Search results for: Hospital information system
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Search results for: Hospital information system

74 A Systemic Review and Comparison of Non-Isolated Bi-Directional Converters

Authors: Rahil Bahrami, Kaveh Ashenayi

Abstract:

This paper presents a systematic classification and comparative analysis of non-isolated bi-directional DC-DC converters. The increasing demand for efficient energy conversion in diverse applications has spurred the development of various converter topologies. In this study, we categorize bi-directional converters into three distinct classes: Inverting, Non-Inverting, and Interleaved. Each category is characterized by its unique operational characteristics and benefits. Furthermore, a practical comparison is conducted by evaluating the results of simulation of each bi-directional converter. BDCs can be classified into isolated and non-isolated topologies. Non-isolated converters share a common ground between input and output, making them suitable for applications with minimal voltage change. They are easy to integrate, lightweight, and cost-effective but have limitations like limited voltage gain, switching losses, and no protection against high voltages. Isolated converters use transformers to separate input and output, offering safety benefits, high voltage gain, and noise reduction. They are larger and more costly but are essential for automotive designs where safety is crucial. The paper focuses on non-isolated systems.The paper discusses the classification of non-isolated bidirectional converters based on several criteria. Common factors used for classification include topology, voltage conversion, control strategy, power capacity, voltage range, and application. These factors serve as a foundation for categorizing converters, although the specific scheme might vary depending on contextual, application, or system-specific requirements. The paper presents a three-category classification for non-isolated bi-directional DC-DC converters: inverting, non-inverting, and interleaved. In the inverting category, converters produce an output voltage with reversed polarity compared to the input voltage, achieved through specific circuit configurations and control strategies. This is valuable in applications such as motor control and grid-tied solar systems. The non-inverting category consists of converters maintaining the same voltage polarity, useful in scenarios like battery equalization. Lastly, the interleaved category employs parallel converter stages to enhance power delivery and reduce current ripple. This classification framework enhances comprehension and analysis of non-isolated bi-directional DC-DC converters. The findings contribute to a deeper understanding of the trade-offs and merits associated with different converter types. As a result, this work aids researchers, practitioners, and engineers in selecting appropriate bi-directional converter solutions for specific energy conversion requirements. The proposed classification framework and experimental assessment collectively enhance the comprehension of non-isolated bi-directional DC-DC converters, fostering advancements in efficient power management and utilization.The simulation process involves the utilization of PSIM to model and simulate non-isolated bi-directional converter from both inverted and non-inverted category. The aim is to conduct a comprehensive comparative analysis of these converters, considering key performance indicators such as rise time, efficiency, ripple factor, and maximum error. This systematic evaluation provides valuable insights into the dynamic response, energy efficiency, output stability, and overall precision of the converters. The results of this comparison facilitate informed decision-making and potential optimizations, ensuring that the chosen converter configuration aligns effectively with the designated operational criteria and performance goals.

Keywords: bi-directional, DC-DC converter, non-isolated, energy conversion

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73 Biochemical and Antiviral Study of Peptides Isolated from Amaranthus hypochondriacus on Tomato Yellow Leaf Curl Virus Replication

Authors: José Silvestre Mendoza Figueroa, Anders Kvarnheden, Jesús Méndez Lozano, Edgar Antonio Rodríguez Negrete, Manuel Soriano García

Abstract:

Agroindustrial plants such as cereals and pseudo cereals offer a substantial source of biomacromolecules, as they contain large amounts per tissue-gram of proteins, polysaccharides and lipids in comparison with other plants. In particular, Amaranthus hypochondriacus seeds have high levels of proteins in comparison with other cereal and pseudo cereal species, which makes the plant a good source of bioactive molecules such as peptides. Geminiviruses are one principal class of pathogens that causes important economic losses in crops, affecting directly the development and production of the plant. One such virus is the Tomato yellow leaf curl virus (TYLCV), which affects mainly Solanacea family plants such as tomato species. The symptoms of the disease are curling of leaves, chlorosis, dwarfing and floral abortion. The aim of this work was to get peptides derived from enzymatic hydrolysis of globulins and albumins from amaranth seeds with specific recognition of the replication origin in the TYLCV genome, and to test the antiviral activity on host plants with the idea to generate a direct control of this viral infection. Globulins and albumins from amaranth were extracted, the fraction was enzymatically digested with papain, and the aromatic peptides fraction was selected for further purification. Six peptides were tested against the replication origin (OR) using affinity assays, surface resonance plasmon and fluorescent titration, and two of these peptides showed high affinity values to the replication origin of the virus, dissociation constant values were calculated and showed specific interaction between the peptide Ampep1 and the OR. An in vitro replication test of the total TYLCV DNA was performed, in which the peptide AmPep1 was added in different concentrations to the system reaction, which resulted in a decrease of viral DNA synthesis when the peptide concentration increased. Also, we showed that the peptide can decrease the complementary DNA chain of the virus in Nicotiana benthamiana leaves, confirming that the peptide binds to the OR and that its expected mechanism of action is to decrease the replication rate of the viral genome. In an infection assay, N. benthamiana plants were agroinfected with TYLCV-Israel and TYLCV-Guasave. After confirming systemic infection, the peptide was infiltrated in new infected leaves, and the plants treated with the peptide showed a decrease of virus symptoms and viral titer. In order to confirm the antiviral activity in a commercial crop, tomato plants were infected with TYLCV. After confirming systemic infection, plants were infiltrated with peptide solution as above, and the symptom development was monitored 21 days after treatment, showing that tomato plants treated with peptides had lower symptom rates and viral titer. The peptide was also tested against other begomovirus such as Pepper huasteco yellow vein virus (PHYVV-Guasave), showing a decrease of symptoms in N. benthamiana infected plants. The model of direct biochemical control of TYLCV infection shown in this work can be extrapolated to other begomovirus infections, and the methods reported here can be used for design of antiviral agrochemicals for other plant virus infections.

Keywords: agrochemical screening, antiviral, begomovirus, geminivirus, peptides, plasmon, TYLCV

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72 Evaluating Viability of Using South African Forestry Process Biomass Waste Mixtures as an Alternative Pyrolysis Feedstock in the Production of Bio Oil

Authors: Thembelihle Portia Lubisi, Malusi Ntandoyenkosi Mkhize, Jonas Kalebe Johakimu

Abstract:

Fertilizers play an important role in maintaining the productivity and quality of plants. Inorganic fertilizers (containing nitrogen, phosphorus, and potassium) are largely used in South Africa as they are considered inexpensive and highly productive. When applied, a portion of the excess fertilizer will be retained in the soil, a portion enters water streams due to surface runoff or the irrigation system adopted. Excess nutrient from the fertilizers entering the water stream eventually results harmful algal blooms (HABs) in freshwater systems, which not only disrupt wildlife but can also produce toxins harmful to humans. Use of agro-chemicals such as pesticides and herbicides has been associated with increased antimicrobial resistance (AMR) in humans as the plants are consumed by humans. This resistance of bacterial poses a threat as it prevents the Health sector from being able to treat infectious disease. Archaeological studies have found that pyrolysis liquids were already used in the time of the Neanderthal as a biocide and plant protection product. Pyrolysis is thermal degradation process of plant biomass or organic material under anaerobic conditions leading to production of char, bio-oils and syn gases. Bio-oil constituents can be categorized as water soluble (wood vinegar) and water insoluble fractions (tar and light oils). Wood vinegar (pyro-ligneous acid) is said to contain contains highly oxygenated compounds including acids, alcohols, aldehydes, ketones, phenols, esters, furans, and other multifunctional compounds with various molecular weights and compositions depending on the biomass material derived from and pyrolysis operating conditions. Various researchers have found the wood vinegar to be efficient in the eradication of termites, effective in plant protection and plant growth, has antibacterial characteristics and was found effective in inhibiting the micro-organisms such as candida yeast, E-coli, etc. This study investigated characterisation of South African forestry product processing waste with intention of evaluating the potential of using the respective biomass waste as feedstock for boil oil production via pyrolysis process. Ability to use biomass waste materials in production of wood-vinegar has advantages that it does not only allows for reduction of environmental pollution and landfill requirement, but it also does not negatively affect food security. The biomass wastes investigated were from the popular tree types in KZN, which are, pine saw dust (PSD), pine bark (PB), eucalyptus saw dust (ESD) and eucalyptus bark (EB). Furthermore, the research investigates the possibility of mixing the different wastes with an aim to lessen the cost of raw material separation prior to feeding into pyrolysis process and mixing also increases the amount of biomass material available for beneficiation. A 50/50 mixture of PSD and ESD (EPSD) and mixture containing pine saw dust; eucalyptus saw dust, pine bark and eucalyptus bark (EPSDB). Characterisation of the biomass waste will look at analysis such as proximate (volatiles, ash, fixed carbon), ultimate (carbon, hydrogen, nitrogen, oxygen, sulphur), high heating value, structural (cellulose, hemicellulose and lignin) and thermogravimetric analysis.

Keywords: characterisation, biomass waste, saw dust, wood waste

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71 Septic Pulmonary Emboli as a Complication of Peripheral Venous Cannula Insertion

Authors: Ankita Baidya, Vanishri Ganakumar, Ranveer S. Jadon, Piyush Ranjan, Rita Sood

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Septic embolism can have varied presentations and clinical considerations. Infected central venous catheters are commonly associated with septic emboli but peripheral vascular catheters are rarely implicated. We describe a rare case of septic pulmonary emboli related to infected peripheral venous cannulation caused by an unusual etiological agent. A young male presented with complaints of fever, productive cough, sudden onset shortness of breath and cellulitis in both the upper limbs. He was recently hospitalised for dengue fever and administered intravenous fluids through peripheral venous line. The patient was febrile, tachypneic and in respiratory distress, there were multiple pus filled bullae in left hand alongwith swelling and erythema involving right forearm that started at the site of cannulation. Chest examination showed active accessory muscles of respiration, stony dull percussion at the base of right lung and decreased breath sounds at right infrascapular, infraaxillary and mammary area. Other system examination was within normal limits. Chest X-ray revealed bilateral multiple patchy heterogenous peripheral opacities and infiltrates with right-sided pleural effusion. Contrast-enhanced computed tomography (CECT) chest showed feeding vessel sign confirming the diagnosis as septic emboli. Venous Doppler and 2D-echocardiogarm were normal. Laboratory findings showed marked leucocytosis (22000/mm3). Pus aspirate, blood sample, and sputum sample were sent for microbiological testing. The patient was started empirically on ceftriaxone, vancomycin, and clindamycin. The Pus culture and sputum culture showed Klebsiella pneumoniae sensitive to cefoperazone-sulbactum, piperacillin-tazobactum, meropenem and amikacin. The antibiotics were modified accordingly to antimicrobial sensitivity profile to Cefoperazone-sulbactum. Bronchoalveolar lavage (BAL) was done and sent for microbiological investigations. BAL culture showed Klebsiella pneumoniae with same antimicrobial resistance profile. On day 6 of starting cefoperazone-sulbactum, he became afebrile. The skin lesions improved significantly. He was administered 2 weeks of cefoperazone–sulbactum and discharged on oral faropenem for 4 weeks. At the time of discharge, TLC was 11200/mm3 with marked radiological resolution of infection and healed skin lesions. He was kept in regular follow up. Chest X-ray and skin lesions showed complete resolution after 8 weeks. Till date, only couple of case reports of septic emboli through peripheral intravenous line have been reported in English literature. This case highlights that a simple procedure of peripheral intravenous cannulation can lead to catastrophic complication of septic pulmonary emboli and widespread cellulitis if not done with proper care and precautions. Also, the usual pathogens in such clinical settings are gram positive bacteria, but with the history of recent hospitalization, empirical therapy should also cover drug resistant gram negative microorganisms. It also emphasise the importance of appropriate healthcare practices to be taken care during all procedures.

Keywords: antibiotics, cannula, Klebsiella pneumoniae, septic emboli

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70 Developing a Place-Name Gazetteer for Singapore by Mining Historical Planning Archives and Selective Crowd-Sourcing

Authors: Kevin F. Hsu, Alvin Chua, Sarah X. Lin

Abstract:

As a multilingual society, Singaporean names for different parts of the city have changed over time. Residents included Indigenous Malays, dialect-speakers from China, European settler-colonists, and Tamil-speakers from South India. Each group would name locations in their own languages. Today, as ancestral tongues are increasingly supplanted by English, contemporary Singaporeans’ understanding of once-common place names is disappearing. After demolition or redevelopment, some urban places will only exist in archival records or in human memory. United Nations conferences on the standardization of geographic names have called attention to how place names relate to identity, well-being, and a sense of belonging. The Singapore Place-Naming Project responds to these imperatives by capturing past and present place names through digitizing historical maps, mining archival records, and applying selective crowd-sourcing to trace the evolution of place names throughout the city. The project ensures that both formal and vernacular geographical names remain accessible to historians, city planners, and the public. The project is compiling a gazetteer, a geospatial archive of placenames, with streets, buildings, landmarks, and other points of interest (POI) appearing in the historic maps and planning documents of Singapore, currently held by the National Archives of Singapore, the National Library Board, university departments, and the Urban Redevelopment Authority. To create a spatial layer of information, the project links each place name to either a geo-referenced point, line segment, or polygon, along with the original source material in which the name appears. This record is supplemented by crowd-sourced contributions from civil service officers and heritage specialists, drawing from their collective memory to (1) define geospatial boundaries of historic places that appear in past documents, but maybe unfamiliar to users today, and (2) identify and record vernacular place names not captured in formal planning documents. An intuitive interface allows participants to demarcate feature classes, vernacular phrasings, time periods, and other knowledge related to historical or forgotten spaces. Participants are stratified into age bands and ethnicity to improve representativeness. Future iterations could allow additional public contributions. Names reveal meanings that communities assign to each place. While existing historical maps of Singapore allow users to toggle between present-day and historical raster files, this project goes a step further by adding layers of social understanding and planning documents. Tracking place names illuminates linguistic, cultural, commercial, and demographic shifts in Singapore, in the context of transformations of the urban environment. The project also demonstrates how a moderated, selectively crowd-sourced effort can solicit useful geospatial data at scale, sourced from different generations, and at higher granularity than traditional surveys, while mitigating negative impacts of unmoderated crowd-sourcing. Stakeholder agencies believe the project will achieve several objectives, including Supporting heritage conservation and public education; Safeguarding intangible cultural heritage; Providing historical context for street, place or development-renaming requests; Enhancing place-making with deeper historical knowledge; Facilitating emergency and social services by tagging legal addresses to vernacular place names; Encouraging public engagement with heritage by eliciting multi-stakeholder input.

Keywords: collective memory, crowd-sourced, digital heritage, geospatial, geographical names, linguistic heritage, place-naming, Singapore, Southeast Asia

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69 Production of Insulin Analogue SCI-57 by Transient Expression in Nicotiana benthamiana

Authors: Adriana Muñoz-Talavera, Ana Rosa Rincón-Sánchez, Abraham Escobedo-Moratilla, María Cristina Islas-Carbajal, Miguel Ángel Gómez-Lim

Abstract:

The highest rates of diabetes incidence and prevalence worldwide will increase the number of diabetic patients requiring insulin or insulin analogues. Then, current production systems would not be sufficient to meet the future market demands. Therefore, developing efficient expression systems for insulin and insulin analogues are needed. In addition, insulin analogues with better pharmacokinetics and pharmacodynamics properties and without mitogenic potential will be required. SCI-57 (single chain insulin-57) is an insulin analogue having 10 times greater affinity to the insulin receptor, higher resistance to thermal degradation than insulin, native mitogenicity and biological effect. Plants as expression platforms have been used to produce recombinant proteins because of their advantages such as cost-effectiveness, posttranslational modifications, absence of human pathogens and high quality. Immunoglobulin production with a yield of 50% has been achieved by transient expression in Nicotiana benthamiana (Nb). The aim of this study is to produce SCI-57 by transient expression in Nb. Methodology: DNA sequence encoding SCI-57 was cloned in pICH31070. This construction was introduced into Agrobacterium tumefaciens by electroporation. The resulting strain was used to infiltrate leaves of Nb. In order to isolate SCI-57, leaves from transformed plants were incubated 3 hours with the extraction buffer therefore filtrated to remove solid material. The resultant protein solution was subjected to anion exchange chromatography on an FPLC system and ultrafiltration to purify SCI-57. Detection of SCI-57 was made by electrophoresis pattern (SDS-PAGE). Protein band was digested with trypsin and the peptides were analyzed by Liquid chromatography tandem-mass spectrometry (LC-MS/MS). A purified protein sample (20µM) was analyzed by ESI-Q-TOF-MS to obtain the ionization pattern and the exact molecular weight determination. Chromatography pattern and impurities detection were performed using RP-HPLC using recombinant insulin as standard. The identity of the SCI-57 was confirmed by anti-insulin ELISA. The total soluble protein concentration was quantified by Bradford assay. Results: The expression cassette was verified by restriction mapping (5393 bp fragment). The SDS-PAGE of crude leaf extract (CLE) of transformed plants, revealed a protein of about 6.4 kDa, non-present in CLE of untransformed plants. The LC-MS/MS results displayed one peptide with a high score that matches SCI-57 amino acid sequence in the sample, confirming the identity of SCI-57. From the purified SCI-57 sample (PSCI-57) the most intense charge state was 1069 m/z (+6) on the displayed ionization pattern corresponding to the molecular weight of SCI-57 (6412.6554 Da). The RP-HPLC of the PSCI-57 shows the presence of a peak with similar retention time (rt) and UV spectroscopic profile to the insulin standard (SCI-57 rt=12.96 and insulin rt=12.70 min). The collected SCI-57 peak had ELISA signal. The total protein amount in CLE from transformed plants was higher compared to untransformed plants. Conclusions: Our results suggest the feasibility to produce insulin analogue SCI-57 by transient expression in Nicotiana benthamiana. Further work is being undertaken to evaluate the biological activity by glucose uptake by insulin-sensitive and insulin-resistant murine and human cultured adipocytes.

Keywords: insulin analogue, mass spectrometry, Nicotiana benthamiana, transient expression

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68 Full Characterization of Heterogeneous Antibody Samples under Denaturing and Native Conditions on a Hybrid Quadrupole-Orbitrap Mass Spectrometer

Authors: Rowan Moore, Kai Scheffler, Eugen Damoc, Jennifer Sutton, Aaron Bailey, Stephane Houel, Simon Cubbon, Jonathan Josephs

Abstract:

Purpose: MS analysis of monoclonal antibodies (mAbs) at the protein and peptide levels is critical during development and production of biopharmaceuticals. The compositions of current generation therapeutic proteins are often complex due to various modifications which may affect efficacy. Intact proteins analyzed by MS are detected in higher charge states that also provide more complexity in mass spectra. Protein analysis in native or native-like conditions with zero or minimal organic solvent and neutral or weakly acidic pH decreases charge state value resulting in mAb detection at higher m/z ranges with more spatial resolution. Methods: Three commercially available mAbs were used for all experiments. Intact proteins were desalted online using size exclusion chromatography (SEC) or reversed phase chromatography coupled on-line with a mass spectrometer. For streamlined use of the LC- MS platform we used a single SEC column and alternately selected specific mobile phases to perform separations in either denaturing or native-like conditions: buffer A (20 % ACN, 0.1 % FA) with Buffer B (100 mM ammonium acetate). For peptide analysis mAbs were proteolytically digested with and without prior reduction and alkylation. The mass spectrometer used for all experiments was a commercially available Thermo Scientific™ hybrid Quadrupole-Orbitrap™ mass spectrometer, equipped with the new BioPharma option which includes a new High Mass Range (HMR) mode that allows for improved high mass transmission and mass detection up to 8000 m/z. Results: We have analyzed the profiles of three mAbs under reducing and native conditions by direct infusion with offline desalting and with on-line desalting via size exclusion and reversed phase type columns. The presence of high salt under denaturing conditions was found to influence the observed charge state envelope and impact mass accuracy after spectral deconvolution. The significantly lower charge states observed under native conditions improves the spatial resolution of protein signals and has significant benefits for the analysis of antibody mixtures, e.g. lysine variants, degradants or sequence variants. This type of analysis requires the detection of masses beyond the standard mass range ranging up to 6000 m/z requiring the extended capabilities available in the new HMR mode. We have compared each antibody sample that was analyzed individually with mixtures in various relative concentrations. For this type of analysis, we observed that apparent native structures persist and ESI is benefited by the addition of low amounts of acetonitrile and formic acid in combination with the ammonium acetate-buffered mobile phase. For analyses on the peptide level we analyzed reduced/alkylated, and non-reduced proteolytic digests of the individual antibodies separated via reversed phase chromatography aiming to retrieve as much information as possible regarding sequence coverage, disulfide bridges, post-translational modifications such as various glycans, sequence variants, and their relative quantification. All data acquired were submitted to a single software package for analysis aiming to obtain a complete picture of the molecules analyzed. Here we demonstrate the capabilities of the mass spectrometer to fully characterize homogeneous and heterogeneous therapeutic proteins on one single platform. Conclusion: Full characterization of heterogeneous intact protein mixtures by improved mass separation on a quadrupole-Orbitrap™ mass spectrometer with extended capabilities has been demonstrated.

Keywords: disulfide bond analysis, intact analysis, native analysis, mass spectrometry, monoclonal antibodies, peptide mapping, post-translational modifications, sequence variants, size exclusion chromatography, therapeutic protein analysis, UHPLC

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67 Clinical Efficacy of Localized Salvage Prostate Cancer Reirradiation with Proton Scanning Beam Therapy

Authors: Charles Shang, Salina Ramirez, Stephen Shang, Maria Estrada, Timothy R. Williams

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Purpose: Over the past decade, proton therapy utilizing pencil beam scanning has emerged as a preferred treatment modality in radiation oncology, particularly for prostate cancer. This retrospective study aims to assess the clinical and radiobiological efficacy of proton scanning beam therapy in the treatment of localized salvage prostate cancer, following initial radiation therapy with a different modality. Despite the previously delivered high radiation doses, this investigation explores the potential of proton reirradiation in controlling recurrent prostate cancer and detrimental quality of life side effects. Methods and Materials: A retrospective analysis was conducted on 45 cases of locally recurrent prostate cancer that underwent salvage proton reirradiation. Patients were followed for 24.6 ± 13.1 months post-treatment. These patients had experienced an average remission of 8.5 ± 7.9 years after definitive radiotherapy for localized prostate cancer (n=41) or post-prostatectomy (n=4), followed by rising PSA levels. Recurrent disease was confirmed by FDG-PET (n=31), PSMA-PET (n=10), or positive local biopsy (n=4). Gross tumor volume (GTV) was delineated based on PET and MR imaging, with the planning target volume (PTV) expanding to an average of 10.9 cm³. Patients received proton reirradiation using two oblique coplanar beams, delivering total doses ranging from 30.06 to 60.00 GyE in 17–30 fractions. All treatments were administered using the ProBeam Compact system with CT image guidance. The International Prostate Symptom Scores (IPSS) and prostate-specific antigen (PSA) levels were evaluated to assess treatment-related toxicity and tumor control. Results and Discussions: In this cohort (mean age: 76.7 ± 7.3 years), 60% (27/45) of patients showed sustained reductions in PSA levels post-treatment, while 36% (16/45) experienced a PSA decline of more than 0.8 ng/mL. Additionally, 73% (33/45) of patients exhibited an initial PSA reduction, though some showed later PSA increases, indicating the potential presence of undetected metastatic lesions. The median post-retreatment IPSS score was 4, significantly lower than scores reported in other treatment studies. Overall, 69% of patients reported mild urinary symptoms, with 96% (43/45) experiencing mild to moderate symptoms. Three patients experienced grade I or II proctitis, while one patient reported grade III proctitis. These findings suggest that regional organs, including the urethra, bladder, and rectum, demonstrate significant radiobiological recovery from prior radiation exposure, enabling tolerance to additional proton scanning beam therapy. Conclusions: This retrospective analysis of 45 patients with recurrent localized prostate cancer treated with salvage proton reirradiation demonstrates favorable outcomes, with a median follow-up of two years. The post-retreatment IPSS scores were comparable to those reported in follow-up studies of initial radiation therapy treatments, indicating stable or improved urinary symptoms compared to the end of initial treatment. These results highlight the efficacy of proton scanning beam therapy in providing effective salvage treatment while minimizing adverse effects on critical organs. The findings also enhance the understanding of radiobiological responses to reirradiation and support proton therapy as a viable option for patients with recurrent localized prostate cancer following previous definitive radiation therapy.

Keywords: prostate salvage radiotherapy, proton therapy, biological radiation tolerance, radiobiology of organs

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66 Challenging Airway Management for Tracheal Compression Due to a Rhabdomyosarcoma

Authors: Elena Parmentier, Henrik Endeman

Abstract:

Introduction: Large mediastinal masses often present with diagnostic and clinical challenges due to compression of the respiratory and hemodynamic system. We present a case of a mediastinal mass with symptomatic mechanical compression of the trachea, resulting in challenging airway management. Methods: We present a case of 66-year-old male, complaining of progressive dysphagia. Initial esophagogastroscopy revealed a stenosis secondary to external compression, biopsies were inconclusive. Additional CT scan showed a large mediastinal mass of unknown origin, situated between the vertebrae and esophagus. Symptoms progressed and patient developed dyspnea and stridor. A new CT showed quick growth of the mass with compression of the trachea, subglottic to just above the carina. A tracheal covered stent was successfully placed. Endobronchial ultrasound revealed a large irregular mass without tracheal invasion, biopsies were taken. 4 days after stent placement, the patients’ condition deteriorated with worsening of stridor, dyspnea and desaturation. Migration of the tracheal stent into the right main bronchus was seen on chest X ray, with obstruction of the left main bronchus and secondary atelectasis. Different methods have been described in the literature for tracheobronchial stent removal (surgical, endoscopic, fluoroscopyguided), our first choice in this case was flexible bronchoscopy. However, this revealed tracheal compression above the migrated stent and passage of the scope occurred impossible. Patient was admitted to the ICU, high-flow nasal oxygen therapy was started and the situation stabilized, giving time for extensive assessment and preparation of the airway management approach. Close cooperation between the intensivist, pulmonologist, anesthesiologist and otorhinolaryngologist was essential. Results: In case of sudden deterioration, a protocol for emergency situations was made. Given the increased risk of additional tracheal compression after administration of neuromuscular blocking agents, an approach with awake fiberoptic intubation maintaining spontaneous ventilation was proposed. However, intubation without retrieval of the tracheal stent was found undesirable due to expected massive shunting over the left atelectatic lung. As rescue option, assistance of extracorporeal circulation was considered and perfusionist was kept on standby. The patient stayed stable and was transferred to the operating theatre. High frequency jet ventilation under general anesthesia resulted in desaturations up to 50%, making rigid bronchoscopy impossible. Subsequently an endotracheal tube size 8 could be placed successfully and the stent could be retrieved via bronchoscopy over (and with) the tube, after which the patient was reintubated. Finally, a tracheostomy (Shiley™ Tracheostomy Tube With Cuff, size 8) was placed, fiberoptic control showed a patent airway. Patient was readmitted to the ICU and could be quickly weaned of the ventilator. Pathology was positive for rhabdomyosarcoma, without indication for systemic therapy. Extensive surgery (laryngectomy, esophagectomy) was suggested, but patient refused and palliative care was started. Conclusion: Due to meticulous planning in an interdisciplinary team, we showed a successful airway management approach in this complicated case of critical airway compression secondary to a rare rhabdomyosarcoma, complicated by tracheal stent migration. Besides presenting our thoughts and considerations, we support exploring other possible approaches of this specific clinical problem.

Keywords: airway management, rhabdomyosarcoma, stent displacement, tracheal stenosis

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65 Trajectory Optimization for Autonomous Deep Space Missions

Authors: Anne Schattel, Mitja Echim, Christof Büskens

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Trajectory planning for deep space missions has become a recent topic of great interest. Flying to space objects like asteroids provides two main challenges. One is to find rare earth elements, the other to gain scientific knowledge of the origin of the world. Due to the enormous spatial distances such explorer missions have to be performed unmanned and autonomously. The mathematical field of optimization and optimal control can be used to realize autonomous missions while protecting recourses and making them safer. The resulting algorithms may be applied to other, earth-bound applications like e.g. deep sea navigation and autonomous driving as well. The project KaNaRiA ('Kognitionsbasierte, autonome Navigation am Beispiel des Ressourcenabbaus im All') investigates the possibilities of cognitive autonomous navigation on the example of an asteroid mining mission, including the cruise phase and approach as well as the asteroid rendezvous, landing and surface exploration. To verify and test all methods an interactive, real-time capable simulation using virtual reality is developed under KaNaRiA. This paper focuses on the specific challenge of the guidance during the cruise phase of the spacecraft, i.e. trajectory optimization and optimal control, including first solutions and results. In principle there exist two ways to solve optimal control problems (OCPs), the so called indirect and direct methods. The indirect methods are being studied since several decades and their usage needs advanced skills regarding optimal control theory. The main idea of direct approaches, also known as transcription techniques, is to transform the infinite-dimensional OCP into a finite-dimensional non-linear optimization problem (NLP) via discretization of states and controls. These direct methods are applied in this paper. The resulting high dimensional NLP with constraints can be solved efficiently by special NLP methods, e.g. sequential quadratic programming (SQP) or interior point methods (IP). The movement of the spacecraft due to gravitational influences of the sun and other planets, as well as the thrust commands, is described through ordinary differential equations (ODEs). The competitive mission aims like short flight times and low energy consumption are considered by using a multi-criteria objective function. The resulting non-linear high-dimensional optimization problems are solved by using the software package WORHP ('We Optimize Really Huge Problems'), a software routine combining SQP at an outer level and IP to solve underlying quadratic subproblems. An application-adapted model of impulsive thrusting, as well as a model of an electrically powered spacecraft propulsion system, is introduced. Different priorities and possibilities of a space mission regarding energy cost and flight time duration are investigated by choosing different weighting factors for the multi-criteria objective function. Varying mission trajectories are analyzed and compared, both aiming at different destination asteroids and using different propulsion systems. For the transcription, the robust method of full discretization is used. The results strengthen the need for trajectory optimization as a foundation for autonomous decision making during deep space missions. Simultaneously they show the enormous increase in possibilities for flight maneuvers by being able to consider different and opposite mission objectives.

Keywords: deep space navigation, guidance, multi-objective, non-linear optimization, optimal control, trajectory planning.

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64 Hydrocarbon Source Rocks of the Maragh Low

Authors: Elhadi Nasr, Ibrahim Ramadan

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Biostratigraphical analyses of well sections from the Maragh Low in the Eastern Sirt Basin has allowed high resolution correlations to be undertaken. Full integration of this data with available palaeoenvironmental, lithological, gravity, seismic, aeromagnetic, igneous, radiometric and wireline log information and a geochemical analysis of source rock quality and distribution has led to a more detailed understanding of the geological and the structural history of this area. Pre Sirt Unconformity two superimposed rifting cycles have been identified. The oldest is represented by the Amal Group of sediments and is of Late Carboniferous, Kasimovian / Gzelian to Middle Triassic, Anisian age. Unconformably overlying is a younger rift cycle which is represented the Sarir Group of sediments and is of Early Cretaceous, late Neocomian to Aptian in age. Overlying the Sirt Unconformity is the marine Late Cretaceous section. An assessment of pyrolysis results and a palynofacies analysis has allowed hydrocarbon source facies and quality to be determined. There are a number of hydrocarbon source rock horizons in the Maragh Low, these are sometimes vertically stacked and they are of fair to excellent quality. The oldest identified source rock is the Triassic Shale, this unit is unconformably overlain by sandstones belonging to the Sarir Group and conformably overlies a Triassic Siltstone unit. Palynological dating of the Triassic Shale unit indicates a Middle Triassic, Anisian age. The Triassic Shale is interpreted to have been deposited in a lacustrine palaeoenvironment. This particularly is evidenced by the dark, fine grained, organic rich nature of the sediment and is supported by palynofacies analysis and by the recovery of fish fossils. Geochemical analysis of the Triassic Shale indicates total organic carbon varying between 1.37 and 3.53. S2 pyrolysate yields vary between 2.15 mg/g and 6.61 mg/g and hydrogen indices vary between 156.91 and 278.91. The source quality of the Triassic Shale varies from being of fair to very good / rich. Linked to thermal maturity it is now a very good source for light oil and gas. It was once a very good to rich oil source. The Early Barremian Shale was also deposited in a lacustrine palaeoenvironment. Recovered palynomorphs indicate an Early Cretaceous, late Neocomian to early Barremian age. The Early Barremian Shale is conformably underlain and overlain by sandstone units belonging to the Sarir Group of sediments which are also of Early Cretaceous age. Geochemical analysis of the Early Barremian Shale indicates that it is a good oil source and was originally very good. Total organic carbon varies between 3.59% and 7%. S2 varies between 6.30 mg/g and 10.39 mg/g and the hydrogen indices vary between 148.4 and 175.5. A Late Barremian Shale unit of this age has also been identified in the central Maragh Low. Geochemical analyses indicate that total organic carbon varies between 1.05 and 2.38%, S2 pyrolysate between 1.6 and 5.34 mg/g and the hydrogen index between 152.4 and 224.4. It is a good oil source rock which is now mature. In addition to the non marine hydrocarbon source rocks pre Sirt Unconformity, three formations in the overlying Late Cretaceous section also provide hydrocarbon quality source rocks. Interbedded shales within the Rachmat Formation of Late Cretaceous, early Campanian age have total organic carbon ranging between, 0.7 and 1.47%, S2 pyrolysate varying between 1.37 and 4.00 mg/g and hydrogen indices varying between 195.7 and 272.1. The indication is that this unit would provide a fair gas source to a good oil source. Geochemical analyses of the overlying Tagrifet Limestone indicate that total organic carbon varies between 0.26% and 1.01%. S2 pyrolysate varies between 1.21 and 2.16 mg/g and hydrogen indices vary between 195.7 and 465.4. For the overlying Sirt Shale Formation of Late Cretaceous, late Campanian age, total organic carbon varies between 1.04% and 1.51%, S2 pyrolysate varies between 4.65 mg/g and 6.99 mg/g and the hydrogen indices vary between 151 and 462.9. The study has proven that both the Sirt Shale Formation and the Tagrifet Limestone are good to very good and rich sources for oil in the Maragh Low. High resolution biostratigraphical interpretations have been integrated and calibrated with thermal maturity determinations (Vitrinite Reflectance (%Ro), Spore Colour Index (SCI) and Tmax (ºC) and the determined present day geothermal gradient of 25ºC / Km for the Maragh Low. Interpretation of generated basin modelling profiles allows a detailed prediction of timing of maturation development of these source horizons and leads to a determination of amounts of missing section at major unconformities. From the results the top of the oil window (0.72% Ro) is picked as high as 10,700’ and the base of the oil window (1.35% Ro) assuming a linear trend and by projection is picked as low as 18,000’ in the Maragh Low. For the Triassic Shale the early phase of oil generation was in the Late Palaeocene / Early to Middle Eocene and the main phase of oil generation was in the Middle to Late Eocene. The Early Barremian Shale reached the main phase of oil generation in the Early Oligocene with late generation being reached in the Middle Miocene. For the Rakb Group section (Rachmat Formation, Tagrifet Limestone and Sirt Shale Formation) the early phase of oil generation started in the Late Eocene with the main phase of generation being between the Early Oligocene and the Early Miocene. From studying maturity profiles and from regional considerations it can be predicted that up to 500’ of sediment may have been deposited and eroded by the Sirt Unconformity in the central Maragh Low while up to 2000’ of sediment may have been deposited and then eroded to the south of the trough.

Keywords: Geochemical analysis of the source rocks from wells in Eastern Sirt Basin.

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63 Carthage-Burned and Rome-Reiterative: Mirrored Distortions of Imperial Trauma and Historiography

Authors: Sarah H. Davies

Abstract:

In the year 146 BCE, the Roman general Scipio Aemilianus – soon to be ‘anointed,’ via mass-spilling of blood-on-land, as “(‘triumphal’) Africanus” – stood atop a hill, overlooking the city of Carthage, as its urban-scape was burned and people killed, violated, captured… ‘poetically’ consumed. From an ineffable-seeming distance – constructed, in imperial fascination – the scene was (and is, apparently) painted in a disturbingly ‘romantic’ light. Such a snap-shot vista, projected before a mind’s-eye in panorama, and in (ongoing) construction, has seeped across ancient and modern lines, with multiple, interwoven iterations. This study conducts a reading, both ‘postcolonial’ and anti-imperial, in interruption of an ongoing (re)iteration of imperial violence, mirrored in distortion between “ancient” and “modern” forms that are physical, ideological, and ontological. Using an analysis of ancient literary works, from the historiographical (Polybius’ Histories) to the epic-poetic (Vergil’s Aeneid), placed in juxtaposition with a range of modern material, both literary-historical (e.g., Gibbon’s Decline & Fall of the Roman Empire) and visual (Cole’s The Course of Empire), this study destabilizes ongoing formations. Such formations attempt to inflict ‘an assumed’ repetition, engaged in normalizing a city violently destroyed as somehow ‘natural’ and/or ‘inevitable,’ and by extension, ‘tragically necessary.’ The reiterations – across media and contexts – create a distorted aesthetic (itself an act of profound violence) that fetishizes and even produces sensory, illusory pleasures (of co-complicit harm, within and across communities) regarding ‘period-shifting events’ of mass-murder and cultural erasure. ‘The vista over Carthage burning’ was/is (but does not ever have to be) thereby a manufactured stage-set, a commodity for imperial reproduction. Such a projection frames an overly-simplistic, ‘safe’-seeming (and yet incredibly dangerous) binary regarding (caricatured) “victims” and “victors.” At the same time, the projection renders an epistemological frame whereby ‘The One’ and ‘The Other’ are asserted as inherently antagonistic categories of being, in which One ‘must’ replace Other – the latter portrayed in gendered, exoticized, and time-distorted ways, as a scripted-object. All the while, a very particular subset of narrative is woven, whereby Carthage (elided in ‘victim’ status) specifically is/was Troy (again, elided), is/was every ‘destroyed city’ (also elided), and is/was yet another essential marking-point of “History,” twisted into ‘becoming’ a ‘reset’ point in a ‘cyclical pattern,’ inscribed as a tragic plot or lifetime repeated. The script itself entails pervasive violence. And yet, there always remains a trip-wire written into the constructed-cyclical. In part, this realization comes from a deconstruction of the tiered violences of an over-worn trope. The realization then also comes from a revelation of erased realities of human-experiences, in which ‘victim’ and ‘victor’ suffer, in fractured differences of ongoing, system(at)ic (re)trauma. The contours and silences of the historical records contain all the ongoing scars. This study therefore unravels the intersectional tableaux of ‘Carthage-burning’ and ‘Rome-reiterative,’ providing a collective investigation into conceptual formations, fractured across millennia. Ultimately, perhaps, such a re-reading – occurring via a commodified past will echo words from the Aeneid: “perhaps, once upon a time, to have remembered even these things, it will have been healing.

Keywords: antiquity, carthage, empire, historiography, rome, ruination

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62 Effect of Additives on Post-hydrogen Decompression Microstructure and Mechanical Behaviour of PA11 Involved in Type-IV Hydrogen Tank Liners

Authors: Mitia Ramarosaona, Sylvie Castagnet, Damien Halm, Henri-Alexandre Cayzac, Nicolas Dufaure, Philippe Papin

Abstract:

In light of the ongoing energy transition, 'Infrastructure developments' for hydrogen transportation and storage raise studies on the materials employed for hyperbaric vessels. Type IV tanks represent the most mature choice for gaseous hydrogen storage at high pressure – 70MPa. These tanks are made of a composite shell and an internal hydrogen-exposed polymer liner. High pressure conditions lead to severe mechanical loading requiring high resistance. Liner is in contact with hydrogen and undergoes compression – decompression cycles during system filling and emptying. Stresses induced by this loading, coupled with hydrogen diffusion, were found to cause microstructural changes and degradation of mechanical behaviour after decompression phase in some studies on HDPE. These phenomena are similar to those observed in elastomeric components like sealing rings, which can affect permeability and lead to their failure. They may lead to a hydrogen leak, compromising security and tightness of the tank. While these phenomena have been identified in elastomers, they remain less addressed in thermoplastics and consequences post-decompression damages on mechanical behaviour and to the best of author's knowledge was not studied either. Different additives are also included in liner formulation to improve its behaviour. This study aimed to better understand damage micro-mechanisms in PA11s exposed to hydrogen compression-decompression cycles and understand if additives influence their resistance. Samples of pure, plasticized and impact-modified PA11s are exposed to 1, 3 and 8 pressure cycles including hydrogen saturation at 70MPa followed by severe 15-second decompression. After hydrogen exposure and significantly later than full desorption, the residual mechanical behaviour is characterized through impact and monotonic tensile tests, on plain and notched samples. Several techniques of microstructure and micro-nano damage characterization are carried out to assess whether changes in macroscopic properties are driven by microstructural changes in the crystalline structure (SAXS-WAXS acquisitions and SEM micrographs). Thanks to WAXS acquisition and microscopic observation, the effects due to additives and pressure consequences can be decorrelated. Pure PA11 and PA11 with a low percentage of additives show an increase in stress level at the first yielding point after hydrogen cycles. The amplitude of the stress increase is more important in formulation with additives because of changes in PA11 matrix behavior and environment created by additives actions. Plasticizer modifies chain mobility leading to microstructure changes while other additives, more ductile than PA11, is able to cavitate inside PA11 matrix when undergoing decompression. On plasticized formulation, plasticizer migration are suspected to enhance impact of hydrogen cycling on mechanical behaviour. Compared to the literature on HDPE and elastomers, no damages like cavitation or cracking could be evidenced from SAXS experiments on every PA11 formulation tested. In perspectives, on all formulation, experimental work is underway to confirm influence of residual pressure level after decompression on post-decompression damages level, the aim is to better understand the factors affecting the mechanical behavior of thermoplastics subject to mechanical solicitation from decompression in hydrogen tank liners, not mechanical behaviour of liner in hydrogen tanks directly.

Keywords: additives, hydrogen tank liner, microstructural analysis, PA11

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61 Current Zonal Isolation Regulation and Standards: A Compare and Contrast Review in Plug and Abandonment

Authors: Z. A. Al Marhoon, H. S. Al Ramis, C. Teodoriu

Abstract:

Well-integrity is one of the major elements considered for drilling geothermal, oil, and gas wells. Well-integrity is minimizing the risk of unplanned fluid flow in the well bore throughout the well lifetime. Well integrity is maximized by applying technical concepts along with practical practices and strategic planning. These practices are usually governed by standardization and regulation entities. Practices during well construction can affect the integrity of the seal at the time of abandonment. On the other hand, achieving a perfect barrier system is impracticable due to the needed cost. This results in a needed balance between regulations requirements and practical applications. The guidelines are only effective when they are attainable in practical applications. Various governmental regulations and international standards have different guidelines on what constitutes high-quality isolation from unwanted flow. Each regulating or standardization body differ in requirements based on the abandonment objective. Some regulation account more for the environmental impact, water table contamination, and possible leaks. Other regulation might lean towards driving more economical benefits while achieving an acceptable isolation criteria. The research methodology used in this topic is derived from a literature review method combined with a compare and contrast analysis. The literature review on various zonal isolation regulations and standards has been conducted. A review includes guidelines from NORSOK (Norwegian governing entity), BSEE (USA offshore governing entity), API (American Petroleum Institute) combined with ISO (International Standardization Organization). The compare and contrast analysis is conducted by assessing the objective of each abandonment regulations and standardization. The current state of well barrier regulation is in balancing action. From one side of this balance, the environmental impact and complete zonal isolation is considered. The other side of the scale is practical application and associated cost. Some standards provide a fair amount of details concerning technical requirements and are often flexible with the needed associated cost. These guidelines cover environmental impact with laws that prevent major or disastrous environmental effects of improper sealing of wells. Usually these regulations are concerned with the near future of sealing rather than long-term. Consequently, applying these guidelines become more feasible from a cost point of view to the required plugging entities. On the other hand, other regulation have well integrity procedures and regulations that lean toward more restrictions environmentally with an increased associated cost requirements. The environmental impact is detailed and covered with its entirety, including medium to small environmental impact in barrier installing operations. Clear and precise attention to long-term leakage prevention is present in these regulations. The result of the compare and contrast analysis of the literature showed that there are various objectives that might tip the scale from one side of the balance (cost) to the other (sealing quality) especially in reference to zonal isolation. Furthermore, investing in initial well construction is a crucial part of ensuring safe final well abandonment. The safety and the cost saving at the end of the well life cycle is dependent upon a well-constructed isolation systems at the beginning of the life cycle. Long term studies on zonal isolation using various hydraulic or mechanical materials need to take place to further assess permanently abandoned wells to achieve the desired balance. Well drilling and isolation techniques will be more effective when they are operationally feasible and have reasonable associated cost to aid the local economy.

Keywords: plug and abandon, P&A regulation, P&A standards, international guidelines, gap analysis

Procedia PDF Downloads 133
60 Sustainable Urban Regenaration the New Vocabulary and the Timless Grammar of the Urban Tissue

Authors: Ruth Shapira

Abstract:

Introduction: The rapid urbanization of the last century confronts planners, regulatory bodies, developers and most of all the public with seemingly unsolved conflicts regarding values, capital, and wellbeing of the built and un-built urban space. There is an out of control change of scale of the urban form and of the rhythm of the urban life which has known no significant progress in the last 2-3 decades despite the on-growing urban population. It is the objective of this paper to analyze some of these fundamental issues through the case study of a relatively small town in the center of Israel (Kiryat-Ono, 36,000 inhabitants), unfold the deep structure of qualities versus disruptors, present some cure that we have developed to bridge over and humbly suggest a practice that may bring about a sustainable new urban environment based on timeless values of the past, an approach that can be generic for similar cases. Basic Methodologies:The object, the town of Kiryat Ono, shall be experimented upon in a series of four action processes: De-composition, Re-composition, the Centering process and, finally, Controlled Structural Disintegration. Each stage will be based on facts, analysis of previous multidisciplinary interventions on various layers – and the inevitable reaction of the OBJECT, leading to the conclusion based on innovative theoretical and practical methods that we have developed and that we believe are proper for the open ended network, setting the rules for the contemporary urban society to cluster by – thus – a new urban vocabulary based on the old structure of times passed. The Study: Kiryat Ono, was founded 70 years ago as an agricultural settlement and rapidly turned into an urban entity. In spite the massive intensification, the original DNA of the old small town was still deeply embedded, mostly in the quality of the public space and in the sense of clustered communities. In the past 20 years, the recent demand for housing has been addressed to on the national level with recent master plans and urban regeneration policies mostly encouraging individual economic initiatives. Unfortunately, due to the obsolete existing planning platform the present urban renewal is characterized by pressure of developers, a dramatic change in building scale and widespread disintegration of the existing urban and social tissue.Our office was commissioned to conceptualize two master plans for the two contradictory processes of Kiryat Ono’s future: intensification and conservation. Following a comprehensive investigation into the deep structures and qualities of the existing town, we developed a new vocabulary of conservation terms thus redefying the sense of PLACE. The main challenge was to create master plans that should offer a regulatory basis to the accelerated and sporadic development providing for the public good and preserving the characteristics of the place consisting of a tool box of design guidelines that will have the ability to reorganize space along the time axis in a sustainable way. In conclusion: The system of rules that we have developed can generate endless possible patterns making sure that at each implementation fragment an event is created, and a better place is revealed. It takes time and perseverance but it seems to be the way to provide a healthy and sustainable framework for the accelerated urbanization of our chaotic present.

Keywords: sustainable urban design, intensification, emergent urban patterns, sustainable housing, compact urban neighborhoods, sustainable regeneration, restoration, complexity, uncertainty, need for change, implications of legislation on local planning

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59 Facies Analysis and Depositional Environment of the Late Carboniferous (Stephanian) Souss Basin, Morocco

Authors: Abouchouaib Belahmira, Joerg W. Schneider, Hafid Saber, Sara Akboub

Abstract:

The lithofacies analyzed herein were reported from the interbedded fluvial and lacustrine deposits of the Oued Issene and El Menizla formations. These formations are part of the sedimentary fill of the Carboniferous (Stephanian) submontaneous Souss basin. The latter is situated in the western High Atlas Mountains, south-central Morocco, about 50km east of Agadir. The Souss basin started as a single basin but was separated into sub-basins called Ida Ou Zal and Ida Ou Ziki by sinistral displacement along the west branch of the Tizi N'Test Fault during the end of the Mauritanid phase of the Variscan orogeny in Morocco, after the early Stephanian (Kasimovian) and before the late middle Permian (Capitanian). The studied succession is a monotonous finning-upward sequence of 1800 m thick. It consists of fine-grained sandstone, finely bedded siltstone and thinly laminated claystone, and black shale. Herein we provide a detailed characterization of lithofacies of the upper El Menizla and Oued Issène formations, with a focus on the prevailing overbank to flood plain fine-grained lithofacies. The studied facies are capping the Stephanian alluvial fan basal clast-supported conglomerates that are intercalated bedded coarse-grained sandstones of Ikhourba Formation in the Ou Zal subbasin and Tajgaline Formation in the Ida Ou Ziki subbasin, respectively. Within the fluvial elements, only two main facies have been observed. It comprises channel-fill and channel-bar deposits, mostly occur as lenticular –shape sand bodies or sheet-like sand greenish to gray fine-to medium (Fm), massive internally structureless, or very locally exhibits a medium to large scale trough-cross bedding medium to coarse sandstone (St), observable in relatively thicker bed. These facies are laterally extensive, with a thickness varying from a few to several meters. Finer-grained sediments such as mud can be present as drapes over bedforms. Whilst the fluvial association FA1, the overbank elements are represented by a relatively wide range of 5 facies. This exhibit mostly a cm scale horizontally bedded greenish fine- to medium sand and silt, and mm scale fossiliferous thinly laminated dark gray- black Corganic-rich clays to siltstone associated with black shale. Thus, FA2 includes flood plain fines (Fh, R) associated with the paleosols and back swamp coaly clay facies (C). The floodplain lake element comprises only laminated organic-rich dark gray facies of claystone, black shale, and graded siltstone. Bedsets are dm to several meters thick (typically < 1 m thick). They are intercalated between several m-thick fluvial sandstone, extend over a few meters, and are poorly bioturbated. The lacustrine facies described in this study have been divided into two sub-facies (Fl, B) based on field observations that indicate differing environmental conditions of formation. Thus, the thorough analysis of the lithofacies of the Souss basin units allows us to reconstruct the original environment that was interpreted as a typical fluvial-dominated braided to anastomosing wide distributary channel system and surrounding deep to shallow freshwater floodplain lakes and back swamps.

Keywords: Souss, carboniferous, facies, depositional setting

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58 Phenotype and Psychometric Characterization of Phelan-Mcdermid Syndrome Patients

Authors: C. Bel, J. Nevado, F. Ciceri, M. Ropacki, T. Hoffmann, P. Lapunzina, C. Buesa

Abstract:

Background: The Phelan-McDermid syndrome (PMS) is a genetic disorder caused by the deletion of the terminal region of chromosome 22 or mutation of the SHANK3 gene. Shank3 disruption in mice leads to dysfunction of synaptic transmission, which can be restored by epigenetic regulation with both Lysine Specific Demethylase 1 (LSD1) inhibitors. PMS subjects result in a variable degree of intellectual disability, delay or absence of speech, autistic spectrum disorders symptoms, low muscle tone, motor delays and epilepsy. Vafidemstat is an LSD1 inhibitor in Phase II clinical development with a well-established and favorable safety profile, and data supporting the restoration of memory and cognition defects as well as reduction of agitation and aggression in several animal models and clinical studies. Therefore, vafidemstat has the potential to become a first-in-class precision medicine approach to treat PMS patients. Aims: The goal of this research is to perform an observational trial to psychometrically characterize individuals carrying deletions in SHANK3 and build a foundation for subsequent precision psychiatry clinical trials with vafidemstat. Methodology: This study is characterizing the clinical profile of 20 to 40 subjects, > 16-year-old, with genotypically confirmed PMS diagnosis. Subjects will complete a battery of neuropsychological scales, including the Repetitive Behavior Questionnaire (RBQ), Vineland Adaptive Behavior Scales, Escala de Observación para el Diagnostico del Autismo (Autism Diagnostic Observational Scale) (ADOS)-2, the Battelle Developmental Inventory and the Behavior Problems Inventory (BPI). Results: By March 2021, 19 patients have been enrolled. Unsupervised hierarchical clustering of the results obtained so far identifies 3 groups of patients, characterized by different profiles of cognitive and behavioral scores. The first cluster is characterized by low Battelle age, high ADOS and low Vineland, RBQ and BPI scores. Low Vineland, RBQ and BPI scores are also detected in the second cluster, which in contrast has high Battelle age and low ADOS scores. The third cluster is somewhat in the middle for the Battelle, Vineland and ADOS scores while displaying the highest levels of aggression (high BPI) and repeated behaviors (high RBQ). In line with the observation that female patients are generally affected by milder forms of autistic symptoms, no male patients are present in the second cluster. Dividing the results by gender highlights that male patients in the third cluster are characterized by a higher frequency of aggression, whereas female patients from the same cluster display a tendency toward higher repetitive behavior. Finally, statistically significant differences in deletion sizes are detected comparing the three clusters (also after correcting for gender), and deletion size appears to be positively correlated with ADOS and negatively correlated with Vineland A and C scores. No correlation is detected between deletion size and the BPI and RBQ scores. Conclusions: Precision medicine may open a new way to understand and treat Central Nervous System disorders. Epigenetic dysregulation has been proposed to be an important mechanism in the pathogenesis of schizophrenia and autism. Vafidemstat holds exciting therapeutic potential in PMS, and this study will provide data regarding the optimal endpoints for a future clinical study to explore vafidemstat ability to treat shank3-associated psychiatric disorders.

Keywords: autism, epigenetics, LSD1, personalized medicine

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57 TeleEmergency Medicine: Transforming Acute Care through Virtual Technology

Authors: Ashley L. Freeman, Jessica D. Watkins

Abstract:

TeleEmergency Medicine (TeleEM) is an innovative approach leveraging virtual technology to deliver specialized emergency medical care across diverse healthcare settings, including internal acute care and critical access hospitals, remote patient monitoring, and nurse triage escalation, in addition to external emergency departments, skilled nursing facilities, and community health centers. TeleEM represents a significant advancement in the delivery of emergency medical care, providing healthcare professionals the capability to deliver expertise that closely mirrors in-person emergency medicine, exceeding geographical boundaries. Through qualitative research, the extension of timely, high-quality care has proven to address the critical needs of patients in remote and underserved areas. TeleEM’s service design allows for the expansion of existing services and the establishment of new ones in diverse geographic locations. This ensures that healthcare institutions can readily scale and adapt services to evolving community requirements by leveraging on-demand (non-scheduled) telemedicine visits through the deployment of multiple video solutions. In terms of financial management, TeleEM currently employs billing suppression and subscription models to enhance accessibility for a wide range of healthcare facilities. Plans are in motion to transition to a billing system routing charges through a third-party vendor, further enhancing financial management flexibility. To address state licensure concerns, a patient location verification process has been integrated through legal counsel and compliance authorities' guidance. The TeleEM workflow is designed to terminate if the patient is not physically located within licensed regions at the time of the virtual connection, alleviating legal uncertainties. A distinctive and pivotal feature of TeleEM is the introduction of the TeleEmergency Medicine Care Team Assistant (TeleCTA) role. TeleCTAs collaborate closely with TeleEM Physicians, leading to enhanced service activation, streamlined coordination, and workflow and data efficiencies. In the last year, more than 800 TeleEM sessions have been conducted, of which 680 were initiated by internal acute care and critical access hospitals, as evidenced by quantitative research. Without this service, many of these cases would have necessitated patient transfers. Barriers to success were examined through thorough medical record review and data analysis, which identified inaccuracies in documentation leading to activation delays, limitations in billing capabilities, and data distortion, as well as the intricacies of managing varying workflows and device setups. TeleEM represents a transformative advancement in emergency medical care that nurtures collaboration and innovation. Not only has advanced the delivery of emergency medicine care virtual technology through focus group participation with key stakeholders, rigorous attention to legal and financial considerations, and the implementation of robust documentation tools and the TeleCTA role, but it’s also set the stage for overcoming geographic limitations. TeleEM assumes a notable position in the field of telemedicine by enhancing patient outcomes and expanding access to emergency medical care while mitigating licensure risks and ensuring compliant billing.

Keywords: emergency medicine, TeleEM, rural healthcare, telemedicine

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56 Modern Technology for Strengthening Concrete Structures Makes Them Resistant to Earthquakes

Authors: Mohsen Abdelrazek Khorshid Ali Selim

Abstract:

Disadvantages and errors of current concrete reinforcement methodsL: Current concrete reinforcement methods are adopted in most parts of the world in their various doctrines and names. They adopt the so-called concrete slab system, where these slabs are semi-independent and isolated from each other and from the surrounding environment of concrete columns or beams, so that the reinforcing steel does not cross from one slab to another or from one slab to adjacent columns. It or the beams surrounding it and vice versa are only a few centimeters and no more. The same applies exactly to the concrete columns that support the building, where the reinforcing steel does not extend from the slabs or beams to the inside of the columns or vice versa except for a few centimeters and no more, just as the reinforcing steel does not extend from inside the column at the top. The ceiling is only a few centimetres, and the same thing is literally repeated in the concrete beams that connect the columns and separate the slabs, where the reinforcing steel does not cross from one beam to another or from one beam to the slabs or columns adjacent to it and vice versa, except for a few centimeters, which makes the basic building elements of columns, slabs and beams They all work in isolation from each other and from the environment surrounding them from all sides. This traditional method of reinforcement may be valid and lasting in geographical areas that are not exposed to earthquakes and earthquakes, where all the loads and tensile forces in the building are constantly directed vertically downward due to gravity and are borne directly by the vertical reinforcement of the building. However, in the case of earthquakes and earthquakes, the loads and tensile forces in the building shift from the vertical direction to the horizontal direction at an angle of inclination that depends on the strength of the earthquake, and most of them are borne by the horizontal reinforcement extending between the basic elements of the building, such as columns, slabs and beams, and since the crossing of the reinforcement between each of the columns, slabs and beams between them And each other, and vice versa, does not exceed several centimeters. In any case, the tensile strength, cohesion and bonding between the various parts of the building are very weak, which causes the buildings to disintegrate and collapse in the horrific manner that we saw in the earthquake in Turkey and Syria in February 2023, which caused the collapse of tens of thousands of buildings in A few seconds later, it left more than 50,000 dead, hundreds of thousands injured, and millions displaced. Description of the new earthquake-resistant model: The idea of the new model in the reinforcement of concrete buildings and constructions is based on the theory that we have formulated as follows: [The tensile strength, cohesion and bonding between the basic parts of the concrete building (columns, beams and slabs) increases as the lengths of the reinforcing steel bars increase and they extend and branch and the different parts of the building share them with each other.] . In other words, the strength, solidity, and cohesion of concrete buildings increase and they become resistant to earthquakes as the lengths of the reinforcing steel bars increase, extend, branch, and share with the various parts of the building, such as columns, beams, and slabs. That is, the reinforcing skewers of the columns must extend in their lengths without cutting to cross from one floor to another until their end. Likewise, the reinforcing skewers of the beams must extend in their lengths without cutting to cross from one beam to another. The ends of these skewers must rest at the bottom of the columns adjacent to the beams. The same thing applies to the reinforcing skewers of the slabs where they must These skewers should be extended in their lengths without cutting to cross from one tile to another, and the ends of these skewers should rest either under the adjacent columns or inside the beams adjacent to the slabs as follows: First, reinforce the columns: The columns have the lion's share of the reinforcing steel in this model in terms of type and quantity, as the columns contain two types of reinforcing bars. The first type is large-diameter bars that emerge from the base of the building, which are the nerves of the column. These bars must extend over their normal length of 12 meters or more and extend to a height of three floors, if desired. In raising other floors, bars with the same diameter and the same length are added to the top after the second floor. The second type is bars with a smaller diameter, and they are the same ones that are used to reinforce beams and slabs, so that the bars that reinforce the beams and slabs facing each column are bent down inside this column and along the entire length of the column. This requires an order. Most engineers do not prefer it, which is to pour the entire columns and pour the roof at once, but we prefer this method because it enables us to extend the reinforcing bars of both the beams and slabs to the bottom of the columns so that the entire building becomes one concrete block that is cohesive and resistant to earthquakes. Secondly, arming the cameras: The beams' reinforcing skewers must also extend to a full length of 12 meters or more without cutting. The ends of the skewers are bent and dropped inside the column at the beginning of the beam to its bottom. Then the skewers are extended inside the beam so that their other end falls under the facing column at the end of the beam. The skewers may cross over the head of a column. Another passes through another adjacent beam and rests at the bottom of a third column, according to the lengths of each of the skewers and beams. Third, reinforcement of slabs: The slab reinforcing skewers must also extend their entire length, 12 meters or more, without cutting, distinguishing between two cases. The first case is the skewers opposite the columns, and their ends are dropped inside one of the columns. Then the skewers cross inside the adjacent slab and their other end falls below the opposite column. The skewers may cross over The head of the adjacent column passes through another adjacent slab and rests at the bottom of a third column, according to the dimensions of the slabs and the lengths of the skewers. The second case is the skewers opposite the beams, and their ends must be bent in the form of a square or rectangle according to the dimensions of the beam’s width and height, and this square or rectangle is dropped inside the beam at the beginning of the slab, and it serves as The skewers are for the beams, then the skewers are extended along the length of the slab, and at the end of the slab, the skewers are bent down to the bottom of the adjacent beam in the shape of the letter U, after which the skewers are extended inside the adjacent slab, and this is repeated in the same way inside the other adjacent beams until the end of the skewer, then it is bent downward in the form of a square or rectangle inside the beam, as happened. In its beginning.

Keywords: earthquake resistant buildings, earthquake resistant concrete constructions, new technology for reinforcement of concrete buildings, new technology in concrete reinforcement

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55 A Lightning Strike Mimic: The Abusive Use of Dog Shock Collar Presents as Encephalopathy, Respiratory Arrest, Cardiogenic Shock, Severe Hypernatremia, Rhabdomyolysis, and Multiorgan Injury

Authors: Merrick Lopez, Aashish Abraham, Melissa Egge, Marissa Hood, Jui Shah

Abstract:

A 3 year old male with unknown medical history presented initially with encephalopathy, intubated for respiratory failure, and admitted to the pediatric intensive care unit (PICU) with refractory shock. During resuscitation in the emergency department, he was found to be in severe metabolic acidosis with a pH of 7.03 and escalated on vasopressor drips for hypotension. His initial sodium was 174. He was noted to have burn injuries to his scalp, forehead, right axilla, bilateral arm creases and lower legs. He had rhabdomyolysis (initial creatinine kinase 5,430 U/L with peak levels of 62,340 normal <335 U/L), cardiac injury (initial troponin 88 ng/L with peak at 145 ng/L, normal <15ng/L), hypernatremia (peak 174, normal 140), hypocalcemia, liver injury, acute kidney injury, and neuronal loss on magnetic resonance imaging (MRI). Soft restraints and a shock collar were found in the home. He was critically ill for 8 days, but was gradually weaned off drips, extubated, and started on feeds. Discussion Electrical injury, specifically lightning injury is an uncommon but devastating cause of injury in pediatric patients. This patient with suspected abusive use of a dog shock collar presented similar to a lightning strike. Common entrance points include the hands and head, similar to our patient with linear wounds on his forehead. When current enters, it passes through tissues with the least resistance. Nerves, blood vessels, and muscles, have high fluid and electrolyte content and are commonly affected. Exit points are extremities: our child who had circumferential burns around his arm creases and ankles. Linear burns preferentially follow areas of high sweat concentration, and are thought to be due to vaporization of water on the skin’s surface. The most common cause of death from a lightning strike is due to cardiopulmonary arrest. The massive depolarization of the myocardium can result in arrhythmias and myocardial necrosis. The patient presented in cardiogenic shock with evident cardiac damage. Electricity going through vessels can lead to vaporization of intravascular water. This can explain his severe hypernatremia. He also sustained other internal organ injuries (adrenal glands, pancreas, liver, and kidney). Electrical discharge also leads to direct skeletal muscle injury in addition to prolonged muscular spasm. Rhabdomyolysis, the acute damage of muscle, leads to release of potentially toxic components into the circulation which could lead to acute renal failure. The patient had severe rhabdomyolysis and renal injury. Early hypocalcemia has been consistently demonstrated in patients with rhabdomyolysis. This was present in the patient and led to increased vasopressor needs. Central nervous system injuries are also common which can include encephalopathy, hypoxic injury, and cerebral infarction. The patient had evidence of brain injury as seen on MRI. Conclusion Electrical injuries due to lightning strikes and abusive use of a dog shock collar are rare, but can both present in similar ways with respiratory failure, shock, hypernatremia, rhabdomyolysis, brain injury, and multiorgan damage. Although rare, it is essential for early identification and prompt management for acute and chronic complications in these children.

Keywords: cardiogenic shock, dog shock collar, lightning strike, rhabdomyolysis

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54 Multiple Primary Pulmonary Meningiomas: A Case Report

Authors: Wellemans Isabelle, Remmelink Myriam, Foucart Annick, Rusu Stefan, Compère Christophe

Abstract:

Primary pulmonary meningioma (PPM) is a very rare tumor, and its occurrence has been reported only sporadically. Multiple PPMs are even more exceptional, and herein, we report, to the best of our knowledge, the fourth case, focusing on the clinicopathological features of the tumor. Moreover, the possible relationship between the use of progesterone–only contraceptives and the development of these neoplasms will be discussed. Case Report: We report a case of a 51-year-old female presenting three solid pulmonary nodules, with the following localizations: right upper lobe, middle lobe, and left lower lobe, described as incidental findings on computed tomography (CT) during a pre-bariatric surgery check-up. The patient revealed no drinking or smoking history. The physical exam was unremarkable except for the obesity. The lesions ranged in size between 6 and 24 mm and presented as solid nodules with lobulated contours. The largest lesion situated in the middle lobe had mild fluorodeoxyglucose (FDG) uptake on F-18 FDG positron emission tomography (PET)/CT, highly suggestive of primary lung neoplasm. For pathological assessment, video-assisted thoracoscopic middle lobectomy and wedge resection of the right upper nodule was performed. Histological examination revealed relatively well-circumscribed solid proliferation of bland meningothelial cells growing in whorls and lobular nests, presenting intranuclear pseudo-inclusions and psammoma bodies. No signs of anaplasia were observed. The meningothelial cells expressed diffusely Vimentin, focally Progesterone receptors and were negative for epithelial (cytokeratin (CK) AE1/AE3, CK7, CK20, Epithelial Membrane Antigen (EMA)), neuroendocrine markers (Synaptophysin, Chromogranin, CD56) and Estrogenic receptors. The proliferation labelling index Ki-67 was low (<5%). Metastatic meningioma was ruled out by brain and spine magnetic resonance imaging (MRI) scans. The third lesion localized in the left lower lobe was followed-up and resected three years later because of its slow but significant growth (14 mm to 16 mm), alongside two new infra centimetric lesions. Those three lesions showed a morphological and immunohistochemical profile similar to previously resected lesions. The patient was disease-free one year post-last surgery. Discussion: Although PPMs are mostly benign and slow-growing tumors with an excellent prognosis, they do not present specific radiological characteristics, and it is difficult to differentiate it from other lung tumors, histopathologic examination being essential. Aggressive behavior is associated with atypical or anaplastic features (WHO grades II–III) The etiology is still uncertain and different mechanisms have been proposed. A causal connection between sexual hormones and meningothelial proliferation has long been suspected and few studies examining progesterone only contraception and meningioma risk have all suggested an association. In line with this, our patient was treated with Levonorgestrel, a progesterone agonist, intra-uterine device (IUD). Conclusions: PPM, defined by the typical histological and immunohistochemical features of meningioma in the lungs and the absence of central nervous system lesions, is an extremely rare neoplasm, mainly solitary and associating, and indolent growth. Because of the unspecific radiologic findings, it should always be considered in the differential diagnosis of lung neoplasms. Regarding multiple PPM, only three cases are reported in the literature, and this is the first described in a woman treated by a progesterone-only IUD to the best of our knowledge.

Keywords: pulmonary meningioma, multiple meningioma, meningioma, pulmonary nodules

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53 Successful Public-Private Partnership Through the Impact of Environmental Education: A Case Study on Transforming Community Confrict into Harmony in the Dongpian Community

Authors: Men An Pan, Ho Hsiung Huang, Jui Chuan Lin, Tsui Hsun Wu, Hsing Yuan Yen

Abstract:

Pingtung County, located in the southernmost region of Taiwan, has the largest number of pig farms in the country. In the past, livestock operators in Dongpian Village discharged their wastewater into the nearby water bodies, causing water pollution in the local rivers and polluting the air with the stench of the pig excrement. These resulted in many complaints from the local residents. In response to a long time fighting back of the community against the livestock farms due to the confrict, the County Government's Environmental Protection Bureau (PTEPB) examined potential wayouts in addition to heavy fines to the perpetrators. Through helping the livestock farms to upgrade their pollution prevention equipment, promoting the reuse of biogas residue and slurry from the pig excrement, and environmental education, the confrict was successfully resolved. The properly treated wastewater from the livestock farms has been freely provided to the neighboring farmlands via pipelines and tankers. Thus, extensive cultivation of bananas, papaya, red dragon fruit, Inca nut, and cocoa has resulted in 34% resource utilization of biogas residue as a fertilizer. This has encouraged farmers to reduce chemical fertilizers and use microbial materials like photosynthetic bacteria after banning herbicides while lowering the cost of wastewater treatment in livestock farms and alleviating environmental pollution simultaneously. That is, the livestock farms fully demonstrate the determination to fulfill their corporate social responsibility (CSR). Due to the success, Eight farms jointly established a social enterprise - "Dongpian Gemstone Village Co., Ltd." to promote organic farming through a "shared farm." The company appropriates 5% of its total revenue back to the community through caregiving services for the elderly and a fund for young local farmers. The community adopted the Satoyama Initiative in accordance with the Conference of the CBD COP10. Through the positive impact of environmental education, the community seeks to realize the coexistence between society and nature while maintaining and developing socio-economic activities (including agriculture) with respect for nature and building a harmonic relationship between humans and nature. By way of sustainable management of resources and ensuring biodiversity, the community is transforming into a socio-ecological production landscape. Apart from nature conservation and watercourse ecology, preserving local culture is also a key focus of the environmental education. To mitigate the impact of global warming and climate change, the community and the government have worked together to develop a disaster prevention and relief system, strive to establish a low-carbon emitting homeland, and become a model for resilient communities. By the power of environmental education, this community has turned its residents’ hearts and minds into concrete action, fulfilled social responsibility, and moved towards realizing the UN SDGs. Even though it is not the only community to integrate government agencies, research institutions, and NGOs for environmental education, it is a prime example of a low-carbon sustainable community that achieves more than 9 SDGs, including responsible consumption and production, climate change action, and diverse partnerships. The community is also leveraging environmental education to become a net-zero carbon community targeted by COP26.

Keywords: environmental education, biogas residue, biogas slurry, CSR, SDGs, climate change, net-zero carbon emissions

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52 Analysis Of Fine Motor Skills in Chronic Neurodegenerative Models of Huntington’s Disease and Amyotrophic Lateral Sclerosis

Authors: T. Heikkinen, J. Oksman, T. Bragge, A. Nurmi, O. Kontkanen, T. Ahtoniemi

Abstract:

Motor impairment is an inherent phenotypic feature of several chronic neurodegenerative diseases, and pharmacological therapies aimed to counterbalance the motor disability have a great market potential. Animal models of chronic neurodegenerative diseases display a number deteriorating motor phenotype during the disease progression. There is a wide array of behavioral tools to evaluate motor functions in rodents. However, currently existing methods to study motor functions in rodents are often limited to evaluate gross motor functions only at advanced stages of the disease phenotype. The most commonly applied traditional motor assays used in CNS rodent models, lack the sensitivity to capture fine motor impairments or improvements. Fine motor skill characterization in rodents provides a more sensitive tool to capture more subtle motor dysfunctions and therapeutic effects. Importantly, similar approach, kinematic movement analysis, is also used in clinic, and applied both in diagnosis and determination of therapeutic response to pharmacological interventions. The aim of this study was to apply kinematic gait analysis, a novel and automated high precision movement analysis system, to characterize phenotypic deficits in three different chronic neurodegenerative animal models, a transgenic mouse model (SOD1 G93A) for amyotrophic lateral sclerosis (ALS), and R6/2 and Q175KI mouse models for Huntington’s disease (HD). The readouts from walking behavior included gait properties with kinematic data, and body movement trajectories including analysis of various points of interest such as movement and position of landmarks in the torso, tail and joints. Mice (transgenic and wild-type) from each model were analyzed for the fine motor kinematic properties at young ages, prior to the age when gross motor deficits are clearly pronounced. Fine motor kinematic Evaluation was continued in the same animals until clear motor dysfunction with conventional motor assays was evident. Time course analysis revealed clear fine motor skill impairments in each transgenic model earlier than what is seen with conventional gross motor tests. Motor changes were quantitatively analyzed for up to ~80 parameters, and the largest data sets of HD models were further processed with principal component analysis (PCA) to transform the pool of individual parameters into a smaller and focused set of mutually uncorrelated gait parameters showing strong genotype difference. Kinematic fine motor analysis of transgenic animal models described in this presentation show that this method isa sensitive, objective and fully automated tool that allows earlier and more sensitive detection of progressive neuromuscular and CNS disease phenotypes. As a result of the analysis a comprehensive set of fine motor parameters for each model is created, and these parameters provide better understanding of the disease progression and enhanced sensitivity of this assay for therapeutic testing compared to classical motor behavior tests. In SOD1 G93A, R6/2, and Q175KI mice, the alterations in gait were evident already several weeks earlier than with traditional gross motor assays. Kinematic testing can be applied to a wider set of motor readouts beyond gait in order to study whole body movement patterns such as with relation to joints and various body parts longitudinally, providing a sophisticated and translatable method for disseminating motor components in rodent disease models and evaluating therapeutic interventions.

Keywords: Gait analysis, kinematic, motor impairment, inherent feature

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51 Surface Sunctionalization Strategies for the Design of Thermoplastic Microfluidic Devices for New Analytical Diagnostics

Authors: Camille Perréard, Yoann Ladner, Fanny D'Orlyé, Stéphanie Descroix, Vélan Taniga, Anne Varenne, Cédric Guyon, Michael. Tatoulian, Frédéric Kanoufi, Cyrine Slim, Sophie Griveau, Fethi Bedioui

Abstract:

The development of micro total analysis systems is of major interest for contaminant and biomarker analysis. As a lab-on-chip integrates all steps of an analysis procedure in a single device, analysis can be performed in an automated format with reduced time and cost, while maintaining performances comparable to those of conventional chromatographic systems. Moreover, these miniaturized systems are either compatible with field work or glovebox manipulations. This work is aimed at developing an analytical microsystem for trace and ultra trace quantitation in complex matrices. The strategy consists in the integration of a sample pretreatment step within the lab-on-chip by a confinement zone where selective ligands are immobilized for target extraction and preconcentration. Aptamers were chosen as selective ligands, because of their high affinity for all types of targets (from small ions to viruses and cells) and their ease of synthesis and functionalization. This integrated target extraction and concentration step will be followed in the microdevice by an electrokinetic separation step and an on-line detection. Polymers consisting of cyclic olefin copolymer (COC) or fluoropolymer (Dyneon THV) were selected as they are easy to mold, transparent in UV-visible and have high resistance towards solvents and extreme pH conditions. However, because of their low chemical reactivity, surface treatments are necessary. For the design of this miniaturized diagnostics, we aimed at modifying the microfluidic system at two scales : (1) on the entire surface of the microsystem to control the surface hydrophobicity (so as to avoid any sample wall adsorption) and the fluid flows during electrokinetic separation, or (2) locally so as to immobilize selective ligands (aptamers) on restricted areas for target extraction and preconcentration. We developed different novel strategies for the surface functionalization of COC and Dyneon, based on plasma, chemical and /or electrochemical approaches. In a first approach, a plasma-induced immobilization of brominated derivatives was performed on the entire surface. Further substitution of the bromine by an azide functional group led to covalent immobilization of ligands through “click” chemistry reaction between azides and terminal alkynes. COC and Dyneon materials were characterized at each step of the surface functionalization procedure by various complementary techniques to evaluate the quality and homogeneity of the functionalization (contact angle, XPS, ATR). With the objective of local (micrometric scale) aptamer immobilization, we developed an original electrochemical strategy on engraved Dyneon THV microchannel. Through local electrochemical carbonization followed by adsorption of azide-bearing diazonium moieties and covalent linkage of alkyne-bearing aptamers through click chemistry reaction, typical dimensions of immobilization zones reached the 50 µm range. Other functionalization strategies, such as sol-gel encapsulation of aptamers, are currently investigated and may also be suitable for the development of the analytical microdevice. The development of these functionalization strategies is the first crucial step in the design of the entire microdevice. These strategies allow the grafting of a large number of molecules for the development of new analytical tools in various domains like environment or healthcare.

Keywords: alkyne-azide click chemistry (CuAAC), electrochemical modification, microsystem, plasma bromination, surface functionalization, thermoplastic polymers

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50 Sinhala Sign Language to Grammatically Correct Sentences using NLP

Authors: Anjalika Fernando, Banuka Athuraliya

Abstract:

This paper presents a comprehensive approach for converting Sinhala Sign Language (SSL) into grammatically correct sentences using Natural Language Processing (NLP) techniques in real-time. While previous studies have explored various aspects of SSL translation, the research gap lies in the absence of grammar checking for SSL. This work aims to bridge this gap by proposing a two-stage methodology that leverages deep learning models to detect signs and translate them into coherent sentences, ensuring grammatical accuracy. The first stage of the approach involves the utilization of a Long Short-Term Memory (LSTM) deep learning model to recognize and interpret SSL signs. By training the LSTM model on a dataset of SSL gestures, it learns to accurately classify and translate these signs into textual representations. The LSTM model achieves a commendable accuracy rate of 94%, demonstrating its effectiveness in accurately recognizing and translating SSL gestures. Building upon the successful recognition and translation of SSL signs, the second stage of the methodology focuses on improving the grammatical correctness of the translated sentences. The project employs a Neural Machine Translation (NMT) architecture, consisting of an encoder and decoder with LSTM components, to enhance the syntactical structure of the generated sentences. By training the NMT model on a parallel corpus of Sinhala wrong sentences and their corresponding grammatically correct translations, it learns to generate coherent and grammatically accurate sentences. The NMT model achieves an impressive accuracy rate of 98%, affirming its capability to produce linguistically sound translations. The proposed approach offers significant contributions to the field of SSL translation and grammar correction. Addressing the critical issue of grammar checking, it enhances the usability and reliability of SSL translation systems, facilitating effective communication between hearing-impaired and non-sign language users. Furthermore, the integration of deep learning techniques, such as LSTM and NMT, ensures the accuracy and robustness of the translation process. This research holds great potential for practical applications, including educational platforms, accessibility tools, and communication aids for the hearing-impaired. Furthermore, it lays the foundation for future advancements in SSL translation systems, fostering inclusive and equal opportunities for the deaf community. Future work includes expanding the existing datasets to further improve the accuracy and generalization of the SSL translation system. Additionally, the development of a dedicated mobile application would enhance the accessibility and convenience of SSL translation on handheld devices. Furthermore, efforts will be made to enhance the current application for educational purposes, enabling individuals to learn and practice SSL more effectively. Another area of future exploration involves enabling two-way communication, allowing seamless interaction between sign-language users and non-sign-language users.In conclusion, this paper presents a novel approach for converting Sinhala Sign Language gestures into grammatically correct sentences using NLP techniques in real time. The two-stage methodology, comprising an LSTM model for sign detection and translation and an NMT model for grammar correction, achieves high accuracy rates of 94% and 98%, respectively. By addressing the lack of grammar checking in existing SSL translation research, this work contributes significantly to the development of more accurate and reliable SSL translation systems, thereby fostering effective communication and inclusivity for the hearing-impaired community

Keywords: Sinhala sign language, sign Language, NLP, LSTM, NMT

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49 Understanding Systemic Barriers (and Opportunities) to Increasing Uptake of Subcutaneous Medroxy Progesterone Acetate Self-Injection in Health Facilities in Nigeria

Authors: Oluwaseun Adeleke, Samuel O. Ikani, Fidelis Edet, Anthony Nwala, Mopelola Raji, Simeon Christian Chukwu

Abstract:

Background: The DISC project collaborated with partners to implement demand creation and service delivery interventions, including the MoT (Moment of Truth) innovation, in over 500 health facilities across 15 states. This has increased the voluntary conversion rate to self-injection among women who opt for injectable contraception. While some facilities recorded an increasing trend in key performance indicators, few others persistently performed sub-optimally due to provider and system-related barriers. Methodology: Twenty-two facilities performing sub-optimally were selected purposively from three Nigerian states. Low productivity was appraised using low reporting rates and poor SI conversion rates as indicators. Interviews were conducted with health providers across these health facilities using a rapid diagnosis tool. The project also conducted a data quality assessment that evaluated the veracity of data elements reported across the three major sources of family planning data in the facility. Findings: The inability and sometimes refusal of providers to support clients to self-inject effectively was associated with the misunderstanding of its value to their work experience. It was also observed that providers still held a strong influence over clients’ method choices. Furthermore, providers held biases and misconceptions about DMPA-SC that restricted the access of obese clients and new acceptors to services – a clear departure from the recommendations of the national guidelines. Additionally, quality of care standards was compromised because job aids were not used to inform service delivery. Facilities performing sub-optimally often under-reported DMPA-SC utilization data, and there were multiple uncoordinated responsibilities for recording and reporting. Additionally, data validation meetings were not regularly convened, and these meetings were ineffective in authenticating data received from health facilities. Other reasons for sub-optimal performance included poor documentation and tracking of stock inventory resulting in commodity stockouts, low client flow because of poor positioning of health facilities, and ineffective messaging. Some facilities lacked adequate human and material resources to provide services effectively and received very few supportive supervision visits. Supportive supervision visits and Data Quality Audits have been useful to address the aforementioned performance barriers. The project has deployed digital DMPA-SC self-injection checklists that have been aligned with nationally approved templates. During visits, each provider and community mobilizer is accorded special attention by the supervisor until he/she can perform procedures in line with best practice (protocol). Conclusion: This narrative provides a summary of a range of factors that identify health facilities performing sub-optimally in their provision of DMPA-SC services. Findings from this assessment will be useful during project design to inform effective strategies. As the project enters its final stages of implementation, it is transitioning high-impact activities to state institutions in the quest to sustain the quality of service beyond the tenure of the project. The project has flagged activities, as well as created protocols and tools aimed at placing state-level stakeholders at the forefront of improving productivity in health facilities.

Keywords: family planning, contraception, DMPA-SC, self-care, self-injection, barriers, opportunities, performance

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48 Triple Immunotherapy to Overcome Immune Evasion by Tumors in a Melanoma Mouse Model

Authors: Mary-Ann N. Jallad, Dalal F. Jaber, Alexander M. Abdelnoor

Abstract:

Introduction: Current evidence confirms that both innate and adaptive immune systems are capable of recognizing and abolishing malignant cells. The emergence of cancerous tumors in patients is, therefore, an indication that certain cancer cells can resist elimination by the immune system through a process known as “immune evasion”. In fact, cancer cells often exploit regulatory mechanisms to escape immunity. Such mechanisms normally exist to control the immune responses and prohibit exaggerated or autoimmune reactions. Recently, immunotherapies have shown promising yet limited results. Therefore this study investigates several immunotherapeutic combinations and devises a triple immunotherapy which harnesses the innate and acquired immune responses towards the annihilation of malignant cells through overcoming their ability of immune evasion, consequently hampering malignant progression and eliminating established tumors. The aims of the study are to rule out acute/chronic toxic effects of the proposed treatment combinations, to assess the effect of these combinations on tumor growth and survival rates, and to investigate potential mechanisms underlying the phenotypic results through analyzing serum levels of anti-tumor cytokines, angiogenic factors and tumor progression indicator, and the tumor-infiltrating immune-cells populations. Methodology: For toxicity analysis, cancer-free C57BL/6 mice are randomized into 9 groups: Group 1 untreated, group 2 treated with sterile saline (solvent of used treatments), group 3 treated with Monophosphoryl-lipid-A, group 4 with anti-CTLA4-antibodies, group 5 with 1-Methyl-Tryptophan (Indolamine-Dioxygenase-1 inhibitor), group 6 with both MPLA and anti-CTLA4-antibodies, group 7 with both MPLA and 1-MT, group 8 with both anti-CTLA4-antibodies and 1-MT, and group 9 with all three: MPLA, anti-CTLA4-antibodies and 1-MT. Mice are monitored throughout the treatment period and for three following months. At that point, histological sections from their main organs are assessed. For tumor progression and survival analysis, a murine melanoma model is generated by injecting analogous mice with B16F10 melanoma cells. These mice are segregated into the listed nine groups. Their tumor size and survival are monitored. For a depiction of underlying mechanisms, melanoma-bearing mice from each group are sacrificed at several time-points. Sera are tested to assess the levels of Interleukin-12 (IL-12), Vascular-Endothelial-Growth Factor (VEGF), and S100B. Furthermore, tumors are excised for analysis of infiltrated immune cell populations including T-cells, macrophages, natural killer cells and immune-regulatory cells. Results: Toxicity analysis shows that all treated groups present no signs of neither acute nor chronic toxicity. Their appearance and weights were comparable to those of control groups throughout the treatment period and for the following 3 months. Moreover, histological sections from their hearts, kidneys, lungs, and livers were normal. Work is ongoing for completion of the remaining study aims. Conclusion: Toxicity was the major concern for the success of the proposed comprehensive combinational therapy. Data generated so far ruled out any acute or chronic toxic effects. Consequently, ongoing work is quite promising and may significantly contribute to the development of more effective immunotherapeutic strategies for the treatment of cancer patients.

Keywords: cancer immunotherapy, check-point blockade, combination therapy, melanoma

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47 Cardiolipin-Incorporated Liposomes Carrying Curcumin and Nerve Growth Factor to Rescue Neurons from Apoptosis for Alzheimer’s Disease Treatment

Authors: Yung-Chih Kuo, Che-Yu Lin, Jay-Shake Li, Yung-I Lou

Abstract:

Curcumin (CRM) and nerve growth factor (NGF) were entrapped in liposomes (LIP) with cardiolipin (CL) to downregulate the phosphorylation of mitogen-activated protein kinases for Alzheimer’s disease (AD) management. AD belongs to neurodegenerative disorder with a gradual loss of memory, yielding irreversible dementia. CL-conjugated LIP loaded with CRM (CRM-CL/LIP) and that with NGF (NGF-CL/LIP) were applied to AD models of SK-N-MC cells and Wistar rats with an insult of β-amyloid peptide (Aβ). Lipids comprising 1,2-dipalmitoyl-sn-glycero-3- phosphocholine (Avanti Polar Lipids, Alabaster, AL), 1',3'-bis[1,2- dimyristoyl-sn-glycero-3-phospho]-sn-glycerol (CL; Avanti Polar Lipids), 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N- [methoxy(polyethylene glycol)-2000] (Avanti Polar Lipids), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[carboxy(polyethylene glycol)-2000] (Avanti Polar Lipids) and CRM (Sigma–Aldrich, St. Louis, MO) were dissolved in chloroform (J. T. Baker, Phillipsburg, NJ) and condensed using a rotary evaporator (Panchum, Kaohsiung, Taiwan). Human β-NGF (Alomone Lab, Jerusalem, Israel) was added in the aqueous phase. Wheat germ agglutinin (WGA; Medicago AB, Uppsala, Sweden) was grafted on LIP loaded with CRM for (WGA-CRM-LIP) and CL-conjugated LIP loaded with CRM (WGA-CRM-CL/LIP) using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (Sigma–Aldrich) and N-hydroxysuccinimide (Alfa Aesar, Ward Hill, MA). The protein samples of SK-N-MC cells (American Type Tissue Collection, Rockville, MD) were used for sodium dodecyl sulfate (Sigma–Aldrich) polyacrylamide gel (Sigma–Aldrich) electrophoresis. In animal study, the LIP formulations were administered by intravenous injection via a tail vein of male Wistar rats (250–280 g, 8 weeks, BioLasco, Taipei, Taiwan), which were housed in the Animal Laboratory of National Chung Cheng University in accordance with the institutional guidelines and the guidelines of Animal Protection Committee under the Council of Agriculture of the Republic of China. We found that CRM-CL/LIP could inhibit the expressions of phosphorylated p38 (p-p38), p-Jun N-terminal kinase (p-JNK), and p-tau protein at serine 202 (p-Ser202) to retard the neuronal apoptosis. Free CRM and released CRM from CRM-LIP and CRM-CL/LIP were not in a straightforward manner to effectively inhibit the expression of p-p38 and p-JNK in the cytoplasm. In addition, NGF-CL/LIP enhanced the quantities of p-neurotrophic tyrosine kinase receptor type 1 (p-TrkA) and p-extracellular-signal-regulated kinase 5 (p-ERK5), preventing the Aβ-induced degeneration of neurons. The membrane fusion of NGF-LIP activated the ERK5 pathway and the targeting capacity of NGF-CL/LIP enhanced the possibility of released NGF to affect the TrkA level. Moreover, WGA-CRM-LIP improved the permeation of CRM across the blood–brain barrier (BBB) and significantly reduced the Aβ plaque deposition and malondialdehyde level and increased the percentage of normal neurons and cholinergic function in the hippocampus of AD rats. This was mainly because the encapsulated CRM was protected by LIP against a rapid degradation in the blood. Furthermore, WGA on LIP could target N-acetylglucosamine on endothelia and increased the quantity of CRM transported across the BBB. In addition, WGA-CRM-CL/LIP could be effective in suppressing the synthesis of acetylcholinesterase and reduced the decomposition of acetylcholine for better neurotransmission. Based on the in vitro and in vivo evidences, WGA-CRM-CL/LIP can rescue neurons from apoptosis in the brain and can be a promising drug delivery system for clinical AD therapy.

Keywords: Alzheimer’s disease, β-amyloid, liposome, mitogen-activated protein kinase

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46 Molecular Signaling Involved in the 'Benzo(a)Pyrene' Induced Germ Cell DNA Damage and Apoptosis: Possible Protection by Natural Aryl Hydrocarbon Receptor Antagonist and Anti-Tumor Agent

Authors: Kuladip Jana

Abstract:

Benzo(a)pyrene [B(a)P] is an environmental toxicant present mostly in cigarette smoke and car exhaust, is an aryl hydrocarbon receptor (AhR) ligand that exerts its toxic effects on both male and female reproductive systems. In this study, the effect of B(a)P at different doses (0.1, 0.25, 0.5, 1 and 5 mg /kg body weight) was studied on male reproductive system of rat. A significant decrease in cauda epididymal sperm count and motility along with the presence of sperm head abnormalities and altered epididymal and testicular histology were documented following B(a)P treatment. B(a)P treatment resulted apoptotic sperm cells as observed by TUNEL and Annexin V-PI assay with increased ROS, altered sperm mitochondrial membrane potential (ΔΨm) with a simultaneous decrease in the activity of antioxidant enzymes and GSH status. TUNEL positive apoptotic cells also observed in testis as well as isolated germ and Leydig cells following B(a)P exposure. Western Blot analysis revealed the activation of p38MAPK, cytosolic translocation of cytochrome-c, up-regulation of Bax and inducible nitric oxide synthase (iNOS) with cleavage of PARP and down-regulation of BCl2 in testis upon B(a)P treatment. The protein and mRNA levels of testicular key steroidogenesis regulatory proteins like StAR, cytochrome P450 IIA1 (CYPIIA1), 3β HSD, 17β HSD showed a significant decrease in a dose dependent manner while an increase in the expression of cytochrome P450 1A1 (CYP1A1), Aryl hydrocarbon Receptor (AhR), active caspase- 9 and caspase- 3 following B(a)P exposure. We conclude that exposure of benzo(a)pyrene caused testicular gamatogenic and steroidogenic disorders by induction of oxidative stress, inhibition of StAR and other steroidogenic enzymes along with activation of p38MAPK and initiated caspase-3 mediated germ and Leydig cell apoptosis.The possible protective role of naturally occurring phytochemicals against B(a)P induced testicular toxicity needs immediate consideration. Curcumin and resveratrol separately were found to protect against B(a)P induced germ cell apoptosis, and their combinatorial effect was more significant. Our present study in isolated testicular germ cell population from adult male Wistar rats, highlighted their synergistic protective effect against B(a)P induced germ cell apoptosis. Curcumin-resveratrol co-treatment decreased the expression of pro-apoptotic proteins like cleaved caspase 3,8,9, cleaved PARP, Apaf1, FasL, tBid. Curcumin-resveratrol co-treatment decreased Bax/Bcl2 ratio, mitochondria to cytosolic translocation of cytochrome c and activated the survival protein Akt. Curcumin-resveratrol decreased the expression of p53 dependent apoptotic genes like Fas, FasL, Bax, Bcl2, Apaf1.Curcumin-resveratrol co-treatment thus prevented B(a)P induced germ cell apoptosis. B(a)P induced testicular ROS generation and oxidative stress were significantly ameliorated with curcumin and resveratrol. Curcumin-resveratrol co-treatment prevented B(a)P induced nuclear translocation of AhR and CYP1A1 production. The combinatorial treatment significantly inhibited B(a)P induced ERK 1/2, p38 MAPK and JNK 1/2 activation. B(a)P treatment increased the expression of p53 and its phosphorylation (p53 ser 15). Curcumin-resveratrol co-treatment significantly decreased p53 level and its phosphorylation (p53 ser 15). The study concludes that curcumin-resveratrol synergistically modulated MAPKs and p53, prevented oxidative stress, regulated the expression of pro and anti-apoptotic proteins as well as the proteins involved in B(a)P metabolism thus protected germ cells from B(a)P induced apoptosis.

Keywords: benzo(a)pyrene, germ cell, apoptosis, oxidative stress, resveratrol, curcumin

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45 Low-Cost Aviation Solutions to Strengthen Counter-Poaching Efforts in Kenya

Authors: Kuldeep Rawat, Michael O'Shea, Maureen McGough

Abstract:

The paper will discuss a National Institute of Justice (NIJ) funded project to provide cost-effective aviation technologies and research to support counter-poaching operations related to endangered, protected, and/or regulated wildlife. The goal of this project is to provide cost-effective aviation technology and research support to Kenya Wildlife Service (KWS) in their counter-poaching efforts. In pursuit of this goal, Elizabeth City State University (ECSU) is assisting the National Institute of Justice (NIJ) in enhancing the Kenya Wildlife Service’s aviation technology and related capacity to meet its counter-poaching mission. Poaching, at its core, is systemic as poachers go to the most extreme lengths to kill high target species such as elephant and rhino. These high target wildlife species live in underdeveloped or impoverished nations, where poachers find fewer barriers to their operations. In Kenya, with fifty-nine (59) parks and reserves, spread over an area of 225,830 square miles (584,897 square kilometers) adequate surveillance on the ground is next to impossible. Cost-effective aviation surveillance technologies, based on a comprehensive needs assessment and operational evaluation, are needed to curb poaching and effectively prevent wildlife trafficking. As one of the premier law enforcement Air Wings in East Africa, KWS plays a crucial role in Kenya, not only in counter-poaching and wildlife conservation efforts, but in aerial surveillance, counterterrorism and national security efforts as well. While the Air Wing has done, a remarkable job conducting aerial patrols with limited resources, additional aircraft and upgraded technology should significantly advance the Air Wing’s ability to achieve its wildlife protection mission. The project includes: (i) Needs Assessment of the KWS Air Wing, to include the identification of resources, current and prospective capacity, operational challenges and priority goals for expansion, (ii) Acquisition of Low-Cost Aviation Technology to meet priority needs, and (iii) Operational Evaluation of technology performance, with a focus on implementation and effectiveness. The Needs Assessment reflects the priorities identified through two site visits to the KWS Air Wing in Nairobi, Kenya, as well as field visits to multiple national parks receiving aerial support and interviewing/surveying KWS Air wing pilots and leadership. Needs Assessment identified some immediate technology needs that includes, GPS with upgrades, including weather application, Night flying capabilities, to include runway lights and night vision technology, Cameras and surveillance equipment, Flight tracking system and/or Emergency Position Indicating Radio Beacon, Lightweight ballistic-resistant body armor, and medical equipment, to include a customized stretcher and standard medical evacuation equipment. Results of this assessment, along with significant input from the KWS Air Wing, will guide the second phase of this project: technology acquisition. Acquired technology will then be evaluated in the field, with a focus on implementation and effectiveness. Results will ultimately be translated for any rural or tribal law enforcement agencies with comparable aerial surveillance missions and operational environments, and jurisdictional challenges, seeking to implement low-cost aviation technology. Results from Needs Assessment phase, including survey results and our ongoing technology acquisition and baseline operational evaluation will be discussed in the paper.

Keywords: aerial surveillance mission, aviation technology, counter-poaching, wildlife protection

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