% were under the poverty level. Participants reported starting WTS on average at 20.3±8.19 years. Compared with the FDA text HWL, pictorial HWLs elicited higher attention (p<0.0001), fear (p<0.0001), harm perception (p<0.0003), perceived effectiveness (p<0.0001), and intentions to quit (p=0.0014) and not initiate WP smoking (p<0.0003). HWLs in theme 3 (harm to others) achieved the highest rating in attention (4.14±1), believability (4.15±0.95), overall perceived effectiveness (7.60±2.35), harm perception (7.53±2.43), and intentions to quit (7.35±2.57). HWLs in theme 2 (WP harm compared to cigarettes) achieved the highest rating in discouraging WP smoking initiation (7.32±2.54). Pictorial HWLs were superior to the FDA text-only for several communication outcomes. Pictorial HWLs related to WP harm to others and WP harm compared to cigarette are promising. These findings provide strong evidence for the potential implementation of WP-specific pictorial HWLs.

Keywords: health communication, waterpipe smoking, factorial experiment, reaction, harm perception, tobacco regulations

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