Search results for: gly gold
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 583

Search results for: gly gold

73 Directional Dust Deposition Measurements: The Influence of Seasonal Changes and the Meteorological Conditions Influencing in Witbank Area and Carletonville Area

Authors: Maphuti Georgina Kwata

Abstract:

Coal mining in Mpumalanga Province is known of contributing to the atmospheric pollution from various activities. Gold mining in North-West Province is known of also contributing to the atmospheric pollution especially with the production of radon gas. In this research directional dust deposition gauge was used to measure source of direction and meteorological data was used to determine the wind rose blowing and the influence of the seasonal changes. Fourteen months of dust collection was undertaken in Witbank Area and Carletonville Area. The results shows that the sources of direction for Ericson Dam its East in February 2010 and Tip Area shows that the source of direction its West in October 2010. In the East direction there were mining operations, power stations which contributed to the East to be the sources of direction. In the West direction there were smelters, power stations and agricultural activities which contributed for the source of direction to be the West direction for Driefontein Mine: East Recreational Village Club. The East of Leslie Williams hospital is the source of direction which also indicated that there dust generating activities such as mining operation, agricultural activities. The meteorological results for Emalahleni Area in summer and winter the wind rose blow with wind speed of 5-10 ms-1 from the East sector. Annual average for the wind rose blow its East South eastern sector with 20 ms-1 and day time the wind rose from northwestern sector with excess of 20 ms-1. The night time wind direction East-eastern direction with a maximum wind speed of 20 ms-1. The meteorogical results for Driefontein Mine show that North-western sector and north-eastern sector wind rose is blowing with 5-10 ms-1 win speed. Day time wind blows from the West sector and night time wind blows from the north sector. In summer the wind blows North-east sector with 5-10 ms-1 and winter wind blows from North-west and it’s also predominant. In spring wind blows from north-east. The conclusion is that not only mining operation where the directional dust deposit gauge were installed contributed to the source of direction also the power stations, smelters, and other activities nearby the mining operation contributed. The recommendations are the dust suppressant for unpaved roads should be used on a regular basis and there should be monitoring of the weather conditions (the wind speed and direction prior to blasting to ensure minimal emissions).

Keywords: directional dust deposition gauge, BS part 5 1747 dust deposit gauge, wind rose, wind blowing

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72 Hydrogeophysical Investigations And Mapping of Ingress Channels Along The Blesbokspruit Stream In The East Rand Basin Of The Witwatersrand, South Africa

Authors: Melvin Sethobya, Sithule Xanga, Sechaba Lenong, Lunga Nolakana, Gbenga Adesola

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Mining has been the cornerstone of the South African economy for the last century. Most of the gold mining in South Africa was conducted within the Witwatersrand basin, which contributed to the rapid growth of the city of Johannesburg and capitulated the city to becoming the business and wealth capital of the country. But with gradual depletion of resources, a stoppage in the extraction of underground water from mines and other factors relating to survival of the mining operations over a lengthy period, most of the mines were abandoned and left to pollute the local waterways and groundwater with toxins, heavy metal residue and increased acid mine drainage ensued. The Department of Mineral Resources and Energy commissioned a project whose aim is to monitor, maintain, and mitigate the adverse environmental impacts of polluted water mine water flowing into local streams affecting local ecosystems and livelihoods downstream. As part of mitigation efforts, the diagnosis and monitoring of groundwater or surface water polluted sites has become important. Geophysical surveys, in particular, Resistivity and Magnetics surveys, were selected as some of most suitable techniques for investigation of local ingress points along of one the major streams cutting through the Witwatersrand basin, namely the Blesbokspruit, which is found in the eastern part of the basin. The aim of the surveys was to provide information that could be used to assist in determining possible water loss/ ingress from the Blesbokspriut stream. Modelling of geophysical surveys results offered an in-depth insight into the interaction and pathways of polluted water through mapping of possible ingress channels near the Blesbokspruit. The resistivity - depth profile of the surveyed site exhibit a three(3) layered model with low resistivity values (10 to 200 Ω.m) overburden, which is underlain by a moderate resistivity weathered layer (>300 Ω.m), which sits on a more resistive crystalline bedrock (>500 Ω.m). Two locations of potential ingress channels were mapped across the two traverses at the site. The magnetic survey conducted at the site mapped a major NE-SW trending regional linearment with a strong magnetic signature, which was modeled to depth beyond 100m, with the potential to act as a conduit for dispersion of stream water away from the stream, as it shared a similar orientation with the potential ingress channels as mapped using the resistivity method.

Keywords: eletrictrical resistivity, magnetics survey, blesbokspruit, ingress

Procedia PDF Downloads 63
71 Effect of Self-Lubricating Carbon Materials on the Tribological Performance of Ultra-High Molecular Weight Polyethylene

Authors: Nayeli Camacho, Fernanda Lara-Perez, Carolina Ortega-Portilla, Diego G. Espinosa-Arbelaez, Juan M. Alvarado-Orozco, Guillermo C. Mondragon-Rodriguez

Abstract:

Ultra-high molecular weight polyethylene (UHMWPE) has been the gold standard material for total knee replacements for almost five decades. Wear damage to UHMWPE articulating surface is inevitable due to the natural sliding and rolling movements of the knee. This generates a considerable amount of wear debris, which results in mechanical instability of the joint, reduces joint mobility, increases pain with detrimental biologic responses, and causes component loosening. The presence of wear particles has been closely related to adverse reactions in the knee joint surrounding tissue, especially for particles in the range of 0.3 to 2 μm. Carbon-based materials possess excellent mechanical properties and have shown great promise in tribological applications. In this study, diamond-like carbon coatings (DLC) and carbon nanotubes (CNTs) were used to decrease the wear rate of ultra-high molecular weight polyethylene. A titanium doped DLC (Ti-DLC) was deposited by magnetron sputtering on stainless steel precision spheres while CNTs were used as a second phase reinforcement in UHMWPE at a concentration of 1.25 wt.%. A comparative tribological analysis of the wear of UHMWPE and UHMWPE-CNTs with a stainless steel counterpart with and without Ti-DLC coating is presented. The experimental wear testing was performed on a pin-on-disc tribometer under dry conditions, using a reciprocating movement with a load of 1 N at a frequency of 2 Hz for 100,000 and 200,000 cycles. The wear tracks were analyzed with high-resolution scanning electron microscopy to determine wear modes and observe the size and shape of the wear debris. Furthermore, profilometry was used to study the depth of the wear tracks and to map the wear of the articulating surface. The wear tracks at 100,000 and 200,000 cycles on all samples were relatively shallow, and they were in the range of average roughness. It was observed that the Ti-DLC coating decreases the mass loss in the UHMWPE and the depth of the wear track. The combination of both carbon-based materials decreased the material loss compared to the system of stainless steel and UHMWPE. Burnishing of the surface was the predominant wear mode observed with all the systems, more subtle for the systems with Ti-DLC coatings. Meanwhile, in the system composed of stainless steel-UHMWPE, the intrinsic surface roughness of the material was completely replaced by the wear tracks.

Keywords: CNT reinforcement, self-lubricating materials, Ti-DLC, UHMWPE tribological performance

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70 A 1T1R Nonvolatile Memory with Al/TiO₂/Au and Sol-Gel Processed Barium Zirconate Nickelate Gate in Pentacene Thin Film Transistor

Authors: Ke-Jing Lee, Cheng-Jung Lee, Yu-Chi Chang, Li-Wen Wang, Yeong-Her Wang

Abstract:

To avoid the cross-talk issue of only resistive random access memory (RRAM) cell, one transistor and one resistor (1T1R) architecture with a TiO₂-based RRAM cell connected with solution barium zirconate nickelate (BZN) organic thin film transistor (OTFT) device is successfully demonstrated. The OTFT were fabricated on a glass substrate. Aluminum (Al) as the gate electrode was deposited via a radio-frequency (RF) magnetron sputtering system. The barium acetate, zirconium n-propoxide, and nickel II acetylacetone were synthesized by using the sol-gel method. After the BZN solution was completely prepared using the sol-gel process, it was spin-coated onto the Al/glass substrate as the gate dielectric. The BZN layer was baked at 100 °C for 10 minutes under ambient air conditions. The pentacene thin film was thermally evaporated on the BZN layer at a deposition rate of 0.08 to 0.15 nm/s. Finally, gold (Au) electrode was deposited using an RF magnetron sputtering system and defined through shadow masks as both the source and drain. The channel length and width of the transistors were 150 and 1500 μm, respectively. As for the manufacture of 1T1R configuration, the RRAM device was fabricated directly on drain electrodes of TFT device. A simple metal/insulator/metal structure, which consisting of Al/TiO₂/Au structures, was fabricated. First, Au was deposited to be a bottom electrode of RRAM device by RF magnetron sputtering system. Then, the TiO₂ layer was deposited on Au electrode by sputtering. Finally, Al was deposited as the top electrode. The electrical performance of the BZN OTFT was studied, showing superior transfer characteristics with the low threshold voltage of −1.1 V, good saturation mobility of 5 cm²/V s, and low subthreshold swing of 400 mV/decade. The integration of the BZN OTFT and TiO₂ RRAM devices was finally completed to form 1T1R configuration with low power consumption of 1.3 μW, the low operation current of 0.5 μA, and reliable data retention. Based on the I-V characteristics, the different polarities of bipolar switching are found to be determined by the compliance current with the different distribution of the internal oxygen vacancies used in the RRAM and 1T1R devices. Also, this phenomenon can be well explained by the proposed mechanism model. It is promising to make the 1T1R possible for practical applications of low-power active matrix flat-panel displays.

Keywords: one transistor and one resistor (1T1R), organic thin-film transistor (OTFT), resistive random access memory (RRAM), sol-gel

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69 Successful Excision of Lower Lip Mucocele Using 2780 nm Er,Cr:YSGG Laser

Authors: Lubna M. Al-Otaibi

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Mucocele is a common benign neoplasm of the oral cavity and the most common after fibroma. The lesion develops as a result of retention or extravasation of mucous material from minor salivary glands. Extravasation type of mucocele results from trauma and mostly occurs in the lower lip of young patients. The various treatment options available for the treatment of mucocele are associated with a relatively high incidence of recurrence making surgical intervention necessary for a permanent cure. The conventional surgical procedure, however, arouses apprehension in the patient and is associated with bleeding and postoperative pain. Recently, treatment of mucocele with lasers has become a viable treatment option. Various types of lasers are being used and are preferable over the conventional surgical procedure as they provide good hemostasis, reduced postoperative swelling and pain, reduced bacterial population, lesser need for suturing, faster healing and low recurrence rates. Er,Cr:YSGG is a solid-state laser with great affinity to water molecule. Its hydrokinetic cutting action allows it to work effectively on hydrated tissues without any thermal damage. However, up to date, only a few studies have reported its use in the removal of lip mucocele, especially in children. In this case, a 6 year old female patient with history of trauma to the lower lip presented with a soft, sessile, whitish-bluish 4 mm papule. The lesion was present for approximately four months and was fluctuant in size. The child developed a habit of biting the lesion causing injury, bleeding and discomfort. Surgical excision under local anaesthesia was performed using 2780 nm Er,Cr:YSGG Laser (WaterLase iPlus, Irvine, CA) with a Gold handpiece and MZ6 tip (3.5w, 50 Hz, 20% H2O, 20% Air, S mode). The tip was first applied in contact mode with focused beam using the Circumferential Incision Technique (CIT) to excise the tissue followed by the removal of the underlying causative minor salivary gland. Bleeding was stopped using Laser Dry Bandage setting (0.5w, 50 Hz, 1% H2O, 20% Air, S mode) and no suturing was needed. Safety goggles were worn and high-speed suction was used for smoke evacuation. Mucocele excision using 2780 nm Er,Cr:YSGG laser was rapid, easy to perform with excellent precision and allowed for histopathological examination of the excised tissue. The patient was comfortable and there were minimum bleeding and no sutures, postoperative pain, scarring or recurrence. Laser assisted mucocele excision appears to have efficient and reliable benefits in young patients and should be considered as an alternative to conventional surgical and non-surgical techniques.

Keywords: Erbium, excision, laser, lip, mucocele

Procedia PDF Downloads 236
68 The Diagnostic Utility and Sensitivity of the Xpert® MTB/RIF Assay in Diagnosing Mycobacterium tuberculosis in Bone Marrow Aspirate Specimens

Authors: Nadhiya N. Subramony, Jenifer Vaughan, Lesley E. Scott

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In South Africa, the World Health Organisation estimated 454000 new cases of Mycobacterium tuberculosis (M.tb) infection (MTB) in 2015. Disseminated tuberculosis arises from the haematogenous spread and seeding of the bacilli in extrapulmonary sites. The gold standard for the detection of MTB in bone marrow is TB culture which has an average turnaround time of 6 weeks. Histological examinations of trephine biopsies to diagnose MTB also have a time delay owing mainly to the 5-7 day processing period prior to microscopic examination. Adding to the diagnostic delay is the non-specific nature of granulomatous inflammation which is the hallmark of MTB involvement of the bone marrow. A Ziehl-Neelson stain (which highlights acid-fast bacilli) is therefore mandatory to confirm the diagnosis but can take up to 3 days for processing and evaluation. Owing to this delay in diagnosis, many patients are lost to follow up or remain untreated whilst results are awaited, thus encouraging the spread of undiagnosed TB. The Xpert® MTB/RIF (Cepheid, Sunnyvale, CA) is the molecular test used in the South African national TB program as the initial diagnostic test for pulmonary TB. This study investigates the optimisation and performance of the Xpert® MTB/RIF on bone marrow aspirate specimens (BMA), a first since the introduction of the assay in the diagnosis of extrapulmonary TB. BMA received for immunophenotypic analysis as part of the investigation into disseminated MTB or in the evaluation of cytopenias in immunocompromised patients were used. Processing BMA on the Xpert® MTB/RIF was optimised to ensure bone marrow in EDTA and heparin did not inhibit the PCR reaction. Inactivated M.tb was spiked into the clinical bone marrow specimen and distilled water (as a control). A volume of 500mcl and an incubation time of 15 minutes with sample reagent were investigated as the processing protocol. A total of 135 BMA specimens had sufficient residual volume for Xpert® MTB/RIF testing however 22 specimens (16.3%) were not included in the final statistical analysis as an adequate trephine biopsy and/or TB culture was not available. Xpert® MTB/RIF testing was not affected by BMA material in the presence of heparin or EDTA, but the overall detection of MTB in BMA was low compared to histology and culture. Sensitivity of the Xpert® MTB/RIF compared to both histology and culture was 8.7% (95% confidence interval (CI): 1.07-28.04%) and sensitivity compared to histology only was 11.1% (95% CI: 1.38-34.7%). Specificity of the Xpert® MTB/RIF was 98.9% (95% CI: 93.9-99.7%). Although the Xpert® MTB/RIF generates a faster result than histology and TB culture and is less expensive than culture and drug susceptibility testing, the low sensitivity of the Xpert® MTB/RIF precludes its use for the diagnosis of MTB in bone marrow aspirate specimens and warrants alternative/additional testing to optimise the assay.

Keywords: bone marrow aspirate , extrapulmonary TB, low sensitivity, Xpert® MTB/RIF

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67 Inertial Spreading of Drop on Porous Surfaces

Authors: Shilpa Sahoo, Michel Louge, Anthony Reeves, Olivier Desjardins, Susan Daniel, Sadik Omowunmi

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The microgravity on the International Space Station (ISS) was exploited to study the imbibition of water into a network of hydrophilic cylindrical capillaries on time and length scales long enough to observe details hitherto inaccessible under Earth gravity. When a drop touches a porous medium, it spreads as if laid on a composite surface. The surface first behaves as a hydrophobic material, as liquid must penetrate pores filled with air. When contact is established, some of the liquid is drawn into pores by a capillarity that is resisted by viscous forces growing with length of the imbibed region. This process always begins with an inertial regime that is complicated by possible contact pinning. To study imbibition on Earth, time and distance must be shrunk to mitigate gravity-induced distortion. These small scales make it impossible to observe the inertial and pinning processes in detail. Instead, in the International Space Station (ISS), astronaut Luca Parmitano slowly extruded water spheres until they touched any of nine capillary plates. The 12mm diameter droplets were large enough for high-speed GX1050C video cameras on top and side to visualize details near individual capillaries, and long enough to observe dynamics of the entire imbibition process. To investigate the role of contact pinning, a text matrix was produced which consisted nine kinds of porous capillary plates made of gold-coated brass treated with Self-Assembled Monolayers (SAM) that fixed advancing and receding contact angles to known values. In the ISS, long-term microgravity allowed unambiguous observations of the role of contact line pinning during the inertial phase of imbibition. The high-speed videos of spreading and imbibition on the porous plates were analyzed using computer vision software to calculate the radius of the droplet contact patch with the plate and height of the droplet vs time. These observations are compared with numerical simulations and with data that we obtained at the ESA ZARM free-fall tower in Bremen with a unique mechanism producing relatively large water spheres and similarity in the results were observed. The data obtained from the ISS can be used as a benchmark for further numerical simulations in the field.

Keywords: droplet imbibition, hydrophilic surface, inertial phase, porous medium

Procedia PDF Downloads 139
66 The Global Children’s Challenge Program: Pedometer Step Count in an Australian School

Authors: D. Hilton

Abstract:

The importance and significance of this research is based upon the fundamental knowledge reported in the scientific literature that physical activity is inversely associated with obesity. In addition, it is recognized there is a global epidemic of sedentariness while at the same time it is known that morbidity and mortality are associated with physical inactivity and as a result of overweight or obesity. Hence this small study in school students is an important area of research in our community. An application submitted in 2005 for the inaugural Public Health Education Research Trust [PHERT] Post Graduate Research Scholarship scheme organized by the Public Health Association of Australia [PHAA] was awarded 3rd place within Australia. The author and title was: D. Hilton, Methods to increase physical activity in school aged children [literature review, a trial using pedometers and a policy paper]. Third place is a good result, however this did not secure funding for the project, as only first place received $5000 funding. Some years later within Australia, a program commenced called the Global Children's Challenge [GCC]. Given details of the 2005 award above were included an application submission prepared for Parkhill Primary School [PPS] which is located in Victoria, Australia was successful. As a result, an excited combined grade 3/ 4 class at the school [27 students] in 2012 became recipients of these free pedometers. Ambassadors for the program were Mrs Catherine Freeman [OAM], Olympic Gold Medalist – Sydney 2000 [400 meters], while another ambassador was Mr Colin Jackson [CBE] who is a Welsh former sprint and hurdling athlete. In terms of PPS and other schools involved in 2012, website details show that the event started on 19th Sep 2012 and students were to wear the pedometer every day for 50 days [at home and at school] aiming for the recommended 15,000 steps/day recording steps taken in a booklet provided. After the finish, an analysis of the average step count for this school showed that the average steps taken / day was 14, 003 [however only a small percentage of students returned the booklets and units] as unfortunately the dates for the program coincided with school holidays so some students either forgot or misplaced the units / booklets. Unfortunately funding for this program ceased in 2013, however the lasting impact of the trial on student’s knowledge and awareness remains and in fact becomes a good grounding for students in how to monitor basic daily physical activity using a method that is easy, fun, low cost and readily accessible.

Keywords: walking, physical activity, exercise, Australian school

Procedia PDF Downloads 309
65 Bulbar Conjunctival Kaposi's Sarcoma Unmasked by Immune Reconstitution Syndrome

Authors: S. Mohd Afzal, R. O'Connell

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Kaposi's sarcoma (KS) is the most common HIV-related cancer, and ocular manifestations constitute at least 25% of all KS cases. However, ocular presentations often occur in the context of systemic KS, and isolated lesions are rare. We report a unique case of ocular KS masquerading as subconjunctival haemorrhage, and only developing systemic manifestations after initiation of HIV treatment. Case: A 49-year old man with previous hypertensive stroke and newly diagnosed HIV infection presented with an acutely red left eye following repeated bouts of coughing. Given the convincing history of poorly controlled hypertension and cough, a diagnosis of subconjunctival haemorrhage was made. Over the next week, his ocular lesion began to improve and he subsequently started anti-retroviral therapy. Prior to receiving anti-retroviral therapy, his CD4+ lymphocyte count was 194 cells/mm3 with HIV viral load greater than 1 million/ml. This rapidly improved to a viral load of 150 copies/ml within 2 weeks of starting treatment. However, a few days after starting HIV treatment, his ocular lesion recurred. Ophthalmic examination was otherwise normal. He also developed widespread lymphadenopathy and multiple dark lesions on his torso. Histology and virology confirmed KS, systemically triggered by Immune Reconstitution Syndrome (KS-IRIS). The patient has since undergone chemotherapy successfully. Discussion: Kaposi's sarcoma is an atypical tumour caused by human herpesvirus 8 (HHV-8), also known as Kaposi’s sarcoma-associated herpesvirus (KSHV). In immunosuppressed patients, KSHV can also cause lymphoproliferative disorders such as primary effusion lymphoma and Castleman's disease (in our patient’s case, this was excluded through histological analysis of lymph nodes). KSHV is one of the seven currently known human oncoviruses, and its pathogenesis is poorly understood. Up to 13% of patients with HIV-related KS experience worsening of the disease after starting anti-retroviral treatment, due to a sudden increase in CD4 cell counts. Histology remains the diagnostic gold standard. Current British HIV Association (BHIVA) guidelines recommend treatment using anti-retroviral drugs, with either intralesional vinblastine for local disease or systemic chemotherapy for disseminated KS. Conclusion: This case is unique as ocular KS as initial presentation is rare and our patient's diagnosis was only made after systemic lesions were triggered by immune reconstitution. KS should be considered as an important differential diagnosis for red eyes in all patients at risk of acquiring HIV infection.

Keywords: human herpesvirus 8, human immunodeficiency virus, immune reconstitution syndrome, Kaposi’s sarcoma, Kaposi’s sarcoma-associated herpesvirus

Procedia PDF Downloads 336
64 Selective Extraction of Lithium from Native Geothermal Brines Using Lithium-ion Sieves

Authors: Misagh Ghobadi, Rich Crane, Karen Hudson-Edwards, Clemens Vinzenz Ullmann

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Lithium is recognized as the critical energy metal of the 21st century, comparable in importance to coal in the 19th century and oil in the 20th century, often termed 'white gold'. Current global demand for lithium, estimated at 0.95-0.98 million metric tons (Mt) of lithium carbonate equivalent (LCE) annually in 2024, is projected to rise to 1.87 Mt by 2027 and 3.06 Mt by 2030. Despite anticipated short-term stability in supply and demand, meeting the forecasted 2030 demand will require the lithium industry to develop an additional capacity of 1.42 Mt of LCE annually, exceeding current planned and ongoing efforts. Brine resources constitute nearly 65% of global lithium reserves, underscoring the importance of exploring lithium recovery from underutilized sources, especially geothermal brines. However, conventional lithium extraction from brine deposits faces challenges due to its time-intensive process, low efficiency (30-50% lithium recovery), unsuitability for low lithium concentrations (<300 mg/l), and notable environmental impacts. Addressing these challenges, direct lithium extraction (DLE) methods have emerged as promising technologies capable of economically extracting lithium even from low-concentration brines (>50 mg/l) with high recovery rates (75-98%). However, most studies (70%) have predominantly focused on synthetic brines instead of native (natural/real), with limited application of these approaches in real-world case studies or industrial settings. This study aims to bridge this gap by investigating a geothermal brine sample collected from a real case study site in the UK. A Mn-based lithium-ion sieve (LIS) adsorbent was synthesized and employed to selectively extract lithium from the sample brine. Adsorbents with a Li:Mn molar ratio of 1:1 demonstrated superior lithium selectivity and adsorption capacity. Furthermore, the pristine Mn-based adsorbent was modified through transition metals doping, resulting in enhanced lithium selectivity and adsorption capacity. The modified adsorbent exhibited a higher separation factor for lithium over major co-existing cations such as Ca, Mg, Na, and K, with separation factors exceeding 200. The adsorption behaviour was well-described by the Langmuir model, indicating monolayer adsorption, and the kinetics followed a pseudo-second-order mechanism, suggesting chemisorption at the solid surface. Thermodynamically, negative ΔG° values and positive ΔH° and ΔS° values were observed, indicating the spontaneity and endothermic nature of the adsorption process.

Keywords: adsorption, critical minerals, DLE, geothermal brines, geochemistry, lithium, lithium-ion sieves

Procedia PDF Downloads 46
63 Evaluation of Cooperative Hand Movement Capacity in Stroke Patients Using the Cooperative Activity Stroke Assessment

Authors: F. A. Thomas, M. Schrafl-Altermatt, R. Treier, S. Kaufmann

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Stroke is the main cause of adult disability. Especially upper limb function is affected in most patients. Recently, cooperative hand movements have been shown to be a promising type of upper limb training in stroke rehabilitation. In these movements, which are frequently found in activities of daily living (e.g. opening a bottle, winding up a blind), the force of one upper limb has to be equally counteracted by the other limb to successfully accomplish a task. The use of standardized and reliable clinical assessments is essential to evaluate the efficacy of therapy and the functional outcome of a patient. Many assessments for upper limb function or impairment are available. However, the evaluation of cooperative hand movement tasks are rarely included in those. Thus, the aim of this study was (i) to develop a novel clinical assessment (CASA - Cooperative Activity Stroke Assessment) for the evaluation of patients’ capacity to perform cooperative hand movements and (ii) to test its inter- and interrater reliability. Furthermore, CASA scores were compared to current gold standard assessments for upper extremity in stroke patients (i.e. Fugl-Meyer Assessment, Box & Blocks Test). The CASA consists of five cooperative activities of daily living including (1) opening a jar, (2) opening a bottle, (3) open and closing of a zip, (4) unscrew a nut and (5) opening a clipbox. Here, the goal is to accomplish the tasks as fast as possible. In addition to the quantitative rating (i.e. time) which is converted to a 7-point scale, also the quality of the movement is rated in a 4-point scale. To test the reliability of CASA, fifteen stroke subjects were tested within a week twice by the same two raters. Intra-and interrater reliability was calculated using the intraclass correlation coefficient (ICC) for total CASA score and single items. Furthermore, Pearson-correlation was used to compare the CASA scores to the scores of Fugl-Meyer upper limb assessment and the box and blocks test, which were assessed in every patient additionally to the CASA. ICC scores of the total CASA score indicated an excellent- and single items established a good to excellent inter- and interrater reliability. Furthermore, the CASA score was significantly correlated to the Fugl-Meyer and Box & Blocks score. The CASA provides a reliable assessment for cooperative hand movements which are crucial for many activities of daily living. Due to its non-costly setup, easy and fast implementation, we suggest it to be well suitable for clinical application. In conclusion, the CASA is a useful tool in assessing the functional status and therapy related recovery in cooperative hand movement capacity in stroke patients.

Keywords: activitites of daily living, clinical assessment, cooperative hand movements, reliability, stroke

Procedia PDF Downloads 319
62 Molecular Characterization of Listeria monocytogenes from Fresh Fish and Fish Products

Authors: Beata Lachtara, Renata Szewczyk, Katarzyna Bielinska, Kinga Wieczorek, Jacek Osek

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Listeria monocytogenes is an important human and animal pathogen that causes foodborne outbreaks. The bacteria may be present in different types of food: cheese, raw vegetables, sliced meat products and vacuum-packed sausages, poultry, meat, fish. The most common method, which has been used for the investigation of genetic diversity of L. monocytogenes, is PFGE. This technique is reliable and reproducible and established as gold standard for typing of L. monocytogenes. The aim of the study was characterization by molecular serotyping and PFGE analysis of L. monocytogenes strains isolated from fresh fish and fish products in Poland. A total of 301 samples, including fresh fish (n = 129) and fish products (n = 172) were, collected between January 2014 and March 2016. The bacteria were detected using the ISO 11290-1 standard method. Molecular serotyping was performed with PCR. The isolates were tested with the PFGE method according to the protocol developed by the European Union Reference Laboratory for L. monocytogenes with some modifications. Based on the PFGE profiles, two dendrograms were generated for strains digested separately with two restriction enzymes: AscI and ApaI. Analysis of the fingerprint profiles was performed using Bionumerics software version 6.6 (Applied Maths, Belgium). The 95% of similarity was applied to differentiate the PFGE pulsotypes. The study revealed that 57 of 301 (18.9%) samples were positive for L. monocytogenes. The bacteria were identified in 29 (50.9%) ready-to-eat fish products and in 28 (49.1%) fresh fish. It was found that 40 (70.2%) strains were of serotype 1/2a, 14 (24.6%) 1/2b, two (4.3%) 4b and one (1.8%) 1/2c. Serotypes 1/2a, 1/2b, and 4b were presented with the same frequency in both categories of food, whereas serotype 1/2c was detected only in fresh fish. The PFGE analysis with AscI demonstrated 43 different pulsotypes; among them 33 (76.7%) were represented by only one strain. The remaining 10 profiles contained more than one isolate. Among them 8 pulsotypes comprised of two L. monocytogenes isolates, one profile of three isolates and one restriction type of 5 strains. In case of ApaI typing, the PFGE analysis showed 27 different pulsotypes including 17 (63.0%) types represented by only one strain. Ten (37.0%) clusters contained more than one strain among which four profiles covered two strains; three had three isolates, one with five strains, one with eight strains and one with ten isolates. It was observed that the isolates assigned to the same PFGE type were usually of the same serotype (1/2a or 1/2b). The majority of the clusters had strains of both sources (fresh fish and fish products) isolated at different time. Most of the strains grouped in one cluster of the AscI restriction was assigned to the same groups in ApaI investigation. In conclusion, PFGE used in the study showed a high genetic diversity among L. monocytogenes. The strains were grouped into varied clonal clusters, which may suggest different sources of contamination. The results demonstrated that 1/2a serotype was the most common among isolates from fresh fish and fish products in Poland.

Keywords: Listeria monocytogenes, molecular characteristic, PFGE, serotyping

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61 Prediction of Outcome after Endovascular Thrombectomy for Anterior and Posterior Ischemic Stroke: ASPECTS on CT

Authors: Angela T. H. Kwan, Wenjun Liang, Jack Wellington, Mohammad Mofatteh, Thanh N. Nguyen, Pingzhong Fu, Juanmei Chen, Zile Yan, Weijuan Wu, Yongting Zhou, Shuiquan Yang, Sijie Zhou, Yimin Chen

Abstract:

Background: Endovascular Therapy (EVT)—in the form of mechanical thrombectomy—following intravenous thrombolysis is the standard gold treatment for patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO). It is well established that an ASPECTS ≥ 7 is associated with an increased likelihood of positive post-EVT outcomes, as compared to an ASPECTS < 7. There is also prognostic utility in coupling posterior circulation ASPECTS (pc-ASPECTS) with magnetic resonance imaging for evaluating the post-EVT functional outcome. However, the value of pc-ASPECTS applied to CT must be explored further to determine its usefulness in predicting functional outcomes following EVT. Objective: In this study, we aimed to determine whether pc-ASPECTS on CT can predict post-EVT functional outcomes among patients with AIS due to LVO. Methods: A total of 247 consecutive patients aged 18 and over receiving EVT for LVO-related AIS were recruited into a prospective database. The data were retrospectively analyzed between March 2019 to February 2022 from two comprehensive tertiary care stroke centers: Foshan Sanshui District People’s Hospital and First People's Hospital of Foshan in China. Patient parameters included EVT within 24hrs of symptom onset, premorbid modified Rankin Scale (mRS) ≤ 2, presence of distal and terminal cerebral blood vessel occlusion, and subsequent 24–72-hour post-stroke onset CT scan. Univariate comparisons were performed using the Fisher exact test or χ2 test for categorical variables and the Mann–Whitney U test for continuous variables. A p-value of ≤ 0.05 was statistically significant. Results: A total of 247 patients met the inclusion criteria; however, 3 were excluded due to the absence of post-CTs and 8 for pre-EVT ASPECTS < 7. Overall, 236 individuals were examined: 196 anterior circulation ischemic strokes and 40 posterior strokes of basilar artery occlusion. We found that both baseline post- and pc-ASPECTS ≥ 7 serve as strong positive markers of favorable outcomes at 90 days post-EVT. Moreover, lower rates of inpatient mortality/hospice discharge, 90-day mortality, and 90-day poor outcome were observed. Moreover, patients in the post-ASPECTS ≥ 7 anterior circulation group had shorter door-to-recanalization time (DRT), puncture-to-recanalization time (PRT), and last known normal-to-puncture-time (LKNPT). Conclusion: Patients of anterior and posterior circulation ischemic strokes with baseline post- and pc-ASPECTS ≥ 7 may benefit from EVT.

Keywords: endovascular therapy, thrombectomy, large vessel occlusion, cerebral ischemic stroke, ASPECTS

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60 Assessment of Serum Osteopontin, Osteoprotegerin and Bone-Specific Alp as Markers of Bone Turnover in Patients with Disorders of Thyroid Function in Nigeria, Sub-Saharan Africa

Authors: Oluwabori Emmanuel Olukoyejo, Ogra Victor Ogra, Bosede Amodu, Tewogbade Adeoye Adedeji

Abstract:

Background: Disorders of thyroid function are the second most common endocrine disorders worldwide, with a direct relationship with metabolic bone diseases. These metabolic bone complications are often subtle but manifest as bone pains and an increased risk of fractures. The gold standard for diagnosis, Dual Energy X-ray Absorptiometry (DEXA), is limited in this environment due to unavailability, cumbersomeness and cost. However, bone biomarkers have shown prospects in assessing alterations in bone remodeling, which has not been studied in this environment. Aim: This study evaluates serum levels of bone-specific alkaline phosphatase (bone-specific ALP), osteopontin and osteoprotegerin biomarkers of bone turnover in patients with disorders of thyroid function. Methods: This is a cross-sectional study carried out over a period of one and a half years. Forty patients with thyroid dysfunctions, aged 20 to 50 years, and thirty-eight age and sex-matched healthy euthyroid controls were included in this study. Patients were further stratified into hyperthyroid and hypothyroid groups. Bone-specific ALP, osteopontin, and osteoprotegerin, alongside serum total calcium, ionized calcium and inorganic phosphate, were assayed for all patients and controls. A self-administered questionnaire was used to obtain data on sociodemographic and medical history. Then, 5 ml of blood was collected in a plain bottle and serum was harvested following clotting and centrifugation. Serum samples were assayed for B-ALP, osteopontin, and osteoprotegerin using the ELISA technique. Total calcium and ionized calcium were assayed using an ion-selective electrode, while the inorganic phosphate was assayed with automated photometry. Results: The hyperthyroid and hypothyroid patient groups had significantly increased median serum B-ALP (30.40 and 26.50) ng/ml and significantly lower median OPG (0.80 and 0.80) ng/ml than the controls (10.81 and 1.30) ng/ml respectively, p < 0.05. However, serum osteopontin in the hyperthyroid group was significantly higher and significantly lower in the hypothyroid group when compared with the controls (11.00 and 2.10 vs 3.70) ng/ml, respectively, p < 0.05. Both hyperthyroid and hypothyroid groups had significantly higher mean serum total calcium, ionized calcium and inorganic phosphate than the controls (2.49 ± 0.28, 1.27 ± 0.14 and 1.33 ± 0.33) mmol/l and (2.41 ± 0.04, 1.20 ± 0.04 and 1.15 ± 0.16) mmol/l vs (2.27 ± 0.11, 1.17 ± 0.06 and 1.08 ± 0.16) mmol/l respectively, p < 0.05. Conclusion: Patients with disorders of thyroid function have metabolic imbalances of all the studied bone markers, suggesting a higher bone turnover. The routine bone markers will be an invaluable tool for monitoring bone health in patients with thyroid dysfunctions, while the less readily available markers can be introduced as supplementary tools. Moreover, bone-specific ALP, osteopontin and osteoprotegerin were found to be the strongest independent predictors of metabolic bone markers’ derangements in patients with thyroid dysfunctions.

Keywords: metabolic bone diseases, biomarker, bone turnover, hyperthyroid, hypothyroid, euthyroid

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59 Generating a Multiplex Sensing Platform for the Accurate Diagnosis of Sepsis

Authors: N. Demertzis, J. L. Bowen

Abstract:

Sepsis is a complex and rapidly evolving condition, resulting from uncontrolled prolonged activation of host immune system due to pathogenic insult. The aim of this study is the development of a multiplex electrochemical sensing platform, capable of detecting both pathogen associated and host immune markers to enable the rapid and definitive diagnosis of sepsis. A combination of aptamers and molecular imprinting approaches have been employed to generate sensing systems for lipopolysaccharide (LPS), c-reactive protein (CRP) and procalcitonin (PCT). Gold working electrodes were mechanically polished and electrochemically cleaned with 0.1 M sulphuric acid using cyclic voltammetry (CV). Following activation, a self-assembled monolayer (SAM) was generated, by incubating the electrodes with a thiolated anti-LPS aptamer / dithiodibutiric acid (DTBA) mixture (1:20). 3-aminophenylboronic acid (3-APBA) in combination with the anti-LPS aptamer was used for the development of the hybrid molecularly imprinted sensor (apta-MIP). Aptasensors, targeting PCT and CRP were also fabricated, following the same approach as in the case of LPS, with mercaptohexanol (MCH) replacing DTBA. In the case of the CRP aptasensor, the SAM was formed following incubation of a 1:1 aptamer: MCH mixture. However, in the case of PCT, the SAM was formed with the aptamer itself, with subsequent backfilling with 1 μM MCH. The binding performance of all systems has been evaluated using electrochemical impedance spectroscopy. The apta-MIP’s polymer thickness is controlled by varying the number of electropolymerisation cycles. In the ideal number of polymerisation cycles, the polymer must cover the electrode surface and create a binding pocket around LPS and its aptamer binding site. Less polymerisation cycles will create a hybrid system which resembles an aptasensor, while more cycles will be able to cover the complex and demonstrate a bulk polymer-like behaviour. Both aptasensor and apta-MIP were challenged with LPS and compared to conventional imprinted (absence of aptamer from the binding site, polymer formed in presence of LPS) and non-imprinted polymers (NIPS, absence of LPS whilst hybrid polymer is formed). A stable LPS aptasensor, capable of detecting down to 5 pg/ml of LPS was generated. The apparent Kd of the system was estimated at 17 pM, with a Bmax of approximately 50 pM. The aptasensor demonstrated high specificity to LPS. The apta-MIP demonstrated superior recognition properties with a limit of detection of 1 fg/ml and a Bmax of 100 pg/ml. The CRP and PCT aptasensors were both able to detect down to 5 pg/ml. Whilst full binding performance is currently being evaluated, there is none of the sensors demonstrate cross-reactivity towards LPS, CRP or PCT. In conclusion, stable aptasensors capable of detecting LPS, PCT and CRP at low concentrations have been generated. The realisation of a multiplex panel such as described herein, will effectively contribute to the rapid, personalised diagnosis of sepsis.

Keywords: aptamer, electrochemical impedance spectroscopy, molecularly imprinted polymers, sepsis

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58 Skull Extraction for Quantification of Brain Volume in Magnetic Resonance Imaging of Multiple Sclerosis Patients

Authors: Marcela De Oliveira, Marina P. Da Silva, Fernando C. G. Da Rocha, Jorge M. Santos, Jaime S. Cardoso, Paulo N. Lisboa-Filho

Abstract:

Multiple Sclerosis (MS) is an immune-mediated disease of the central nervous system characterized by neurodegeneration, inflammation, demyelination, and axonal loss. Magnetic resonance imaging (MRI), due to the richness in the information details provided, is the gold standard exam for diagnosis and follow-up of neurodegenerative diseases, such as MS. Brain atrophy, the gradual loss of brain volume, is quite extensive in multiple sclerosis, nearly 0.5-1.35% per year, far off the limits of normal aging. Thus, the brain volume quantification becomes an essential task for future analysis of the occurrence atrophy. The analysis of MRI has become a tedious and complex task for clinicians, who have to manually extract important information. This manual analysis is prone to errors and is time consuming due to various intra- and inter-operator variability. Nowadays, computerized methods for MRI segmentation have been extensively used to assist doctors in quantitative analyzes for disease diagnosis and monitoring. Thus, the purpose of this work was to evaluate the brain volume in MRI of MS patients. We used MRI scans with 30 slices of the five patients diagnosed with multiple sclerosis according to the McDonald criteria. The computational methods for the analysis of images were carried out in two steps: segmentation of the brain and brain volume quantification. The first image processing step was to perform brain extraction by skull stripping from the original image. In the skull stripper for MRI images of the brain, the algorithm registers a grayscale atlas image to the grayscale patient image. The associated brain mask is propagated using the registration transformation. Then this mask is eroded and used for a refined brain extraction based on level-sets (edge of the brain-skull border with dedicated expansion, curvature, and advection terms). In the second step, the brain volume quantification was performed by counting the voxels belonging to the segmentation mask and converted in cc. We observed an average brain volume of 1469.5 cc. We concluded that the automatic method applied in this work can be used for the brain extraction process and brain volume quantification in MRI. The development and use of computer programs can contribute to assist health professionals in the diagnosis and monitoring of patients with neurodegenerative diseases. In future works, we expect to implement more automated methods for the assessment of cerebral atrophy and brain lesions quantification, including machine-learning approaches. Acknowledgements: This work was supported by a grant from Brazilian agency Fundação de Amparo à Pesquisa do Estado de São Paulo (number 2019/16362-5).

Keywords: brain volume, magnetic resonance imaging, multiple sclerosis, skull stripper

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57 Rt-Pcr Negative COVID-19 Infection in a Bodybuilding Competitor Using Anabolic Steroids: A Case Report

Authors: Mariana Branco, Nahida Sobrino, Cristina Neves, Márcia Santos, Afonso Granja, João Rosa Oliveira, Joana Costa, Luísa Castro Leite

Abstract:

This case reports a COVID-19 infection in an unvaccinated adult man with no history of COVID-19 and no relevant clinical history besides anabolic steroid use, undergoing weaning with tamoxifen after a bodybuilding competition. The patient presented a 4cm cervical mass 3 weeks after COVID-19 infection in his cohabitants. He was otherwise asymptomatic and tested negative to multiple RT-PCR tests. Nevertheless, the IgG COVID-19 antibody was positive, suggesting the previous infection. This report raises a potential link between anabolic steroid use and atypical COVID-19 onset. Objectives: The goals of this paper are to raise a potential link between anabolic steroid use and atypical COVID-19 onset but also to report an uncommon case of COVID-19 infection with consecutive negative gold standard tests. Methodology: The authors used CARE guidelines for case report writing. Introduction: This case reports a COVID-19 infection case in an unvaccinated adult man, with multiple serial negative reverse transcription polymerase chain reaction (RT-PCR) test results, presenting with single cervical lymphadenopathy. Although the association between COVID-19 and lymphadenopathy is well established, there are no cases with this presentation, and consistently negative RT-PCR tests have been reported. Methodologies: The authors used CARE guidelines for case report writing. Case presentation: This case reports a 28-year-old Caucasian man with no previous history of COVID-19 infection or vaccination and no relevant clinical history besides anabolic steroid use undergoing weaning with tamoxifendue to participation in a bodybuilding competition. He visits his primary care physician because of a large (4 cm) cervical lump, present for 3 days prior to the consultation. There was a positive family history for COVID-19 infection 3 weeks prior to the visit, during which the patient cohabited with the infected family members. The patient never had any previous clinical manifestation of COVID-19 infection and, despite multiple consecutive RT-PCR testing, never tested positive. The patient was treated with an NSAID and a broad-spectrum antibiotic, with little to no effect. Imagiological testing was performed via a cervical ultrasound, followed by a needle biopsy for histologic analysis. Serologic testing for COVID-19 immunity was conducted, revealing a positive Anti-SARS-CoV-2 IgG (Spike S1) antibody, suggesting the previous infection, given the unvaccinated status of our patient Conclusion: In patients with a positive epidemiologic context and cervical lymphadenopathy, physicians should still consider COVID-19 infection as a differential diagnosis, despite negative PCR testing. This case also raises a potential link between anabolic steroid use and atypical COVID-19 onset, never before reported in scientific literature.

Keywords: COVID-19, cervical lymphadenopathy, anabolic steroids, primary care

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56 Dynamic-cognition of Strategic Mineral Commodities; An Empirical Assessment

Authors: Carlos Tapia Cortez, Serkan Saydam, Jeff Coulton, Claude Sammut

Abstract:

Strategic mineral commodities (SMC) both energetic and metals have long been fundamental for human beings. There is a strong and long-run relation between the mineral resources industry and society's evolution, with the provision of primary raw materials, becoming one of the most significant drivers of economic growth. Due to mineral resources’ relevance for the entire economy and society, an understanding of the SMC market behaviour to simulate price fluctuations has become crucial for governments and firms. For any human activity, SMC price fluctuations are affected by economic, geopolitical, environmental, technological and psychological issues, where cognition has a major role. Cognition is defined as the capacity to store information in memory, processing and decision making for problem-solving or human adaptation. Thus, it has a significant role in those systems that exhibit dynamic equilibrium through time, such as economic growth. Cognition allows not only understanding past behaviours and trends in SCM markets but also supports future expectations of demand/supply levels and prices, although speculations are unavoidable. Technological developments may also be defined as a cognitive system. Since the Industrial Revolution, technological developments have had a significant influence on SMC production costs and prices, likewise allowing co-integration between commodities and market locations. It suggests a close relation between structural breaks, technology and prices evolution. SCM prices forecasting have been commonly addressed by econometrics and Gaussian-probabilistic models. Econometrics models may incorporate the relationship between variables; however, they are statics that leads to an incomplete approach of prices evolution through time. Gaussian-probabilistic models may evolve through time; however, price fluctuations are addressed by the assumption of random behaviour and normal distribution which seems to be far from the real behaviour of both market and prices. Random fluctuation ignores the evolution of market events and the technical and temporal relation between variables, giving the illusion of controlled future events. Normal distribution underestimates price fluctuations by using restricted ranges, curtailing decisions making into a pre-established space. A proper understanding of SMC's price dynamics taking into account the historical-cognitive relation between economic, technological and psychological factors over time is fundamental in attempting to simulate prices. The aim of this paper is to discuss the SMC market cognition hypothesis and empirically demonstrate its dynamic-cognitive capacity. Three of the largest and traded SMC's: oil, copper and gold, will be assessed to examine the economic, technological and psychological cognition respectively.

Keywords: commodity price simulation, commodity price uncertainties, dynamic-cognition, dynamic systems

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55 Integration of a Protective Film to Enhance the Longevity and Performance of Miniaturized Ion Sensors

Authors: Antonio Ruiz Gonzalez, Kwang-Leong Choy

Abstract:

The measurement of electrolytes has a high value in the clinical routine. Ions are present in all body fluids with variable concentrations and are involved in multiple pathologies such as heart failures and chronic kidney disease. In the case of dissolved potassium, although a high concentration in the blood (hyperkalemia) is relatively uncommon in the general population, it is one of the most frequent acute electrolyte abnormalities. In recent years, the integration of thin films technologies in this field has allowed the development of highly sensitive biosensors with ultra-low limits of detection for the assessment of metals in liquid samples. However, despite the current efforts in the miniaturization of sensitive devices and their integration into portable systems, only a limited number of successful examples used commercially can be found. This fact can be attributed to a high cost involved in their production and the sustained degradation of the electrodes over time, which causes a signal drift in the measurements. Thus, there is an unmet necessity for the development of low-cost and robust sensors for the real-time monitoring of analyte concentrations in patients to allow the early detection and diagnosis of diseases. This paper reports a thin film ion-selective sensor for the evaluation of potassium ions in aqueous samples. As an alternative for this fabrication method, aerosol assisted chemical vapor deposition (AACVD), was applied due to cost-effectivity and fine control over the film deposition. Such a technique does not require vacuum and is suitable for the coating of large surface areas and structures with complex geometries. This approach allowed the fabrication of highly homogeneous surfaces with well-defined microstructures onto 50 nm thin gold layers. The degradative processes of the ubiquitously employed poly (vinyl chloride) membranes in contact with an electrolyte solution were studied, including the polymer leaching process, mechanical desorption of nanoparticles and chemical degradation over time. Rational design of a protective coating based on an organosilicon material in combination with cellulose to improve the long-term stability of the sensors was then carried out, showing an improvement in the performance after 5 weeks. The antifouling properties of such coating were assessed using a cutting-edge quartz microbalance sensor, allowing the quantification of the adsorbed proteins in the nanogram range. A correlation between the microstructural properties of the films with the surface energy and biomolecules adhesion was then found and used to optimize the protective film.

Keywords: hyperkalemia, drift, AACVD, organosilicon

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54 Effect of Ti, Nb, and Zr Additives on Biocompatibility of Injection Molded 316L Stainless Steel for Biomedical Applications

Authors: Busra Gundede, Ozal Mutlu, Nagihan Gulsoy

Abstract:

Background: Over the years, material research has led to the development of numerous metals and alloys for using in biomedical applications. One of the major tasks of biomaterial research is the functionalization of the material surface to improve the biocompatibility according to a specific application. 316L and 316L alloys are excellent for various bio-applications. This research was investigated the effect of titanium (Ti), niobium (Nb), and zirconium (Zr) additives on injection molded austenitic grade 316L stainless steels in vitro biocompatibility. For this purpose, cytotoxic tests were performed to evaluate the potential biocompatibility of the specimens. Materials and Methods: 3T3 fibroblast were cultivated in DMEM supplemented with 10% fetal bovine serum and %1 penicillin-streptomycin at 37°C with 5% CO2 and 95%humidity. Trypsin/EDTA solution was used to remove cells from the culture flask. Cells were reseeded at a density of 1×105cell in 25T flasks. The medium change took place every 3 days. The trypan blue assay was used to determine cell viability. Cell viability is calculated as the number of viable cells divided by the total number of cells within the grids on the cell counter machine counted the number of blue staining cells and the number of total cells. Cell viability should be at least 95% for healthy log-phase cultures. MTT assay was assessed for 96-hours. Cells were cultivated in 6-well flask within 5 ml DMEM and incubated as same conditions. 0,5mg/ml MTT was added for 4-hours and then acid-isoprohanol was added for solubilize to formazan crystals. Cell morphology after 96h was investigated by SEM. The medium was removed, samples were washed with 0.15 M PBS buffer and fixed for 12h at 4- 8°C with %2,5 gluteraldehyte. Samples were treated with 1% osmium tetroxide. Samples were then dehydrated and dried, mounted on appropriate stubs with colloidal silver and sputter-coated with gold. Images were collected using a scanning electron microscope. ROS assay is a cell viability test for in vitro studies. Cells were grown for 96h, ROS solution added on cells in 6 well plate flask and incubated for 1h. Fluorescence signal indicates ROS generation by cells. Results: Trypan Blue exclusion assay results were 96%, 92%, 95%, 90%, 91% for negative control group, 316L, 316L-Ti, 316L-Nb and 316L-Zr, respectively. Results were found nearly similar to each other when compared with control group. Cell viability from MTT analysis was found to be 100%, 108%, 103%, 107%, and 105% for the control group, 316L, 316L-Ti, 316L-Nb and 316L-Zr, respectively. Fluorescence microscopy analysis indicated that all test groups were same as the control group in ROS assay. SEM images demonstrated that the attachment of 3T3 cells on biomaterials. Conclusion: We, therefore, concluded that Ti, Nb and Zr additives improved physical properties of 316L stainless. In our in vitro experiments showed that these new additives did not modify the cytocompatibility of stainless steel and these additives on 316L might be useful for biomedical applications.

Keywords: 316L stainles steel, biocompatibility, cell culture, Ti, Nb, Zr

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53 An Audit of Climate Change and Sustainability Teaching in Medical School

Authors: Karolina Wieczorek, Zofia Przypaśniak

Abstract:

Climate change is a rapidly growing threat to global health, and part of the responsibility to combat it lies within the healthcare sector itself, including adequate education of future medical professionals. To mitigate the consequences, the General Medical Council (GMC) has equipped medical schools with a list of outcomes regarding sustainability teaching. Students are expected to analyze the impact of the healthcare sector’s emissions on climate change. The delivery of the related teaching content is, however, often inadequate and insufficient time is devoted for exploration of the topics. Teaching curricula lack in-depth exploration of the learning objectives. This study aims to assess the extent and characteristics of climate change and sustainability subjects teaching in the curriculum of a chosen UK medical school (Barts and The London School of Medicine and Dentistry). It compares the data to the national average scores from the Climate Change and Sustainability Teaching (C.A.S.T.) in Medical Education Audit to draw conclusions about teaching on a regional level. This is a single-center audit of the timetabled sessions of teaching in the medical course. The study looked at the academic year 2020/2021 which included a review of all non-elective, core curriculum teaching materials including tutorials, lectures, written resources, and assignments in all five years of the undergraduate and graduate degrees, focusing only on mandatory teaching attended by all students (excluding elective modules). The topics covered were crosschecked with GMC Outcomes for graduates: “Educating for Sustainable Healthcare – Priority Learning Outcomes” as gold standard to look for coverage of the outcomes and gaps in teaching. Quantitative data was collected in form of time allocated for teaching as proxy of time spent per individual outcomes. The data was collected independently by two students (KW and ZP) who have received prior training and assessed two separate data sets to increase interrater reliability. In terms of coverage of learning outcomes, 12 out of 13 were taught (with the national average being 9.7). The school ranked sixth in the UK for time spent per topic and second in terms of overall coverage, meaning the school has a broad range of topics taught with some being explored in more detail than others. For the first outcome 4 out of 4 objectives covered (average 3.5) with 47 minutes spent per outcome (average 84 min), for the second objective 5 out of 5 covered (average 3.5) with 46 minutes spent (average 20), for the third 3 out of 4 (average 2.5) with 10 mins pent (average 19 min). A disproportionately large amount of time is spent delivering teaching regarding air pollution (respiratory illnesses), which resulted in the topic of sustainability in other specialties being excluded from teaching (musculoskeletal, ophthalmology, pediatrics, renal). Conclusions: Currently, there is no coherent strategy on national teaching of climate change topics and as a result an unstandardized amount of time spent on teaching and coverage of objectives can be observed.

Keywords: audit, climate change, sustainability, education

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52 Patterns of Change in Specific Behaviors of Autism Symptoms for Boys and for Girls Across Childhood

Authors: Einat Waizbard, Emilio Ferrer, Meghan Miller, Brianna Heath, Derek S. Andrews, Sally J. Rogers, Christine Wu Nordahl, Marjorie Solomon, David G. Amaral

Abstract:

Background: Autism symptoms are comprised of social-communication deficits and restricted/repetitive behaviors (RRB). The severity of these symptoms can change during childhood, with differences between boys and girls. From the literature, it was found that young autistic girls show a stronger tendency to decrease and a weaker tendency to increase their overall autism symptom severity levels compared to young autistic boys. It is not clear, however, which symptoms are driving these sex differences across childhood. In the current study, we evaluated the trajectories of independent autism symptoms across childhood and compared the patterns of change in such symptoms between boys and girls. Method: The study included 183 children diagnosed with autism (55 girls) evaluated three times across childhood, at ages 3, 6 and 11. We analyzed 22 independent items from the Autism Diagnostic Observation Scheudule-2 (ADOS-2), the gold-standard assessment tool for autism symptoms, each item representing a specific autism symptom. First, we used latent growth curve models to estimate the trajectories for the 22 ADOS-2 items for each child in the study. Second, we extracted the factor scores representing the individual slopes for each ADOS-2 item (i.e., slope representing that child’s change in that specific item). Third, we used factor analysis to identify common patterns of change among the ADOS-2 items, separately for boys and girls, i.e., which autism symptoms tend to change together and which change independently across childhood. Results: The best-emerging patterns for both boys and girls identified four common factors: three factors representative of changes in social-communication symptoms and one factor describing changes in RRB. Boys and girls showed the same pattern of change in RRB, with four items (e.g., speech abnormalities) changing together across childhood and three items (e.g., mannerisms) changing independently of other items. For social-communication deficits in boys, three factors were identified: the first factor included six items representing initiating and engaging in social-communication (e.g., quality of social overtures, conversation), the second factor included five items describing responsive social-communication (e.g., response to name) and the third factor included three items related to different aspects of social-communication (e.g., level of language). Girls’ social-communications deficits also loaded onto three factors: the first factor included five items (e.g., unusual eye contact), the second factor included six items (e.g., quality of social response), and the third factor included four items (e.g., showing). Some items showed similar patterns of change for both sexes (e.g., responsive joint attention), while other items showed differences (e.g., shared enjoyment). Conclusions: Girls and boys had different patterns of change in autism symptom severity across childhood. For RRB, both sexes showed similar patterns. For social-communication symptoms, however, there were both similarities and differences between boys and girls in the way symptoms changed over time. The strongest patterns of change were identified for initiating and engaging in social communication for boys and responsive social communication for girls.

Keywords: autism spectrum disorder, autism symptom severity, symptom trajectories, sex differences

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51 Functional Switching of Serratia marcescens Transcriptional Regulator from Activator to Inhibitor of Quorum Sensing by Exogenous Addition

Authors: Norihiro Kato, Yuriko Takayama

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Some gram-negative bacteria enable the simultaneous activation of gene expression involved in N-acylhomoserine lactone (AHL) dependent cell-to-cell communication system. Such regulatory system for the bacterial group behavior is termed as quorum sensing (QS) because a diffusible AHL signal can accumulate around the cell during the increase of the cell density and trigger activation of the sequential QS process. By blocking the QS, the expression of diverse genes related to infection, antibiotic production, and biofilm formation is inhibited. Conditioning of QS by regulation of the DNA-receptor-AHL interaction is a potential target for enhancing host defenses against pathogenicity. We focused on engineered application of transcriptional regulator SpnR produced in opportunistic human pathogen Serratia marcescens. The SpnR can interact with AHL signals at an N-terminal domain and also with a promoter region of a QS target gene at a C-terminal domain. As the initial process of the QS activation, the SpnR forms a complex with the AHL to enhance the expression of pig cluster; the SpnR normally acts as an activator for the expression of the QS-dependent gene. In this research, we attempt to artificially control QS by changing the role of SpnR. The QS-dependent prodigiosin production is expected to inhibit by externally added SpnR in the culture broth of AS-1 strain because the AHL concentration was kept below the threshold by AHL-SpnR complex formation. Maltose-binding protein (MBP)-tagged SpnR (MBP-SpnR) was overexpressed in Escherichia coli and purified using an affinity chromatography equipped with an amylose resin column. The specific interaction between AHL and MBP-SpnR was demonstrated by quartz crystal microbalance (QCM) sensor. AHL with amino end-group was coupled with COOH-terminated self-assembled monolayer prepared on a gold electrode of 27-MHz quartz crystal sensor using water-soluble carbodiimide. After the injection of MBP-SpnR into a cup-type sensor cell filled with the buffer solution, time course of resonant frequency change (ΔFs) was determined. A decrease of ΔFs clearly showed the uptake of MBP-SpnR onto the AHL-immobilized electrode. Furthermore, no binding affinity was observed after the heat-inactivation of MBP-SpnR at 80ºC. These results suggest that MBP-SpnR possesses a specific affinity for AHL. MBP-SpnR was added to the culture medium as an AHL trap to study inhibitory effects on intracellularly accumulated prodigiosin. With approximately 2 µM MBP-SpnR, the amount of prodigiosin induced was half that of the control without any additives. In conclusion, the function of SpnR could be switched by adding it to the cell culture. Exogenously added MBP-SpnR possesses high affinity for AHL derived from cells and acts as an inhibitor of AHL-mediated QS.

Keywords: intracellular signaling, microbial biotechnology, quorum sensing, transcriptional regulator

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50 Preparation of Metallic Nanoparticles with the Use of Reagents of Natural Origin

Authors: Anna Drabczyk, Sonia Kudlacik-Kramarczyk, Dagmara Malina, Bozena Tyliszczak, Agnieszka Sobczak-Kupiec

Abstract:

Nowadays, nano-size materials are very popular group of materials among scientists. What is more, these materials find an application in a wide range of various areas. Therefore constantly increasing demand for nanomaterials including metallic nanoparticles such as silver of gold ones is observed. Therefore, new routes of their preparation are sought. Considering potential application of nanoparticles, it is important to select an adequate methodology of their preparation because it determines their size and shape. Among the most commonly applied methods of preparation of nanoparticles chemical and electrochemical techniques are leading. However, currently growing attention is directed into the biological or biochemical aspects of syntheses of metallic nanoparticles. This is associated with a trend of developing of new routes of preparation of given compounds according to the principles of green chemistry. These principles involve e.g. the reduction of the use of toxic compounds in the synthesis as well as the reduction of the energy demand or minimization of the generated waste. As a result, a growing popularity of the use of such components as natural plant extracts, infusions or essential oils is observed. Such natural substances may be used both as a reducing agent of metal ions and as a stabilizing agent of formed nanoparticles therefore they can replace synthetic compounds previously used for the reduction of metal ions or for the stabilization of obtained nanoparticles suspension. Methods that proceed in the presence of previously mentioned natural compounds are environmentally friendly and proceed without the application of any toxic reagents. Methodology: Presented research involves preparation of silver nanoparticles using selected plant extracts, e.g. artichoke extract. Extracts of natural origin were used as reducing and stabilizing agents at the same time. Furthermore, syntheses were carried out in the presence of additional polymeric stabilizing agent. Next, such features of obtained suspensions of nanoparticles as total antioxidant activity as well as content of phenolic compounds have been characterized. First of the mentioned studies involved the reaction with DPPH (2,2-Diphenyl-1-picrylhydrazyl) radical. The content of phenolic compounds was determined using Folin-Ciocalteu technique. Furthermore, an essential issue was also the determining of the stability of formed suspensions of nanoparticles. Conclusions: In the research it was demonstrated that metallic nanoparticles may be obtained using plant extracts or infusions as stabilizing or reducing agent. The methodology applied, i.e. a type of plant extract used during the synthesis, had an impact on the content of phenolic compounds as well as on the size and polydispersity of obtained nanoparticles. What is more, it is possible to prepare nano-size particles that will be characterized by properties desirable from the viewpoint of their potential application and such an effect may be achieved with the use of non-toxic reagents of natural origin. Furthermore, proposed methodology stays in line with the principles of green chemistry.

Keywords: green chemistry principles, metallic nanoparticles, plant extracts, stabilization of nanoparticles

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49 Engineered Control of Bacterial Cell-to-Cell Signaling Using Cyclodextrin

Authors: Yuriko Takayama, Norihiro Kato

Abstract:

Quorum sensing (QS) is a cell-to-cell communication system in bacteria to regulate expression of target genes. In gram-negative bacteria, activation on QS is controlled by a concentration increase of N-acylhomoserine lactone (AHL), which can diffuse in and out of the cell. Effective control of QS is expected to avoid virulence factor production in infectious pathogens, biofilm formation, and antibiotic production because various cell functions in gram-negative bacteria are controlled by AHL-mediated QS. In this research, we applied cyclodextrins (CDs) as artificial hosts for the AHL signal to reduce the AHL concentration in the culture broth below its threshold for QS activation. The AHL-receptor complex induced under the high AHL concentration activates transcription of the QS-target gene. Accordingly, artificial reduction of the AHL concentration is one of the effective strategies to inhibit the QS. A hydrophobic cavity of the CD can interact with the acyl-chain of the AHL due to hydrophobic interaction in aqueous media. We studied N-hexanoylhomoserine lactone (C6HSL)-mediated QS in Serratia marcescens; accumulation of C6HSL is responsible for regulation of the expression of pig cluster. Inhibitory effects of added CDs on QS were demonstrated by determination of prodigiosin amount inside cells after reaching stationary phase, because production of prodigiosin depends on the C6HSL-mediated QS. By adding approximately 6 wt% hydroxypropyl-β-CD (HP-β-CD) in Luria-Bertani (LB) medium prior to inoculation of S. maecescens AS-1, the intracellularly accumulated prodigiosin was drastically reduced to 7-10%, which was determined after the extraction of prodigiosin in acidified ethanol. The AHL retention ability of HP-β-CD was also demonstrated by Chromobacterium violacuem CV026 bioassay. The CV026 strain is an AHL-synthase defective mutant that activates QS solely by adding AHLs from outside of cells. A purple pigment violacein is induced by activation of the AHL-mediated QS. We demonstrated that the violacein production was effectively suppressed when the C6HSL standard solution was spotted on a LB agar plate dispersing CV026 cells and HP-β-CD. Physico-chemical analysis was performed to study the affinity between the immobilized CD and added C6HSL using a quartz crystal microbalance (QCM) sensor. The COOH-terminated self-assembled monolayer was prepared on a gold electrode of 27-MHz AT-cut quartz crystal. Mono(6-deoxy-6-N, N-diethylamino)-β-CD was immobilized on the electrode using water-soluble carbodiimide. The C6HSL interaction with the β-CD cavity was studied by injecting the C6HSL solution to a cup-type sensor cell filled with buffer solution. A decrement of resonant frequency (ΔFs) clearly showed the effective C6HSL complexation with immobilized β-CD and its stability constant for MBP-SpnR-C6HSL complex was on the order of 102 M-1. The CD has high potential for engineered control of QS because it is safe for human use.

Keywords: acylhomoserine lactone, cyclodextrin, intracellular signaling, quorum sensing

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48 Assessing the High Rate of Deforestation Caused by the Operations of Timber Industries in Ghana

Authors: Obed Asamoah

Abstract:

Forests are very vital for human survival and our well-being. During the past years, the world has taken an increasingly significant role in the modification of the global environment. The high rate of deforestation in Ghana is of primary national concern as the forests provide many ecosystem services and functions that support the country’s predominantly agrarian economy and foreign earnings. Ghana forest is currently major source of carbon sink that helps to mitigate climate change. Ghana forests, both the reserves and off-reserves, are under pressure of deforestation. The causes of deforestation are varied but can broadly be categorized into anthropogenic and natural factors. For the anthropogenic factors, increased wood fuel collection, clearing of forests for agriculture, illegal and poorly regulated timber extraction, social and environmental conflicts, increasing urbanization and industrialization are the primary known causes for the loss of forests and woodlands. Mineral exploitation in the forest areas is considered as one of the major causes of deforestation in Ghana. Mining activities especially mining of gold by both the licensed mining companies and illegal mining groups who are locally known as "gallantly mining" also cause damage to the nation's forest reserves. Several works have been conducted regarding the causes of the high rate of deforestation in Ghana, major attention has been placed on illegal logging and using forest lands for illegal farming and mining activities. Less emphasis has been placed on the timber production companies on their harvesting methods in the forests in Ghana and other activities that are carried out in the forest. The main objective of the work is to find out the harvesting methods and the activities of the timber production companies and their effects on the forests in Ghana. Both qualitative and quantitative research methods were engaged in the research work. The study population comprised of 20 Timber industries (Sawmills) forest areas of Ghana. These companies were selected randomly. The cluster sampling technique was engaged in selecting the respondents. Both primary and secondary data were employed. In the study, it was observed that most of the timber production companies do not know the age, the weight, the distance covered from the harvesting to the loading site in the forest. It was also observed that old and heavy machines are used by timber production companies in their operations in the forest, which makes the soil compact prevents regeneration and enhances soil erosion. It was observed that timber production companies do not abide by the rules and regulations governing their operations in the forest. The high rate of corruption on the side of the officials of the Ghana forestry commission makes the officials relax and do not embark on proper monitoring on the operations of the timber production companies which makes the timber companies to cause more harm to the forest. In other to curb this situation the Ghana forestry commission with the ministry of lands and natural resources should monitor the activities of the timber production companies and sanction all the companies that make foul play in their activities in the forest. The commission should also pay more attention to the policy “fell one plant 10” to enhance regeneration in both reserves and off-reserves forest.

Keywords: companies, deforestation, forest, Ghana, timber

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47 Study Protocol: Impact of a Sustained Health Promoting Workplace on Stock Price Performance and Beta - A Singapore Case

Authors: Wee Tong Liaw, Elaine Wong Yee Sing

Abstract:

Since 2001, many companies in Singapore have voluntarily participated in the bi-annual Singapore HEALTH Award initiated by the Health Promotion Board of Singapore (HPB). The Singapore HEALTH Award (SHA), is an industry wide award and assessment process. SHA assesses and recognizes employers in Singapore for implementing a comprehensive and sustainable health promotion programme at their workplaces. The rationale for implementing a sustained health promoting workplace and participating in SHA is obvious when company management is convinced that healthier employees, business productivity, and profitability are positively correlated. However, performing research or empirical studies on the impact of a sustained health promoting workplace on stock returns are not likely to yield any interests in the absence of a systematic and independent assessment on the comprehensiveness and sustainability of a health promoting workplace in most developed economies. The principles of diversification and mean-variance efficient portfolio in Modern Portfolio Theory developed by Markowitz (1952) laid the foundation for the works of many financial economists and researchers, and among others, the development of the Capital Asset Pricing Model from the work of Sharpe (1964), Lintner (1965) and Mossin (1966), and the Fama-French Three-Factor Model of Fama and French (1992). This research seeks to support the rationale by studying whether there is a significant relationship or impact of a sustained health promoting workplace on the performance of companies listed on the SGX. The research shall form and test hypotheses pertaining to the impact of a sustained health promoting workplace on company’s performances, including stock returns, of companies that participated in the SHA and companies that did not participate in the SHA. In doing so, the research would be able to determine whether corporate and fund manager should consider the significance of a sustained health promoting workplace as a risk factor to explain the stock returns of companies listed on the SGX. With respect to Singapore’s stock market, this research will test the significance and relevance of a health promoting workplace using the Singapore Health Award as a proxy for non-diversifiable risk factor to explain stock returns. This study will examine the significance of a health promoting workplace on a company’s performance and study its impact on stock price performance and beta and examine if it has higher explanatory power than the traditional single factor asset pricing model CAPM (Capital Asset Pricing Model). To study the significance there are three key questions pertinent to the research study. I) Given a choice, would an investor be better off investing in a listed company with a sustained health promoting workplace i.e. a Singapore Health Award’s recipient? II) The Singapore Health Award has four levels of award starting from Bronze, Silver, Gold to Platinum. Would an investor be indifferent to the level of award when investing in a listed company who is a Singapore Health Award’s recipient? III) Would an asset pricing model combining FAMA-French Three Factor Model and ‘Singapore Health Award’ factor be more accurate than single factor Capital Asset Pricing Model and the Three Factor Model itself?

Keywords: asset pricing model, company's performance, stock prices, sustained health promoting workplace

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46 Abnormal Pap Smear Detection by Application of Revised Bethesda System in Commercial Sex Workers and a Control Group: A Comparative Study

Authors: Priyanka Manghani, Manthan Patel, Rahul Peddawad

Abstract:

Cervical Cancer is a major public health hurdle in the area of women’s health. The most common cause of Cervical Cancer is the Human Papilloma Virus (HPV). Human papilloma virus has various genotypes, with HPV 16 and HPV 18 being the major etiological factor causing carcinoma of the Cervix. Early screening and detection by Papanicolaou Smears (PAP) is an effective method for identifying premalignant and malignant lesions. In case of existing pre- malignant lesions /cervical dysplasia’s found with HPV 16 or 18, appropriate follow up can be done to prevent it from developing into a neoplasm. Aims and Objectives: Primary Aim; To study various abnormal cervical cytology reports as detected by Pap Smear Tests, using the Bethesda System in women at a Tertiary Care Hospital. Secondary Aim; To discuss the importance of Pap smear in Cervical Cancer Screening Program. Materials and Methods: Our study is a prospective study, based on 101 women who attended the Out-patient department of Obstetrics and Gynecology at a tertiary care hospital in age group 20-40 years with chief complaints of white/foul vaginal discharge, post-coital Bleeding, low back pain, irregular menstruation, etc. 60 women, who were tested, of the total no of women, were commercial sex workers, thus being a high-risk group for HPV infection. All women underwent conventional cytology. For all the abnormal smears, further cervical biopsies were done, and the final diagnosis was done on the basis of histopathology (gold standard). Results: In all these patients, 16 patients presented with normal smears out of which 2 belonged to the category of commercial sex workers (3.33%) and 14 being from the normal/control group (34.15%). 44 women presented with inflammatory smears out of which 30 were commercial sex workers (50%) and 14 from the control Group (34.15%). A total of 11 women presented with infectious etiology with 6 being commercial sex workers (10%) and 5 (12.2%) being in the control group. A total of 8 patients presented with low-grade squamous intra epithelial lesion (LSIL) with 7 (11.7%) being commercial sex workers and 1(2.44%) patient belonging to the control group. A Total of 7 patients presented with high-grade squamous intraepithelial lesion (HSIL) with 6 (10%) being commercial sex workers and 1 (2.44%) belonging to the control group. 9 patients in total presented with atypical squamous cells of undetermined significance (ASCUS) with 6(10%) being commercial sex workers and 3 (7.32%) belonging to the control group. Squamous cell carcinoma(SCC) presence was found only in 1(1.7%) commercial sex worker. Conclusion – We conclude that HSIL, LSIL, SCC and sexually related infections are comparatively more common in vulnerable groups such as sex workers due to a variety of factors such as multiple sexual partners and poor genital hygiene. Early screening and follow up interventions are highly needed for them along with Health education for risk factors and to emphasize on the importance of Pap smear screening.

Keywords: cervical cancer, papanicolaou (pap) smear, bethesda system, neoplasm

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45 Evaluating Therapeutic Efficacy of Intravesical Xenogeneic Urothelial Cell Treatment Alone and in Combination with Chemotherapy or Immune Checkpoint Inhibitors in a Mouse Non-Muscle-Invasive Bladder Cancer Model

Authors: Chih-Rong Shyr, Chi-Ping Huang

Abstract:

Intravesical BCG is the gold-standard therapy for high risk non-muscle invasive bladder cancer (NMIBC) after TURBT, but if not responsive to BCG, these BCG unresponsive patients face cystectomy that causes morbidity and comes with a morality risk. To provide the bladder sparing options for patients with BCG-unresponsive NMIBC, several new treatments have been developed to salvage the bladders and prevent progression to muscle invasive or metastatic, but however, most approved or developed treatments still fail in a significant proportion of patients without long term success. Thus more treatment options and the combination of different therapeutic modalities are urgently needed to change the outcomes. Xenogeneic rejection has been proposed to a mechanism of action to induce anti-tumor immunity for the treatment of cancers due to the similarities between rejection mechanism to xenoantigens (proteins, glycans and lipids) and anti-tumor immunities to tumor specific antigens (neoantigens, tumor associated carbohydrates and lipids). Xenogeneic urothelial cells (XUC) of porcine origin have been shown to induce anti-tumor immune responses to inhibit bladder tumor progression in mouse bladder cancer models. To further demonstrate the efficacy of the distinct intravesical XUC treatment in NMIBC, and the combined effects with chemotherapy and immune checkpoint inhibitors (ICIs) as a alternate therapeutic option, this study investigated the therapeutic effects and mechanisms of intravesical XUC immunotherapy in an orthotopic mouse immune competent model of NMIBC, generated from a mouse bladder cancer cell line. We found that the tumor progression was inhibited by intravescial XUC treatment and there was a synergy between intravesical XUC with intravesical chemotherapeutic agent, gemcitabine or systemic ICI, anti-PD1 antibody treatment. The cancer cell proliferation was decreased but the cell death was increased by the intravecisal XUC treatment. Most importantly, the mechanisms of action of intravesical XUC immunotherapy were found to be linked to enhanced infiltration of CD4+ and CD8+ T-cell as well as NK cells, but decreased presence of myeloid immunosuppressive cells in XUC treated tumors. The increased stimulation of immune cells of XUC treated mice to xenogeneic urothelial cells and mouse bladder cancer cells in immune cell proliferation and cytokine secretion were observed both as a monotherapy and in combination with intravesical gemcitabine or systemic anti PD-L1 treatment. In sum, we identified the effects of intravesical XUC treatment in monotherapy and combined therapy on tumor progression and its cellular and molecular events related to immune activation to understand the anti-tumoral mechanisms behind intravesical XUC immunotherapy for NMIBC. These results contribute to the understanding of the mechanisms behind successful xenogeneic cell immunotherapy against NMIBC and characterize a novel therapeutic approach with a new xenogeneic cell modality for BCG-unresponsive NMIBC.

Keywords: xenoantigen, neoantigen, rejection, immunity

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44 Cost Based Analysis of Risk Stratification Tool for Prediction and Management of High Risk Choledocholithiasis Patients

Authors: Shreya Saxena

Abstract:

Background: Choledocholithiasis is a common complication of gallstone disease. Risk scoring systems exist to guide the need for further imaging or endoscopy in managing choledocholithiasis. We completed an audit to review the American Society for Gastrointestinal Endoscopy (ASGE) scoring system for prediction and management of choledocholithiasis against the current practice at a tertiary hospital to assess its utility in resource optimisation. We have now conducted a cost focused sub-analysis on patients categorized high-risk for choledocholithiasis according to the guidelines to determine any associated cost benefits. Method: Data collection from our prior audit was used to retrospectively identify thirteen patients considered high-risk for choledocholithiasis. Their ongoing management was mapped against the guidelines. Individual costs for the key investigations were obtained from our hospital financial data. Total cost for the different management pathways identified in clinical practice were calculated and compared against predicted costs associated with recommendations in the guidelines. We excluded the cost of laparoscopic cholecystectomy and considered a set figure for per day hospital admission related expenses. Results: Based on our previous audit data, we identified a77% positive predictive value for the ASGE risk stratification tool to determine patients at high-risk of choledocholithiasis. 47% (6/13) had an magnetic resonance cholangiopancreatography (MRCP) prior to endoscopic retrograde cholangiopancreatography (ERCP), whilst 53% (7/13) went straight for ERCP. The average length of stay in the hospital was 7 days, with an additional day and cost of £328.00 (£117 for ERCP) for patients awaiting an MRCP prior to ERCP. Per day hospital admission was valued at £838.69. When calculating total cost, we assumed all patients had admission bloods and ultrasound done as the gold standard. In doing an MRCP prior to ERCP, there was a 130% increase in cost incurred (£580.04 vs £252.04) per patient. When also considering hospital admission and the average length of stay, it was an additional £1166.69 per patient. We then calculated the exact costs incurred by the department, over a three-month period, for all patients, for key investigations or procedures done in the management of choledocholithiasis. This was compared to an estimate cost derived from the recommended pathways in the ASGE guidelines. Overall, 81% (£2048.45) saving was associated with following the guidelines compared to clinical practice. Conclusion: MRCP is the most expensive test associated with the diagnosis and management of choledocholithiasis. The ASGE guidelines recommend endoscopy without an MRCP in patients stratified as high-risk for choledocholithiasis. Our audit that focused on assessing the utility of the ASGE risk scoring system showed it to be relatively reliable for identifying high-risk patients. Our cost analysis has shown significant cost savings per patient and when considering the average length of stay associated with direct endoscopy rather than an additional MRCP. Part of this is also because of an increased average length of stay associated with waiting for an MRCP. The above data supports the ASGE guidelines for the management of high-risk for choledocholithiasis patients from a cost perspective. The only caveat is our small data set that may impact the validity of our average length of hospital stay figures and hence total cost calculations.

Keywords: cost-analysis, choledocholithiasis, risk stratification tool, general surgery

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