Search results for: bloodstream expression site

Authors: Fahrur Rozi, Daniswara Krisna Prabatha, Latief Zulfikar Chusaini

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Amidst the backdrop of Pertamina Plaju Refinery, which stands as the oldest and historically less technologically advanced among Pertamina's refineries, lies a unique challenge. Originally integrating facilities established by Shell in 1904 and Stanvac (originally Standard Oil) in 1926, the primary challenge at Plaju Refinery does not solely revolve around complexity; instead, it lies in ensuring reliability, considering its operational history of over a century. After centuries of existence, Plaju Refinery has never undergone a comprehensive major turnaround encompassing all its units. The usual practice involves partial turnarounds that are sequentially conducted across its primary, secondary, and tertiary units (utilities and offsite). However, a significant shift is on the horizon. In the Q-IV of 2023, the refinery embarks on its first-ever major turnaround since its establishment. This decision was driven by the alignment of maintenance timelines across various units. Plaju Refinery's major turnaround was scheduled for October-November 2023, spanning 45 calendar days, with the objective of enhancing the operational reliability of all refinery units. The extensive job list for this turnaround encompasses 1583 tasks across 18 units/areas, involving approximately 9000 contracted workers. In this context, the Strategy of Simultaneous Operations (SIMOPS) execution emerges as a pivotal tool to optimize time efficiency and ensure safety. A Hazard Effect Management Process (HEMP) has been employed to assess the risk ratings of each task within the turnaround. Out of the tasks assessed, 22 are deemed high-risk and necessitate mitigation. The SIMOPS approach serves as a preventive measure against potential incidents. It is noteworthy that every turnaround period at Pertamina Plaju Refinery involves SIMOPS-related tasks. In this context, enhancing the implementation strategy of "Simultaneous Operations (SIMOPS)" becomes imperative to minimize the occurrence of incidents. At least four improvements have been introduced in the enhancement process for the major turnaround at Refinery Plaju. The first improvement involves conducting systematic risk assessment and potential hazard mitigation studies for SIMOPS tasks before task execution, as opposed to the previous on-site approach. The second improvement includes the completion of SIMOPS Job Mitigation and Work Matrices Sheets, which was often neglected in the past. The third improvement emphasizes comprehensive awareness to workers/contractors regarding potential hazards and mitigation strategies for SIMOPS tasks before and during the major turnaround. The final improvement is the introduction of a daily program for inspecting and observing work in progress for SIMOPS tasks. Prior to these improvements, there was no established program for monitoring ongoing activities related to SIMOPS tasks during the turnaround. This study elucidates the steps taken to enhance SIMOPS within Pertamina, drawing from the experiences of Plaju Refinery as a guide. A real actual case study will be provided from our experience in the operational unit. In conclusion, these efforts are essential for the success of the first-ever major turnaround at Plaju Refinery, with the SIMOPS strategy serving as a central component. Based on these experiences, enhancements have been made to Pertamina's official Internal Guidelines for Executing SIMOPS Risk Mitigation, benefiting all Pertamina units.

Keywords: process safety management, turn around, oil refinery, risk assessment

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Authors: Oksana G. Cherednichenko, Anastasia L. Pilyugina, Sergey N.Lukashenko, Elena G. Gubitskaya

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The estimation of accumulated radiation doses in people professionally exposed to ionizing radiation was performed using methods of biological (chromosomal aberrations frequency in lymphocytes) and physical (radionuclides analysis in urine, whole-body radiation meter, individual thermoluminescent dosimeters) dosimetry. A group of 84 "A" category employees after their work in the territory of former Semipalatinsk test site (Kazakhstan) was investigated. The dose rate in some funnels exceeds 40 μSv/h. After radionuclides determination in urine using radiochemical and WBC methods, it was shown that the total effective dose of personnel internal exposure did not exceed 0.2 mSv/year, while an acceptable dose limit for staff is 20 mSv/year. The range of external radiation doses measured with individual thermo-luminescent dosimeters was 0.3-1.406 µSv. The cytogenetic examination showed that chromosomal aberrations frequency in staff was 4.27±0.22%, which is significantly higher than at the people from non-polluting settlement Tausugur (0.87±0.1%) (р ≤ 0.01) and citizens of Almaty (1.6±0.12%) (р≤ 0.01). Chromosomal type aberrations accounted for 2.32±0.16%, 0.27±0.06% of which were dicentrics and centric rings. The cytogenetic analysis of different types group radiosensitivity among «professionals» (age, sex, ethnic group, epidemiological data) revealed no significant differences between the compared values. Using various techniques by frequency of dicentrics and centric rings, the average cumulative radiation dose for group was calculated, and that was 0.084-0.143 Gy. To perform comparative individual dosimetry using physical and biological methods of dose assessment, calibration curves (including own ones) and regression equations based on general frequency of chromosomal aberrations obtained after irradiation of blood samples by gamma-radiation with the dose rate of 0,1 Gy/min were used. Herewith, on the assumption of individual variation of chromosomal aberrations frequency (1–10%), the accumulated dose of radiation varied 0-0.3 Gy. The main problem in the interpretation of individual dosimetry results is reduced to different reaction of the objects to irradiation - radiosensitivity, which dictates the need of quantitative definition of this individual reaction and its consideration in the calculation of the received radiation dose. The entire examined contingent was assigned to a group based on the received dose and detected cytogenetic aberrations. Radiosensitive individuals, at the lowest received dose in a year, showed the highest frequency of chromosomal aberrations (5.72%). In opposite, radioresistant individuals showed the lowest frequency of chromosomal aberrations (2.8%). The cohort correlation according to the criterion of radio-sensitivity in our research was distributed as follows: radio-sensitive (26.2%) — medium radio-sensitivity (57.1%), radioresistant (16.7%). Herewith, the dispersion for radioresistant individuals is 2.3; for the group with medium radio-sensitivity — 3.3; and for radio-sensitive group — 9. These data indicate the highest variation of characteristic (reactions to radiation effect) in the group of radio-sensitive individuals. People with medium radio-sensitivity show significant long-term correlation (0.66; n=48, β ≥ 0.999) between the values of doses defined according to the results of cytogenetic analysis and dose of external radiation obtained with the help of thermoluminescent dosimeters. Mathematical models based on the type of violation of the radiation dose according to the professionals radiosensitivity level were offered.

Keywords: biodosimetry, chromosomal aberrations, ionizing radiation, radiosensitivity

Procedia PDF Downloads 185

Authors: Ayla Hoeta

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In a post-colonial Aotearoa New Zealand, solutions by rangatahi (youth) for rangatahi are essential as is civic participation and building economic agency in an increasingly tough economic climate. Upsouth was an online community crowdsourcing platform developed by The Southern Initiative, in collaboration with Itsnoon that provides rangatahi and whānau (family) a safe space to share lived experience, thoughts and ideas about local kaupapa (issues/topics) of importance to them. The target participants were Māori indigenous peoples and Pacifica groups, aged 14 - 21 years. In the Aotearoa New Zealand context, this participant group is not likely to engage in traditional consultation processes despite being an essential constituent in helping shape better local communities, whānau and futures. The Upsouth platform was active for two years from 2018-2019 where it completed 42 callups with 4300+ participants. The web platform collates the ideas, voices, feedback, and content of users around a callup that has been commissioned by a sponsor, such as Auckland Council, Z Energy or Auckland Transport. A callup may be about a pressing challenge in a community such as climate change, a new housing development, homelessness etc. Each callup was funded by the sponsor with Upsouths main point of difference being that participants are given koha (money donation) through digital wallets for their ideas. Depending on the quality of what participants upload, the koha varies between small micropayments and larger payments. This encouraged participants to develop creative and critical thinking - upskilling for future focussed jobs, enterprise and democratic skills while earning pocket money at the same time. Upsouth enables youth-led action and voice, and empowers them to be a part of a reciprocal and creative economy. Rangatahi are encouraged to express themselves culturally, creatively, freely and in a way they are free to choose - for example, spoken word, song, dance, video, drawings, and/or poems. This challenges and changes what is considered acceptable as community engagement feedback by the local government. Many traditional engagement platforms are not as consultative, do not accept diverse types of feedback, nor incentivise this valuable expression of feedback. Upsouth is also empowering for rangatahi, since it allows them the opportunity to express their opinions directly to the government. Upsouth gained national and international recognition for the way it engages with youth: winning the Supreme Award and the Accessibility and Transparency Award at Auckland Council’s 2018 Engagement Awards, becoming a finalist in the 2018 Digital Equity and Accessibility category of International Data Corporation’s Smart City Asia and Pacific Awards. This paper will fully contextualize the challenges of rangatahi and whānau civic engagement in Aotearoa New Zealand and then present a reflective case study of the Upsouth project, with examples from some of the callups. This is intended to form part of the Divided Cities 22 conference New Ground sub-theme as a critical reflection on a design intervention, which was conceived and implemented by the lead author to overcome the post-colonial divisions of Māori, Pacifica and minority ethnic rangatahi in Aotearoa New Zealand.

Keywords: rangatahi, youth empowerment, civic engagement, enabling, relating, digital platform, participation

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Authors: Aussara Panya, Nunghathai Sawasdee, Mutita Junking, Chatchawan Srisawat, Kiattawee Choowongkomon, Pa-Thai Yenchitsomanus

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Dengue virus (DENV) infection is a global public health problem with approximately 100 million infected cases a year. Presently, there is no approved vaccine or effective drug available; therefore, the development of anti-DENV drug is urgently needed. The clinical reports revealing the positive association between the disease severity and viral titer has been reported previously suggesting that the anti-DENV drug therapy can possibly ameliorate the disease severity. Although several anti-DENV agents showed inhibitory activities against DENV infection, to date none of them accomplishes clinical use in the patients. The surface envelope (E) protein of DENV is critical for the viral entry step, which includes attachment and membrane fusion; thus, the blocking of envelope protein is an attractive strategy for anti-DENV drug development. To search the safe anti-DENV agent, this study aimed to search for novel peptide inhibitors to counter DENV infection through the targeting of E protein using a structure-based in silico design. Two selected strategies has been used including to identify the peptide inhibitor which interfere the membrane fusion process whereby the hydrophobic pocket on the E protein was the target, the destabilization of virion structure organization through the disruption of the interaction between the envelope and membrane proteins, respectively. The molecular docking technique has been used in the first strategy to search for the peptide inhibitors that specifically bind to the hydrophobic pocket. The second strategy, the peptide inhibitor has been designed to mimic the ectodomain portion of membrane protein to disrupt the protein-protein interaction. The designed peptides were tested for the effects on cell viability to measure the toxic to peptide to the cells and their inhibitory assay to inhibit the DENV infection in Vero cells. Furthermore, their antiviral effects on viral replication, intracellular protein level and viral production have been observed by using the qPCR, cell-based flavivirus immunodetection and immunofluorescence assay. None of tested peptides showed the significant effect on cell viability. The small peptide inhibitors achieved from molecular docking, Glu-Phe (EF), effectively inhibited DENV infection in cell culture system. Its most potential effect was observed for DENV2 with a half maximal inhibition concentration (IC50) of 96 μM, but it partially inhibited other serotypes. Treatment of EF at 200 µM on infected cells also significantly reduced the viral genome and protein to 83.47% and 84.15%, respectively, corresponding to the reduction of infected cell numbers. An additional approach was carried out by using peptide mimicking membrane (M) protein, namely MLH40. Treatment of MLH40 caused the reduction of foci formation in four individual DENV serotype (DENV1-4) with IC50 of 24-31 μM. Further characterization suggested that the MLH40 specifically blocked viral attachment to host membrane, and treatment with 100 μM could diminish 80% of viral attachment. In summary, targeting the hydrophobic pocket and M-binding site on the E protein by using the peptide inhibitors could inhibit DENV infection. The results provide proof of-concept for the development of antiviral therapeutic peptide inhibitors to counter DENV infection through the use of a structure-based design targeting conserved viral protein.

Keywords: dengue virus, dengue virus infection, drug design, peptide inhibitor

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Authors: Sundaram Arulmozhiraja, Kanade Shimizu, Yuta Yamamoto, Satoshi Ichikawa, Maenaka Katsumi, Hiroaki Tokiwa

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Drug discovery is shifting from small molecule based drugs targeting local active site to middle molecules (MM) targeting large, flat, and groove-shaped binding sites, for example, protein-protein interface because at least half of all targets assumed to be involved in human disease have been classified as “difficult to drug” with traditional small molecules. Hence, MMs such as peptides, natural products, glycans, nucleic acids with various high potent bioactivities become important targets for drug discovery programs in the recent years as they could be used for ‘undruggable” intracellular targets. Cell membrane permeability is one of the key properties of pharmacodynamically active MM drug compounds and so evaluating this property for the potential MMs is crucial. Computational prediction for cell membrane permeability of molecules is very challenging; however, recent advancement in the molecular dynamics simulations help to solve this issue partially. It is expected that MMs with high membrane permeability will enable drug discovery research to expand its borders towards intracellular targets. Further to understand the chemistry behind the permeability of MMs, it is necessary to investigate their conformational changes during the permeation through membrane and for that their interactions with the membrane field should be studied reliably because these interactions involve various non-bonding interactions such as hydrogen bonding, -stacking, charge-transfer, polarization dispersion, and non-classical weak hydrogen bonding. Therefore, parameters-based classical mechanics calculations are hardly sufficient to investigate these interactions rather, quantum mechanical (QM) calculations are essential. Fragment molecular orbital (FMO) method could be used for such purpose as it performs ab initio QM calculations by dividing the system into fragments. The present work is aimed to study the cell permeability of middle molecules using molecular dynamics simulations and FMO-QM calculations. For this purpose, a natural compound syringolin and its analogues were considered in this study. Molecular simulations were performed using NAMD and Gromacs programs with CHARMM force field. FMO calculations were performed using the PAICS program at the correlated Resolution-of-Identity second-order Moller Plesset (RI-MP2) level with the cc-pVDZ basis set. The simulations clearly show that while syringolin could not permeate the membrane, its selected analogues go through the medium in nano second scale. These correlates well with the existing experimental evidences that these syringolin analogues are membrane-permeable compounds. Further analyses indicate that intramolecular -stacking interactions in the syringolin analogues influenced their permeability positively. These intramolecular interactions reduce the polarity of these analogues so that they could permeate the lipophilic cell membrane. Conclusively, the cell membrane permeability of various middle molecules with potent bioactivities is efficiently studied using molecular dynamics simulations. Insight of this behavior is thoroughly investigated using FMO-QM calculations. Results obtained in the present study indicate that non-bonding intramolecular interactions such as hydrogen-bonding and -stacking along with the conformational flexibility of MMs are essential for amicable membrane permeation. These results are interesting and are nice example for this theoretical calculation approach that could be used to study the permeability of other middle molecules. This work was supported by Japan Agency for Medical Research and Development (AMED) under Grant Number 18ae0101047.

Keywords: fragment molecular orbital theory, membrane permeability, middle molecules, molecular dynamics simulation

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Authors: Mario Tauzene Afonso Matangue, Ivan Andres Sanchez Ortiz

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The Metropolitan area of Maputo (Mozambique Capital City) is located in semi-arid zone (800 mm annual rainfall) with 1101170 million inhabitants. On the west side, there are the flatlands of Infulene where the Mulauze River flows towards to the Indian Ocean, receiving at this site, the storm water contaminated with sanitary sewage from Maputo, transported through a concrete open channel. In Infulene, local communities grow salads crops such as tomato, onion, garlic, lettuce, and cabbage, which are then commercialized and consumed in several markets in Maputo City. Lettuce is the most daily consumed salad crop in different meals, generally in fast-foods, breakfasts, lunches, and dinners. However, the risk of infection by several pathogens due to the consumption of lettuce, using the Quantitative Microbial Risk Assessment (QMRA) tools, is still unknown since there are few studies or publications concerning to this matter in Mozambique. This work is aimed at determining the annual risk arising from the consumption of lettuce grown in Infulene valley, in Maputo, using QMRA tools. The exposure model was constructed upon the volume of contaminated water remaining in the lettuce leaves, the empirical relations between the number of pathogens and the indicator of microorganisms (E. coli), the consumption of lettuce (g) and reduction of pathogens (days). The reference pathogens were Vibrio cholerae, Cryptosporidium, norovirus, and Ascaris. The water quality samples (E. coli) were collected in the storm water channel from January 2016 to December 2018, comprising 65 samples, and the urban lettuce consumption data were collected through inquiry in Maputo Metropolis covering 350 persons. A non-parametric bootstrap was performed involving 10,000 iterations over the collected dataset, namely, water quality (E. coli) and lettuce consumption. The dose-response models were: Exponential for Cryptosporidium, Kummer Confluent hypergeomtric function (1F1) for Vibrio and Ascaris Gaussian hypergeometric function (2F1-(a,b;c;z) for norovirus. The annual infection risk estimates were performed using R 3.6.0 (CoreTeam) software by Monte Carlo (Latin hypercubes), a sampling technique involving 10,000 iterations. The annual infection risks values expressed by Median and the 95th percentile, per person per year (pppy) arising from the consumption of lettuce are as follows: Vibrio cholerae (1.00, 1.00), Cryptosporidium (3.91x10⁻³, 9.72x 10⁻³), nororvirus (5.22x10⁻¹, 9.99x10⁻¹) and Ascaris (2.59x10⁻¹, 9.65x10⁻¹). Thus, the consumption of the lettuce would result in greater risks than the tolerable levels ( < 10⁻³ pppy or 10⁻⁶ DALY) for all pathogens, and the Vibrio cholerae is the most virulent pathogens, according to the hit-single models followed by the Ascaris lumbricoides and norovirus. The sensitivity analysis carried out in this work pointed out that in the whole QMRA, the most important input variable was the reduction of pathogens (Spearman rank value was 0.69) between harvest and consumption followed by water quality (Spearman rank value was 0.69). The decision-makers (Mozambique Government) must strengthen the prevention measures related to pathogens reduction in lettuce (i.e., washing) and engage in wastewater treatment engineering.

Keywords: annual infections risk, lettuce, non-parametric bootstrapping, quantitative microbial risk assessment tools

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Authors: Carles Martinez-Almoyna Gual, Jiwon Choi

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Urban communities face risks of disintegration and segregation as a consequence of globalised migration processes towards urban environments. Linking social and cultural components with environmental and economic dimensions becomes the goal of all the disciplines that aim to shape more sustainable urban environments. Solutions require interdisciplinary approaches and the use of a complex array of tools. One of these tools is the implementation of urban farming, which provides a wide range of advantages for creating more inclusive spaces and integrated communities. Since food is strongly related to the values and identities of any cultural group, it can be used as a medium to promote social inclusion in the context of urban multicultural societies. By bringing people together into specific urban sites, food production can be integrated into multifunctional spaces while addressing social, economic and ecological goals. The goal of this research is to assess different approaches to urban agriculture by analysing three existing community gardens located in Newtown, a suburb of Wellington, New Zealand. As a context for developing research, Newtown offers different approaches to urban farming and is really valuable for observing current trends of socialization in diverse and multicultural societies. All three spaces are located on public land owned by Wellington City Council and confined to a small, complex and progressively denser urban area. The developed analysis was focused on social, cultural and physical dimensions, combining community engagement with different techniques of spatial assessment. At the same time, a detailed investigation of each community garden was conducted with comparative analysis methodologies. This multidirectional setting of the analysis was established for extracting from the case studies both specific and typological knowledge. Each site was analysed and categorised under three broad themes: people, space and food. The analysis revealed that all three case studies had really different spatial settings, different approaches to food production and varying profiles of supportive communities. The main differences identified were demographics, values, objectives, internal organization, appropriation, and perception of the space. The community gardens were approached as case studies for developing design research. Following participatory design processes with the different communities, the knowledge gained from the analysis was used for proposing changes in the physical environment. The end goal of the design research was to improve the capacity of the spaces to facilitate social inclusiveness. In order to generate tangible changes, a range of small, strategic and feasible spatial interventions was explored. The smallness of the proposed interventions facilitates implementation by reducing time frames, technical resources, funding needs, and legal processes, working within the community´s own realm. These small interventions are expected to be implemented over time as part of an ongoing collaboration between the different communities, the university, and the local council. The applied research methodology showcases the capacity of universities to develop civic engagement by working with real communities that have concrete needs and face overall threats of disintegration and segregation.

Keywords: community gardening, landscape architecture, participatory design, placemaking, social inclusion

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Authors: Peregrine James Dalziel, Philip Vu Tran

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Objective / Introduction: Demand for radiology services from Emergency Departments (ED) continues to increase with greater demands placed on radiology staff providing reports for the management of complex cases. Queuing theory indicates that wide variability of process time with the random nature of request arrival increases the probability of significant queues. This can lead to delays in the time-to-availability of radiology reports (TTA-RR) and potentially impaired ED patient flow. In addition, greater “cognitive workload” of greater volume may lead to reduced productivity and increased errors. We sought to quantify the potential ED flow improvements obtainable from increased radiology providers serving 3 public hospitals in Melbourne Australia. We sought to assess the potential productivity gains, quality improvement and the cost-effectiveness of increased labor inputs. Methods & Materials: The Western Health Medical Imaging Department moved from single resident coverage on weekend days 8:30 am-10:30 pm to a limited period of 2 resident coverage 1 pm-6 pm on both weekend days. The TTA-RR for weekend CT scans was calculated from the PACs database for the 8 month period symmetrically around the date of staffing change. A multivariate linear regression model was developed to isolate the improvement in TTA-RR, between the two 4-months periods. Daily and hourly scan volume at the time of each CT scan was calculated to assess the impact of varying department workload. To assess any improvement in report quality/errors a random sample of 200 studies was assessed to compare the average number of clinically significant over-read addendums to reports between the 2 periods. Cost-effectiveness was assessed by comparing the marginal cost of additional staffing against a conservative estimate of the economic benefit of improved ED patient throughput using the Australian national insurance rebate for private ED attendance as a revenue proxy. Results: The primary resident on call and the type of scan accounted for most of the explained variability in time to report availability (R2=0.29). Increasing daily volume and hourly volume was associated with increased TTA-RR (1.5m (p<0.01) and 4.8m (p<0.01) respectively per additional scan ordered within each time frame. Reports were available 25.9 minutes sooner on average in the 4 months post-implementation of double coverage (p<0.01) with additional 23.6 minutes improvement when 2 residents were on-site concomitantly (p<0.01). The aggregate average improvement in TTA-RR was 24.8 hours per weekend day This represents the increased decision-making time available to ED physicians and potential improvement in ED bed utilisation. 5% of reports from the intervention period contained clinically significant addendums vs 7% in the single resident period but this was not statistically significant (p=0.7). The marginal cost was less than the anticipated economic benefit based assuming a 50% capture of improved TTA-RR inpatient disposition and using the lowest available national insurance rebate as a proxy for economic benefit. Conclusion: TTA-RR improved significantly during the period of increased staff availability, both during the specific period of increased staffing and throughout the day. Increased labor utilisation is cost-effective compared with the potential improved productivity for ED cases requiring CT imaging.

Keywords: workflow, quality, administration, CT, staffing

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Authors: Marina Passero, Tianhua Zhai, Zuyi (Jacky) Huang

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Alzheimer’s disease has become a major public health issue, as indicated by the increasing populations of Americans living with Alzheimer’s disease. After decades of extensive research in Alzheimer’s disease, only seven drugs have been approved by Food and Drug Administration (FDA) to treat Alzheimer’s disease. Five of these drugs were designed to treat the dementia symptoms, and only two drugs (i.e., Aducanumab and Lecanemab) target the progression of Alzheimer’s disease, especially the accumulation of amyloid-b plaques. However, controversial comments were raised for the accelerated approvals of either Aducanumab or Lecanemab, especially with concerns on safety and side effects of these two drugs. There is still an urgent need for further drug discovery to target the biological processes involved in the progression of Alzheimer’s disease. Excessive cholesterol has been found to accumulate in the brain of those with Alzheimer’s disease. Cholesterol can be synthesized in both the blood and the brain, but the majority of biosynthesis in the adult brain takes place in astrocytes and is then transported to the neurons via ApoE. The blood brain barrier separates cholesterol metabolism in the brain from the rest of the body. Various proteins contribute to the metabolism of cholesterol in the brain, which offer potential targets for Alzheimer’s treatment. In the astrocytes, SREBP cleavage-activating protein (SCAP) binds to Sterol Regulatory Element-binding Protein 2 (SREBP2) in order to transport the complex from the endoplasmic reticulum to the Golgi apparatus. Cholesterol is secreted out of the astrocytes by ATP-Binding Cassette A1 (ABCA1) transporter. Lipoprotein receptors such as triggering receptor expressed on myeloid cells 2 (TREM2) internalize cholesterol into the microglia, while lipoprotein receptors such as Low-density lipoprotein receptor-related protein 1 (LRP1) internalize cholesterol into the neuron. Cytochrome P450 Family 46 Subfamily A Member 1 (CYP46A1) converts excess cholesterol to 24S-hydroxycholesterol (24S-OHC). Cholesterol has been approved for its direct effect on the production of amyloid-beta and tau proteins. The addition of cholesterol to the brain promotes the activity of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), secretase, and amyloid precursor protein (APP), which all aid in amyloid-beta production. The reduction of cholesterol esters in the brain have been found to reduce phosphorylated tau levels in mice. In this work, a computational pipeline was developed to identify the protein targets involved in cholesterol regulation in brain and further to identify chemical compounds as the inhibitors of a selected protein target. Since extensive evidence shows the strong correlation between brain cholesterol regulation and Alzheimer’s disease, a detailed literature review on genes or pathways related to the brain cholesterol synthesis and regulation was first conducted in this work. An interaction network was then built for those genes so that the top gene targets were identified. The involvement of these genes in Alzheimer’s disease progression was discussed, which was followed by the investigation of existing clinical trials for those targets. A ligand-protein docking program was finally developed to screen 1.5 million chemical compounds for the selected protein target. A machine learning program was developed to evaluate and predict the binding interaction between chemical compounds and the protein target. The results from this work pave the way for further drug discovery to regulate brain cholesterol to combat Alzheimer’s disease.

Keywords: Alzheimer’s disease, drug discovery, ligand-protein docking, gene-network analysis, cholesterol regulation

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Authors: Nicki Mohammadi, Emma Reford, Natalia Romano Spica, Laura Tabacof, Jenna Tosto-Mancuso, David Putrino, Christopher P. Kellner

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Introductory Statement: The onset of the COVID-19 pandemic demanded an unprecedented need for the rapid development, dispersal, and application of infection testing. However, despite the impressive mobilization of resources, individuals were incredibly limited in their access to tests, particularly during the initial months of the pandemic (March-April 2020) in New York City (NYC). Access to COVID-19 testing is crucial in understanding patients’ illness experiences and integral to the development of COVID-19 standard-of-care protocols, especially in the context of overall access to healthcare resources. Succinct Description of basic methodologies: 18 Patients in a COVID-19 Remote Patient Monitoring Program (Precision Recovery within the Mount Sinai Health System) were interviewed regarding their experience with COVID-19 during the first wave (March-May 2020) of the COVID-19 pandemic in New York City. Patients were asked about their experiences navigating COVID-19 diagnoses, the health care system, and their recovery process. Transcribed interviews were analyzed for thematic codes, using grounded theory to guide the identification of emergent themes and codebook development through an iterative process. Data coding was performed using NVivo12. References for the domain “testing” were then extracted and analyzed for themes and statistical patterns. Clear Indication of Major Findings of the study: 100% of participants (18/18) referenced COVID-19 testing in their interviews, with a total of 79 references across the 18 transcripts (average: 4.4 references/interview; 2.7% interview coverage). 89% of participants (16/18) discussed the difficulty of access to testing, including denial of testing without high severity of symptoms, geographical distance to the testing site, and lack of testing resources at healthcare centers. Participants shared varying perspectives on how the lack of certainty regarding their COVID-19 status affected their course of recovery. One participant shared that because she never tested positive she was shielded from her anxiety and fear, given the death toll in NYC. Another group of participants shared that not having a concrete status to share with family, friends and professionals affected how seriously onlookers took their symptoms. Furthermore, the absence of a positive test barred some individuals from access to treatment programs and employment support. Concluding Statement: Lack of access to COVID-19 testing in the first wave of the pandemic in NYC was a prominent element of patients’ illness experience, particularly during their recovery phase. While for some the lack of concrete results was protective, most emphasized the invalidating effect this had on the perception of illness for both self and others. COVID-19 testing is now widely accessible; however, those who are unable to demonstrate a positive test result but who are still presumed to have had COVID-19 in the first wave must continue to adapt to and live with the effects of this gap in knowledge and care on their recovery. Future efforts are required to ensure that patients do not face barriers to care due to the lack of testing and are reassured regarding their access to healthcare. Affiliations- 1Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, NY 2Abilities Research Center, Department of Rehabilitation and Human Performance, Icahn School of Medicine at Mount Sinai, New York, NY

Keywords: accessibility, COVID-19, recovery, testing

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Authors: Aisha Musaazi Sebunya Nakitto, Anika E. Wagner, Yusuf B. Byaruhanga, John H. Muyonga

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The prevalence and burden of diabetes are rapidly increasing globally, stemming from changes in lifestyle and dietary habits. Although several drugs are available to treat type 2 diabetes mellitus (T2DM), many are accompanied by several side effects and are often costly. Solanum anguivi Lam. fruits (SALF) are bitter berries that commonly grow in the wild and are traditionally cultivated by many globally as a remedy for T2DM. This effect is likely attributable to the presence of bioactive compounds such as phenolics, flavonoids, saponins, alkaloids, and vitamin C in SALF. In this study, we investigated the morphological characteristics of different SALF accessions and the effect of ripeness stages and thermal treatments on the bioactive compounds contents (BCC) and antioxidant activity (AA) of SALF accessions. Using the fruit fly Drosophila melanogaster (D. melanogaster) model, we explored the potential impact of dietary SALF in preventing and treating T2DM phenotypes. Morphological characterization was conducted based on descriptors of Solanum species. The BCC and AA of SALF at different ripeness stages (unripe, yellow, orange, and red) and after thermal treatments were determined using spectrophotometry, HPLC, and gravimetry. Male and female fruit flies were fed a high-sugar diet (HSD) to induce a T2DM-like phenotype, while control flies were fed on SY10 medium for up to 24 days. Experimental flies were exposed to HSD supplemented with 5 or 10 mg/ml SALF. The therapeutic and prevention effect of SALF in T2DM-like phenotype was investigated on weight, climbing activity, glucose and triglyceride contents, survival, and gene expression of PPARγ co-activator 1α fly homolog Srl and Drosophila insulin-like peptides. Methods in fly studies included Gustatory assay, Climbing assay, Glucose GOD-PAP assay, Triglyceride GPO-PAP assay, Roti-Quant®, and Real Time-PCR analysis. The ripeness stage significantly influenced SALF BCC and AA, and this was dependent on the accession. The unripe stage had the highest AA and total phenolics and flavonoids; the orange stage was rich in saponins, while the red stage had the highest alkaloid contents. Boiling and steaming increased the total phenolics and AA up to 4-fold and 3-fold, respectively. Drying at low temperatures resulted in higher phenolics and AA than the control. In the therapeutic model, the HSD-fed female flies exhibited elevated glucose levels, which exhibited a dose-dependent reduction upon exposure to a SALF-supplemented diet. Female flies fed on a SALF+ HSD exhibited a significant increase in survival compared to HSD-fed and control diet-fed flies. SALF supplementation did not alter the weights, fitness, and triglyceride levels of female flies in comparison with HSD-only-fed flies. The mRNA levels of Srl decreased in HSD-fed flies compared to the control-fed, with no effect observed in females exposed to HSD+SALF. Similarly, in the preventative model, the SALF diet resulted in higher survival of supplemented flies compared to controls. Consumption of boiled unripe SALF may result in the highest health benefits due to the high phenolic contents and antioxidant activity observed. Dietary intake of SALF significantly lowered glucose levels and increased survival of the D. melanogaster model. Additional studies in higher organisms are needed to explore the preventative and therapeutic potential of SALF in T2DM.

Keywords: antioxidant activity, bioactive compounds, bitter berries, Drosophila melanogaster, Solanum anguivi, type 2 diabetes mellitus, survival

Procedia PDF Downloads 32

Authors: E. O. Aluta, C. A. Booth, D. G. Proverbs, T. Appleby

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Challenges in the effective management of potable water have attracted global attention in recent years and remain many world regions’ major priorities. Scarcity and unavailability of potable water may potentially escalate poverty, obviate democratic expression of views and militate against inter-sectoral development. These challenges contra-indicate the inherent potentials of the resource. Thus, while creation of poverty may be regarded as a broad-based problem, it is capable of reflecting life-span reduction diseases, the friction of interests manifesting in threats and warfare, the relegation of democratic principles for authoritarian definitions and Human Rights abuse. The challenges may be identified as manifestations of ineffective management of potable water resource and therefore, regarded as major problems in environmental protection. In reaction, some nations have re-examined their laws and policies, while others have developed innovative projects, which seek to ameliorate difficulties of providing sustainable potable water. The problems resonate in Nigeria, where the legal framework supporting the supply and management of potable water has been criticized as ineffective. This has impacted more on rural community members, often regarded as ‘voiceless’. At that level, the participation of non-state actors has been identified as an effective strategy, which can improve water supply. However, there are indications that there is no pragmatic application of this, resulting in over-centralization and top-down management. Thus, this study focuses on how the participatory process may enable the development of participatory water governance framework, for use in Nigeria rural communities. The Rural Advisory Board (RAB) is proposed as a governing body to promote proximal relationships, institute democratisation borne out of participation, while enabling effective accountability and information. The RAB establishes mechanisms for effectiveness, taking into consideration Transparency, Accountability and Participation (TAP), advocated as guiding principles of decision-makers. Other tools, which may be explored in achieving these are, Laws and Policies supporting the water sector, under the direction of the Ministries and Law Courts, which ensure non-violation of laws. Community norms and values, consisting of Nigerian traditional belief system, perceptions, attitude and reality (often undermined in favour of legislations), are relied on to pave the way for enforcement. While the Task Forces consist of community members with specific designation of duties, which ensure compliance and enforceability, a cross-section of community members are assigned duties. Thus, the principle of participation is pragmatically reflected. A review of the literature provided information on the potentials of the participatory process, in potable water governance. Qualitative methodology was explored by using the semi-structured interview as strategy for inquiry. The purposive sampling strategy, consisting of homogeneous, heterogeneous and criterion techniques was applied to enable sampling. The samples, sourced from diverse positions of life, were from the study area of Delta State of Nigeria, involving three local governments of Oshimili South, Uvwie and Warri South. From the findings, there are indications that the application of the participatory process is inhered with empowerment of the rural community members to make legitimate demands for TAP. This includes the obviation of mono-decision making for the supply and management of potable water. This is capable of restructuring the top-down management to a top-down/bottom-up system.

Keywords: participation, participatory process, participatory water governance, rural advisory board

Procedia PDF Downloads 387

Authors: Mohammadjavad Sotoudeheian, Navid Farahmandian

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Cardiac hypertrophy arises in response to persistent increases in hemodynamic loads. In comparison, diabetic cardiomyopathy is defined by an abnormal myocardial changes without other cardiac-related risk factors. Pathological cardiac hypertrophy and myocardial remodeling are hallmarks of cardiovascular diseases and are risk factors for heart failure. The transcription factor forkhead box class O (FOXOs) can protect heart tissue by hostile oxidative stress and stimulating apoptosis and autophagy. FOXO proteins, as sensitive elements and mediators in response to environmental changes, have been revealed to prevent and inverse cardiac hypertrophy. FOXOs are inhibited by insulin and are critical mediators of insulin action. Insulin deficiency and uncontrolled diabetes lead to a catabolic state. FOXO1 acts downstream of the insulin-dependent pathways, which are dysregulated in diabetes. It regulates cardiomyocyte hypertrophy downstream of IGF1R/PI3K/Akt activation, which are critical regulators of cardiac hypertrophy. The complex network of signaling pathways comprising insulin/IGF-1 signaling, AMPK, JNK, and Sirtuins regulate the development of cardiovascular dysfunction by modulating the activity of FOXOs. Insulin receptors and IGF1R act via the PI3k/Akt and the MAPK/ERK pathways. Activation of Akt in response to insulin or IGF-1 induces phosphorylation of FOXOs. Increased protein synthesis induced by activation of the IGF-I/Akt/mTOR signaling pathway leads to hypertrophy. This pathway and the myostatin/Smad pathway are potent negative muscle development regulators. In cardiac muscle, insulin receptor substrates (IRS)-1 or IRS-2 activates the Akt signaling pathway and inactivate FOXO1. Under metabolic stress, p38 MAPK promotes degradation of IRS-1 and IRS-2 in cardiac myocytes and activates FOXO1, leading to cardiomyopathy. Sirt1 and FOXO1 interaction play an essential role in starvation-induced autophagy in cardiac metabolism. Inhibition of Angiotensin-II induced cardiomyocyte hypertrophy is associated with reduced FOXO1 acetylation and activation of Sirt1. The NF-κB, ERK, and FOXOs are de-acetylated by SIRT1. De-acetylation of FOXO1 induces the expression of genes involved in autophagy and stimulates autophagy flux. Therefore, under metabolic stress, FOXO1 can cause diabetic cardiomyopathy. The overexpression of FOXO1 leads to decreased cardiomyocyte size and suppresses cardiac hypertrophy through inhibition of the calcineurin–NFAT pathway. Diabetes mellitus is associated with elevation of O-GlcNAcylation. Some of its binding partners regulate the substrate selectivity of O-GlcNAc transferase (OGT). O-GlcNAcylation of essential contractile proteins may inhibit protein-protein interactions, reduce calcium sensitivity, and modulate contractile function. Uridine diphosphate (UDP)-GlcNAc is the obligatory substrate of OGT, which catalyzes a reversible post-translational protein modification. The increase of O-GlcNAcylation is accompanied by impaired cardiac hypertrophy in diabetic hearts. Inhibition of O-GlcNAcylation blocks activation of ERK1/2 and hypertrophic growth. O-GlcNAc modification on NFAT is required for its translocation from the cytosol to the nucleus, where NFAT stimulates the transcription of various hypertrophic genes. Inhibition of O-GlcNAcylation dampens NFAT-induced cardiac hypertrophic growth. Transcriptional activity of FOXO1 is enriched by improved O-GlcNAcylation upon high glucose stimulation or OGT overexpression. In diabetic conditions, the modification of FOXO1 by O-GlcNAc is promoted in cardiac troponin I and myosin light chain 2. Therefore targeting O-GlcNAcylation represents a potential therapeutic option to prevent hypertrophy in the diabetic heart.

Keywords: diabetes, cardiac hypertrophy, O-GlcNAcylation, FOXO1, Akt, PI3K, AMPK, insulin

Procedia PDF Downloads 108

Authors: Ivone R. Oliveira, Isabela S. Gonçalves, Tiago M. B. Campos, Leandro J. Raniero, Luana M. R. Vasconcellos, João H. Lopes

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Originally, the principles of guided tissue/bone regeneration (GTR/GBR) were followed to restore the architecture and functionality of the periodontal system. In essence, a biocompatible polymer-based occlusive membrane is used as a barrier to prevent migration of epithelial and connective tissue to the regenerating site. In this way, progenitor cells located in the remaining periodontal ligament can recolonize the root area and differentiate into new periodontal tissues, alveolar bone, and new connective attachment. The use of synthetic or collagen-derived membranes with or without calcium phosphate-based bone graft materials has been the treatment used. Ideally, these membranes need to exhibit sufficient initial mechanical strength to allow handling and implantation, withstand the various mechanical stresses suffered during surgery while maintaining their integrity, and support the process of bone tissue regeneration and repair by resisting cellular traction forces and wound contraction forces during tissue healing in vivo. Although different RTG/ROG products are available on the market, they have serious deficiencies in terms of mechanical strength. Aiming to improve the mechanical strength and osteogenic properties of the membrane, this work evaluated the production of membranes that integrate the biocompatibility of the natural polymer (silk fibroin - FS) and the synthetic polymer poly(vinyl pyrrolidone - PVP) with graphene nanoplates (NPG) and gold nanoparticles (AuNPs), using the electrospinning equipment (AeroSpinner L1.0 from Areka) which allows the execution of high voltage spinning and/or solution blowing and with a high production rate, enabling development on an industrial scale. Silk fibroin uniquely solved many of the problems presented by collagen and was used in this work because it has unique combined merits, such as programmable biodegradability, biocompatibility and sustainable large-scale production. Graphene has attracted considerable attention in recent years as a potential biomaterial for mechanical reinforcement because of its unique physicochemical properties and was added to improve the mechanical properties of the membranes associated or not with the presence of AuNPs, which have shown great potential in regulating osteoblast activity. The preparation of FS from silkworm cocoons involved cleaning, degumming, dissolution in lithium bromide, dialysis, lyophilization and dissolution in hexafluoroisopropanol (HFIP) to prepare the solution for electrospinning, and crosslinking tests were performed in methanol. The NPGs were characterized and underwent treatment in nitric acid for functionalization to improve the adhesion of the nanoplates to the PVP fibers. PVP-NPG membranes were produced with 0.5, 1.0 and 1.5 wt% functionalized or not and evaluated by SEM/FEG, FTIR, mechanical strength and cell culture assays. Functionalized GNP particles showed stronger binding, remaining adhered to the fibers. Increasing the graphene content resulted in higher mechanical strength of the membrane and greater biocompatibility. The production of FS-PVP-NPG-AuNPs hybrid membranes was performed by electrospinning in separate syringes and simultaneously the FS solution and the solution containing PVP-NPG 1.5 wt% in the presence or absence of AuNPs. After cross-linking, they were characterized by SEM/FEG, FTIR and behavior in cell culture. The presence of NPG-AuNPs increased the viability and the presence of mineralization nodules.

Keywords: barrier membranes, silk fibroin, nanoparticles, tissue regeneration.

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Authors: Ajit Rai, Hamza Deroui, Blandine Vacher, Khwansiri Ninpan, Arthur Aumont, Francesco Vitillo, Robert Plana

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Large-scale critical industrial scheduling problems are based on Resource-Constrained Project Scheduling Problems (RCPSP), that necessitate integration with other optimization problems (e.g., vehicle routing, supply chain, or unique industrial ones), thus requiring practical solutions (i.e., modular, computationally efficient with feasible solutions). To the best of our knowledge, the current industrial state of the art is not addressing this holistic problem. We propose an original modular solution that answers the issues exhibited by the delivery of complex projects. With three interlinked entities (project, task, resources) having their constraints, it uses a greedy heuristic with a dynamic cost function for each task with a situational assessment at each time step. It handles large-scale data and can be easily integrated with other optimization problems, already existing industrial tools and unique constraints as required by the use case. The solution has been tested and validated by domain experts on three use cases: outage management in Nuclear Power Plants (NPPs), planning of future NPP maintenance operation, and application in the defense industry on supply chain and factory relocation. In the first use case, the solution, in addition to the resources’ availability and tasks’ logical relationships, also integrates several project-specific constraints for outage management, like, handling of resource incompatibility, updating of tasks priorities, pausing tasks in a specific circumstance, and adjusting dynamic unit of resources. With more than 20,000 tasks and multiple constraints, the solution provides a feasible schedule within 10-15 minutes on a standard computer device. This time-effective simulation corresponds with the nature of the problem and requirements of several scenarios (30-40 simulations) before finalizing the schedules. The second use case is a factory relocation project where production lines must be moved to a new site while ensuring the continuity of their production. This generates the challenge of merging job shop scheduling and the RCPSP with location constraints. Our solution allows the automation of the production tasks while considering the rate expectation. The simulation algorithm manages the use and movement of resources and products to respect a given relocation scenario. The last use case establishes a future maintenance operation in an NPP. The project contains complex and hard constraints, like on Finish-Start precedence relationship (i.e., successor tasks have to start immediately after predecessors while respecting all constraints), shareable coactivity for managing workspaces, and requirements of a specific state of "cyclic" resources (they can have multiple states possible with only one at a time) to perform tasks (can require unique combinations of several cyclic resources). Our solution satisfies the requirement of minimization of the state changes of cyclic resources coupled with the makespan minimization. It offers a solution of 80 cyclic resources with 50 incompatibilities between levels in less than a minute. Conclusively, we propose a fast and feasible modular approach to various industrial scheduling problems that were validated by domain experts and compatible with existing industrial tools. This approach can be further enhanced by the use of machine learning techniques on historically repeated tasks to gain further insights for delay risk mitigation measures.

Keywords: deterministic scheduling, optimization coupling, modular scheduling, RCPSP

Procedia PDF Downloads 201

Authors: Simon J. Wilde, David M. Herold, Michael J. Bryant

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Social media networks have become the hotbed for advertising activities due mainly to their increasing consumer/user base and, secondly, owing to the ability of marketers to accurately measure ad exposure and consumer-based insights on such networks. More than half of the world’s population (4.8 billion) now uses social media (60%), with 150 million new users having come online within the last 12 months (to June 2022). As the use of social media networks by users grows, key business strategies used for interacting with these potential customers have matured, especially social media advertising. Unlike other traditional media outlets, social media advertising is highly interactive and digital channel specific. Social media advertisements are clearly targetable, providing marketers with an extremely powerful marketing tool. Yet despite the measurable benefits afforded to businesses engaged in social media advertising, recent controversies (such as the relationship between Facebook and Cambridge Analytica in 2018) have only heightened the role trust and privacy play within these social media networks. Using a web-based quantitative survey instrument, survey participants were recruited via a reputable online panel survey site. Respondents to the survey represented social media users from all states and territories within Australia. Completed responses were received from a total of 258 social media users. Survey respondents represented all core age demographic groupings, including Gen Z/Millennials (18-45 years = 60.5% of respondents) and Gen X/Boomers (46-66+ years = 39.5% of respondents). An adapted ADTRUST scale, using a 20 item 7-point Likert scale, measured trust in social media advertising. The ADTRUST scale has been shown to be a valid measure of trust in advertising within traditional media, such as broadcast media and print media, and, more recently, the Internet (as a broader platform). The adapted scale was validated through exploratory factor analysis (EFA), resulting in a three-factor solution. These three factors were named reliability, usefulness and affect, and the willingness to rely on. Factor scores (weighted measures) were then calculated for these factors. Factor scores are estimates of the scores survey participants would have received on each of the factors had they been measured directly, with the following results recorded (Reliability = 4.68/7; Usefulness and Affect = 4.53/7; and Willingness to Rely On = 3.94/7). Further statistical analysis (independent samples t-test) determined the difference in factor scores between the factors when age (Gen Z/Millennials vs. Gen X/Boomers) was utilized as the independent, categorical variable. The results showed the difference in mean scores across all three factors to be statistically significant (p<0.05) for these two core age groupings: (1) Gen Z/Millennials Reliability = 4.90/7 vs. Gen X/Boomers Reliability = 4.34/7; (2) Gen Z/Millennials Usefulness and Affect = 4.85/7 vs Gen X/Boomers Usefulness and Affect = 4.05/7; and (3) Gen Z/Millennials Willingness to Rely On = 4.53/7 vs Gen X/Boomers Willingness to Rely On = 3.03/7. The results clearly indicate that older social media users lack trust in the quality of information conveyed in social media ads when compared to younger, more social media-savvy consumers. This is especially evident with respect to Factor 3 (Willingness to Rely On), whose underlying variables reflect one’s behavioral intent to act based on the information conveyed in advertising. These findings can be useful to marketers, advertisers, and brand managers in that the results highlight a critical need to design ‘authentic’ advertisements on social media sites to better connect with these older users in an attempt to foster positive behavioral responses from within this large demographic group – whose engagement with social media sites continues to increase year on year.

Keywords: social media advertising, trust, older consumers, internet studies

Procedia PDF Downloads 43

Authors: Rob Schindler

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Industry-standard methods of mitigating erosion of seabed sediments rely on ‘hard engineering’ approaches which have numerous environmental shortcomings: (1) direct loss of habitat by smothering of benthic species, (2) disruption of sediment transport processes, damaging geomorphic and ecosystem functionality (3) generation of secondary erosion problems, (4) introduction of material that may propagate non-local species, and (5) provision of pathways for the spread of invasive species. Recent studies have also revealed the importance of biological cohesion, the result of naturally occurring extra-cellular polymeric substances (EPS), in stabilizing natural sediments. Mimicking the strong bonding kinetics through the deliberate addition of EPS to sediments – henceforth termed ‘biostabilisation’ - offers a means in which to mitigate against erosion induced by structures or episodic increases in hydrodynamic forcing (e.g. storms and floods) whilst avoiding, or reducing, hard engineering. Here we present unique experiments that systematically examine how biostabilisation reduces scour around a monopile in a current, a first step to realizing the potential of this new method of scouring reduction for a wide range of engineering purposes in aquatic substrates. Experiments were performed in Plymouth University’s recirculating sediment flume which includes a recessed scour pit. The model monopile was 0.048 m in diameter, D. Assuming a prototype monopile diameter of 2.0 m yields a geometric ratio of 41.67. When applied to a 10 m prototype water depth this yields a model depth, d, of 0.24 m. The sediment pit containing the monopile was filled with different biostabilised substrata prepared using a mixture of fine sand (D50 = 230 μm) and EPS (Xanthan gum). Nine sand-EPS mixtures were examined spanning EPS contents of 0.0% < b0 < 0.50%. Scour development was measured using a laser point gauge along a 530 mm centreline at 10 mm increments at regular periods over 5 h. Maximum scour depth and excavated area were determined at different time steps and plotted against time to yield equilibrium values. After 5 hours the current was stopped and a detailed scan of the final scour morphology was taken. Results show that increasing EPS content causes a progressive reduction in the equilibrium depth and lateral extent of scour, and hence excavated material. Very small amounts equating to natural communities (< 0.1% by mass) reduce scour rate, depth and extent of scour around monopiles. Furthermore, the strong linear relationships between EPS content, equilibrium scour depth, excavation area and timescales of scouring offer a simple index on which to modify existing scour prediction methods. We conclude that the biostabilisation of sediments with EPS may offer a simple, cost-effective and ecologically sensitive means of reducing scour in a range of contexts including OWFs, bridge piers, pipeline installation, and void filling in rock armour. Biostabilisation may also reduce economic costs through (1) Use of existing site sediments, or waste dredged sediments (2) Reduced fabrication of materials, (3) Lower transport costs, (4) Less dependence on specialist vessels and precise sub-sea assembly. Further, its potential environmental credentials may allow sensitive use of the seabed in marine protection zones across the globe.

Keywords: biostabilisation, EPS, marine, scour

Procedia PDF Downloads 167

Authors: Michael Ray Brunt

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China has been the site of some of the most significant earthquakes in history; however, earthquake monitoring has long been the provenance of universities and research institutions. The China Digital Seismographic Network was initiated in 1983 and improved significantly during 1992-1993. Data from the CDSN is widely used by government and research institutions, and, generally, this data is not readily accessible to middle and high school students. An educational seismic network in China is needed to provide collaboration and research opportunities for students and engaging students around the country in scientific understanding of earthquake hazards and risks while promoting community awareness. In 2022, the Tsinghua International School (THIS) Seismology Team, made up of enthusiastic students and facilitated by two experienced teachers, was established. As a group, the team’s objective is to install seismographs in schools throughout China, thus creating an educational seismic network that shares data from the THIS Educational Seismic Network (THIS-ESN) and facilitates collaboration. The THIS-ESN initiative will enhance education and outreach in China about earthquake risks and hazards, introduce seismology to a wider audience, stimulate interest in research among students, and develop students’ programming, data collection and analysis skills. It will also encourage and inspire young minds to pursue science, technology, engineering, the arts, and math (STEAM) career fields. The THIS-ESN utilizes small, low-cost RaspberryShake seismographs as a powerful tool linked into a global network, giving schools and the public access to real-time seismic data from across China, increasing earthquake monitoring capabilities in the perspective areas and adding to the available data sets regionally and worldwide helping create a denser seismic network. The RaspberryShake seismograph is compatible with free seismic data viewing platforms such as SWARM, RaspberryShake web programs and mobile apps are designed specifically towards teaching seismology and seismic data interpretation, providing opportunities to enhance understanding. The RaspberryShake is powered by an operating system embedded in the Raspberry Pi, which makes it an easy platform to teach students basic computer communication concepts by utilizing processing tools to investigate, plot, and manipulate data. THIS Seismology Team believes strongly in creating opportunities for committed students to become part of the seismological community by engaging in analysis of real-time scientific data with tangible outcomes. Students will feel proud of the important work they are doing to understand the world around them and become advocates spreading their knowledge back into their homes and communities, helping to improve overall community resilience. We trust that, in studying the results seismograph stations yield, students will not only grasp how subjects like physics and computer science apply in real life, and by spreading information, we hope students across the country can appreciate how and why earthquakes bear on their lives, develop practical skills in STEAM, and engage in the global seismic monitoring effort. By providing such an opportunity to schools across the country, we are confident that we will be an agent of change for society.

Keywords: collaboration, outreach, education, seismology, earthquakes, public awareness, research opportunities

Procedia PDF Downloads 73

Authors: Claire Limoge Schraen, Philippe Gueguen, Cedric Giry, Cedric Desprez, Frédéric Ragueneau

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Mediterranean area is characterized by numerous monumental or vernacular masonry structures illustrating old ways of build and live. Those precious buildings are often poorly documented, present complex shapes and loadings, and are protected by the States, leading to legal constraints. This area also presents a moderate to high seismic activity. Even moderate earthquakes can be magnified by local site effects and cause collapse or significant damage. Moreover the structural resistance of masonry buildings, especially when less famous or located in rural zones has been generally lowered by many factors: poor maintenance, unsuitable restoration, ambient pollution, previous earthquakes. Recent earthquakes prove that any damage to these architectural witnesses to our past is irreversible, leading to the necessity of acting preventively. This means providing preventive assessments for hundreds of structures with no or few documents. In this context we want to propose a general method, based on hierarchized numerical models, to provide preliminary structural diagnoses at a regional scale, indicating whether more precise investigations and models are necessary for each building. To this aim, we adapt different tools, being developed such as photogrammetry or to be created such as a preprocessor starting from pictures to build meshes for a FEM software, in order to allow dynamic studies of the buildings of the panel. We made an inventory of 198 baroque chapels and churches situated in the French Alps. Then their structural characteristics have been determined thanks field surveys and the MicMac photogrammetric software. Using structural criteria, we determined eight types of churches and seven types for chapels. We studied their dynamical behavior thanks to CAST3M, using EC8 spectrum and accelerogramms of the studied zone. This allowed us quantifying the effect of the needed simplifications in the most sensitive zones and choosing the most effective ones. We also proposed threshold criteria based on the observed damages visible in the in situ surveys, old pictures and Italian code. They are relevant in linear models. To validate the structural types, we made a vibratory measures campaign using vibratory ambient noise and velocimeters. It also allowed us validating this method on old masonry and identifying the modal characteristics of 20 churches. Then we proceeded to a dynamic identification between numerical and experimental modes. So we updated the linear models thanks to material and geometrical parameters, often unknown because of the complexity of the structures and materials. The numerically optimized values have been verified thanks to the measures we made on the masonry components in situ and in laboratory. We are now working on non-linear models redistributing the strains. So we validate the damage threshold criteria which we use to compute the vulnerability curves of each defined structural type. Our actual results show a good correlation between experimental and numerical data, validating the final modeling simplifications and the global method. We now plan to use non-linear analysis in the critical zones in order to test reinforcement solutions.

Keywords: heritage structures, masonry numerical modeling, seismic vulnerability assessment, vibratory measure

Procedia PDF Downloads 493

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

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

Keywords: antibiotics, cannula, Klebsiella pneumoniae, septic emboli

Procedia PDF Downloads 163

Authors: Lauren B. Birney

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The project utilizes the Billion Oyster Project (BOP-CCERS) place-based “restoration through education” model to promote computational thinking in NYC high school teachers and their students. Key learning standards such as Next Generation Science Standards and the NYC CS4All Equity and Excellence initiative are used to develop a computer science curriculum that connects students to their Harbor through hands-on activities based on BOP field science and educational programming. Project curriculum development is grounded in BOP-CCERS restoration science activities and data collection, which are enacted by students and educators at two Restoration Science STEM Hubs or conveyed through virtual materials. New York City Public School teachers with relevant experience are recruited as consultants to provide curriculum assessment and design feedback. The completed curriculum units are then conveyed to NYC high school teachers through professional learning events held at the Pace University campus and led by BOP educators. In addition, Pace University educators execute the Summer STEM Institute, an intensive two-week computational thinking camp centered on applying data analysis tools and methods to BOP-CCERS data. Both qualitative and quantitative analyses were performed throughout the five-year study. STEM+C – Community Based Restoration STEM Hubs. STEM Hubs are active scientific restoration sites capable of hosting school and community groups of all grade levels and professional scientists and researchers conducting long-term restoration ecology research. The STEM Hubs program has grown to include 14 STEM Hubs across all five boroughs of New York City and focuses on bringing in-field monitoring experience as well as coastal classroom experience to students. Restoration Science STEM Hubs activities resulted in: the recruitment of 11 public schools, 6 community groups, 12 teachers, and over 120 students receiving exposure to BOP activities. Field science protocols were designed exclusively around the use of the Oyster Restoration Station (ORS), a small-scale in situ experimental platforms which are suspended from a dock or pier. The ORS is intended to be used and “owned” by an individual school, teacher, class, or group of students, whereas the STEM Hub is explicitly designed as a collaborative space for large-scale community-driven restoration work and in-situ experiments. The ORS is also an essential tool in gathering Harbor data from disparate locations and instilling ownership of the research process amongst students. As such, it will continue to be used in that way. New and previously participating students will continue to deploy and monitor their own ORS, uploading data to the digital platform and conducting analysis of their own harbor-wide datasets. Programming the STEM Hub will necessitate establishing working relationships between schools and local research institutions. NYHF will provide introductions and the facilitation of initial workshops in school classrooms. However, once a particular STEM Hub has been established as a space for collaboration, each partner group, school, university, or CBO will schedule its own events at the site using the digital platform’s scheduling and registration tool. Monitoring of research collaborations will be accomplished through the platform’s research publication tool and has thus far provided valuable information on the projects’ trajectory, strategic plan, and pathway.

Keywords: environmental science, citizen science, STEM, technology

Procedia PDF Downloads 98

Authors: Catherine Bradshaw

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Educators often report difficulty managing behavior problems and other mental health concerns that students display at school. These concerns also interfere with the learning process and can create distraction for teachers and other students. As such, schools play an important role in both preventing and intervening with students who experience these types of challenges. A number of models have been proposed to serve as a framework for delivering prevention and early intervention services in schools. One such model is called Positive Behavioral Interventions and Supports (PBIS), which has been scaled-up to over 26,000 schools in the U.S. and many other countries worldwide. PBIS aims to improve a range of student outcomes through early detection of and intervention related to behavioral and mental health symptoms. PBIS blends and applies social learning, behavioral, and organizational theories to prevent disruptive behavior and enhance the school’s organizational health. PBIS focuses on creating and sustaining tier 1 (universal), tier 2 (selective), and tier 3 (individual) systems of support. Most schools using PBIS have focused on the core elements of the tier 1 supports, which includes the following critical features. The formation of a PBIS team within the school to lead implementation. Identification and training of a behavioral support ‘coach’, who serves as a on-site technical assistance provider. Many of the individuals identified to serve as a PBIS coach are also trained as a school psychologist or guidance counselor; coaches typically have prior PBIS experience and are trained to conduct functional behavioral assessments. The PBIS team also identifies a set of three to five positive behavioral expectations that are implemented for all students and by all staff school-wide (e.g., ‘be respectful, responsible, and ready to learn’); these expectations are posted in all settings across the school, including in the classroom, cafeteria, playground etc. All school staff define and teach the school-wide behavioral expectations to all students and review them regularly. Finally, PBIS schools develop or adopt a school-wide system to reward or reinforce students who demonstrate those 3-5 positive behavioral expectations. Staff and administrators create an agreed upon system for responding to behavioral violations that include definitions about what constitutes a classroom-managed vs. an office-managed discipline problem. Finally, a formal system is developed to collect, analyze, and use disciplinary data (e.g., office discipline referrals) to inform decision-making. This presentation provides a brief overview of PBIS and reports findings from a series of four U.S. based longitudinal randomized controlled trials (RCTs) documenting the impacts of PBIS on school climate, discipline problems, bullying, and academic achievement. The four RCTs include 80 elementary, 40 middle, and 58 high schools and results indicate a broad range of impacts on multiple student and school-wide outcomes. The session will highlight lessons learned regarding PBIS implementation and scale-up. We also review the ways in which PBIS can help educators and school leaders engage in data-based decision-making and share data with other decision-makers and stakeholders (e.g., students, parents, community members), with the overarching goal of increasing use of evidence-based programs in schools.

Keywords: positive behavioral interventions and supports, mental health, randomized trials, school-based prevention

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Authors: Pauline Nyssen, Ange Mouithys-Mickalad, Maryse Hoebeke

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Inflammation is a complex physiological phenomenon involving chemical and enzymatic mechanisms. Polymorphonuclear neutrophil leukocytes (PMNs) play an important role by producing reactive oxygen species (ROS) and releasing myeloperoxidase (MPO), a pro-oxidant enzyme. Released both in the phagolysosome and the extracellular medium, MPO produces during its peroxidase and halogenation cycles oxidant species, including hypochlorous acid, involved in the destruction of pathogen agents, like bacteria or viruses. Inflammatory pathologies, like rheumatoid arthritis, atherosclerosis induce an excessive stimulation of the PMNs and, therefore, an uncontrolled release of ROS and MPO in the extracellular medium, causing severe damages to the surrounding tissues and biomolecules such as proteins, lipids, and DNA. The treatment of chronic inflammatory pathologies remains a challenge. For many years, MPO has been used as a target for the development of effective treatments. Numerous studies have been focused on the design of new drugs presenting more efficient MPO inhibitory properties. However, some designed inhibitors can be toxic. An alternative consists of assessing the potential inhibitory action of clinically-known molecules, having antioxidant activity. Propofol, 2,6-diisopropyl phenol, which is used as an intravenous anesthetic agent, meets these requirements. Besides its anesthetic action employed to induce a sedative state during surgery or in intensive care units, propofol and its injectable form Diprivan indeed present antioxidant properties and act as ROS and free radical scavengers. A study has also evidenced the ability of propofol to inhibit the formation of the neutrophil extracellular traps fibers, which are important to trap pathogen microorganisms during the inflammation process. The aim of this study was to investigate the potential inhibitory action mechanism of propofol and Diprivan on MPO activity. To go into the anti-inflammatory action of propofol in-depth, two of its oxidative derivatives, 2,6-diisopropyl-1,4-p-benzoquinone (PPFQ) and 3,5,3’,5’-tetra isopropyl-(4,4’)-diphenoquinone (PPFDQ), were studied regarding their inhibitory action. Specific immunological extraction followed by enzyme detection (SIEFED) and molecular modeling have evidenced the low anti-catalytic action of propofol. Stopped-flow absorption spectroscopy and direct MPO activity analysis have proved that propofol acts as a reversible MPO inhibitor by interacting as a reductive substrate in the peroxidase cycle and promoting the accumulation of redox compound II. Overall, Diprivan exhibited a weaker inhibitory action than the active molecule propofol. In contrast, PPFQ seemed to bind and obstruct the enzyme active site, preventing the trigger of the MPO oxidant cycles. PPFQ induced a better chlorination cycle inhibition at basic and neutral pH in comparison to propofol. PPFDQ did not show any MPO inhibition activity. The three interest molecules have also demonstrated their inhibition ability on an important step of the inflammation pathway, the PMNs superoxide anions production, thanks to EPR spectroscopy and chemiluminescence. In conclusion, propofol presents an interesting immunomodulatory activity by acting as a reductive substrate in the peroxidase cycle of MPO, slowing down its activity, whereas PPFQ acts more as an anti-catalytic substrate. Although PPFDQ has no impact on MPO, it can act on the inflammation process by inhibiting the superoxide anions production by PMNs.

Keywords: Diprivan, inhibitor, myeloperoxidase, propofol, spectroscopy

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Authors: Milena Nanova, Martin Georgiev, Radul Shishkov, Damyan Damov

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Modern residential architecture is increasingly influenced by rapid urbanization, technological advancements, and growing investor expectations. The integration of AI and digital tools such as CAD and BIM (Building Information Modelling) are transforming the design process by improving efficiency, accuracy, and speed. However, urban development faces challenges, including the high competition for viable sites and the time-consuming nature of traditional investment feasibility studies and architectural planning. Finding and analysing suitable sites for residential development is complicated by intense competition and rising investor demands. Investors require quick assessments of property potential to avoid missing opportunities, while traditional architectural design processes are relying on experience of the team and can be time consuming, adding pressure to make fast, effective decisions. The widespread use of CAD tools has sped up the drafting process, enhancing both accuracy and efficiency. Digital tools allow designers to manipulate drawings quickly, reducing the time spent on revisions. BIM further advances this by enabling native 3D modelling, where changes to a design in one view are automatically reflected in all others, minimizing errors and saving time. AI is becoming an integral part of architectural design software. While AI is currently being incorporated into existing programs like AutoCAD, Revit, and ArchiCAD, its full potential is reached in parametric modelling. In this process, designers define parameters (e.g., building size, layout, and materials), and the software generates multiple design variations based on those inputs. This method accelerates the design process by automating decisions and enabling quick generation of alternative solutions. The study utilizes generative design, a specific application of parametric modelling which uses AI to explore a wide range of design possibilities based on predefined criteria. It optimizes designs through iterations, testing many variations to find the best solutions. This process is particularly beneficial in the early stages of design, where multiple options are explored before refining the best ones. AI’s ability to handle complex mathematical tasks allows it to generate unconventional yet effective designs that a human designer might overlook. Residential architecture, with its anticipated and typical layouts and modular nature, is especially suitable for generative design. The relationships between rooms and the overall organization of apartment units follow logical patterns, making it an ideal candidate for parametric modelling. Using these tools, architects can quickly explore various apartment configurations, considering factors like apartment sizes, types, and circulation patterns, and identify the most efficient layout for a given site. Parametric modelling and generative design offer significant benefits to residential architecture by streamlining the design process, enabling faster decision-making, and optimizing building layouts. These technologies allow architects and developers to analyse numerous design possibilities, improving outcomes while responding to the challenges of urban development. By integrating AI-driven generative design, the architecture industry can enhance creativity, efficiency, and adaptability in residential projects.

Keywords: architectural design, residential buildings, generative design, parametric models, workflow optimization

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Authors: Siti Rahayu, Khairulniza Mohd Puat, Kesavan R., Mohammad Harris A., Jalila, Kunalan G., Fazir Mohamad

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The greatest challenge has been in establishing and maintaining the dedicated nursing team. Continuity is served when nurses are assigned exclusively for managing wound, where they can continue to build expertise and skills. In addition, there is a growing incidence of chronic wounds and recognition of the complexity involved in caring for these patients. We would like to share 4 cases with different techniques of wound management. 1st case, 39 years old gentleman with underlying rheumatoid arthritis with chronic periprosthetic joint infection of right total knee replacement presented with persistent drainage over right knee. Patient was consulted for two stage revision total knee replacement. However, patient only agreed for debridement and retention of implant. After debridement, large medial and lateral wound was treated with Instillation Negative Pressure Wound Therapy Dressings. After several cycle, the wound size reduced, and conventional dressing was applied. 2nd case, 58 years old gentleman with underlying diabetes presented with right foot necrotizing fasciitis with gangrene of 5th toe. He underwent extensive debridement of foot with rays’ amputation of 5th toe. Post debridement patient was started on Instillation Negative Pressure Wound Therapy Dressings. After several cycle of VAC, the wound bed was prepared, and he underwent split skin graft over right foot. 3 rd case, 60 years old gentleman with underlying diabetes mellitus presented with right foot necrotizing soft tissue infection. He underwent rays’ amputation and extensive wound debridement. Upon stabilization of general condition, patient was discharge with regular wound dressing by same nurse and doctor during each visit to clinic follow up. After 6 months of follow up, the wound healed well. 4th case, 38-year-old gentleman had alleged motor vehicle accident and sustained closed fracture right tibial plateau. Open reduction and proximal tibial locking plate were done. At 2 weeks post-surgery, the patient presented with warm, erythematous leg and pus discharge from the surgical site. Empirical antibiotic was started, and wound debridement was done. Intraoperatively, 50cc pus was evacuated, unhealthy muscle and tissue debrided. No loosening of the implant. Patient underwent multiple wound debridement. At 2 weeks post debridement wound healed well, but the proximal aspect was unable to close immediately. This left the proximal part of the implant to be exposed. Patient was then put on VAC dressing for 3 weeks until healthy granulation tissue closes the implant. Meanwhile, antibiotic was change according to culture and sensitivity. At 6 weeks post the first debridement, the wound was completely close, and patient was discharge home well. At 3 months post operatively, patient wound and fracture healed uneventfully and able to ambulate independently. Complex wounds are too serious to be dealt with. Team managing complex wound need continuous support through the provision of educational tools to support their professional development, engagement with local and international expert, as well as highquality products that increase efficiencies in services

Keywords: VAC (Vacuum Assisted Closure), empirical- initial antibiotics, NPWT- negative pressure wound therapy, NF- necrotizing fasciitis, gangrene- blackish discoloration due to poor blood supply

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Authors: Yogesh Dalvi, Ruby Varghese, Nibu Varghese, C. K. Krishnan Nair

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Introduction: The Genus Phellinus, locally known as Phansomba is a well-known traditional folk medicine. Especially, in Western Ghats of India, many tribes use several species of Phellinus for various ailments related to teeth, throat, tongue, stomach and even wound healing. It is one of the few mushrooms which play a pivotal role in Ayurvedic Dravyaguna. Aim: The present study focuses on to investigate phytochemical analysis, antioxidant, and antitumor (in vitro and in vivo) potential of Phellinus robinae from South India, Kerala Material and Methods: The present study explores the following: 1. Phellinus samples were collected from Ranni, Pathanamthitta district of Kerala state, India from Artocarpus heterophyllus Lam. and species were identified using rDNA region. 2. The fruiting body was shadow dried, powdered and extracted with 50% alcohol using water bath at 60°C which was further condensed by rotary evaporator and lyophilized at minus 40°C temperature. 3. Secondary metabolites were analyzed by using various phytochemical screening assay (Hager’s Test, Wagner’s Test, Sodium hydroxide Test, Lead acetate Test, Ferric chloride Test, Folin-ciocalteu Test, Foaming Test, Benedict’s test, Fehling’s Test and Lowry’s Test). 4. Antioxidant and free radical scavenging activity were analyzed by DPPH, FRAP and Iron chelating assay. 5. The antitumor potential of Water alcohol extract of Phellinus (PAWE) is evaluated through In vitro condition by Trypan blue dye exclusion method in DLA cell line and In vivo by murine model. Result and Discussion: Preliminary phytochemical screening by various biochemical tests revealed presence of a variety of active secondary molecules like alkaloids, flavanoids, saponins, carbohydrate, protein and phenol. In DPPH and FRAP assay PAWE showed significantly higher antioxidant activity as compared to standard Ascorbic acid. While, in Iron chelating assay, PAWE exhibits similar antioxidant activity that of Butylated Hydroxytoluene (BHT) as standard. Further, in the in vitro study, PAWE showed significant inhibition on DLA cell proliferation in dose dependent manner and showed no toxicity on mice splenocytes, when compared to standard chemotherapy drug doxorubicin. In vivo study, oral administration of PAWE showed dose dependent tumor regression in mice and also raised the immunogenicity by restoring levels of antioxidant enzymes in liver and kidney tissue. In both in vitro and in vivo gene expression studies PAWE up-regulates pro-apoptotic genes (Bax, Caspases 3, 8 and 9) and down- regulates anti-apoptotic genes (Bcl2). PAWE also down regulates inflammatory gene (Cox-2) and angiogenic gene (VEGF). Conclusion: Preliminary phytochemical screening revealed that PAWE contains various secondary metabolites which contribute to its antioxidant and free radical scavenging property as evaluated by DPPH, FRAP and Iron chelating assay. PAWE exhibits anti-proliferative activity by the induction of apoptosis through a signaling cascade of death receptor-mediated extrinsic (Caspase8 and Tnf-α), as well as mitochondria-mediated intrinsic (caspase9) and caspase pathways (Caspase3, 8 and 9) and also by regressing angiogenic factor (VEGF) without any inflammation or adverse side effects. Hence, PAWE serve as a potential antioxidant and antitumor agent.

Keywords: antioxidant, antitumor, Dalton lymphoma ascites (DLA), fungi, Phellinus robinae

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Authors: Joseph M. Rich, Vinay A. Duddalwar, Assad A. Oberai

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Prostate adenocarcinoma is the most common cancer in males, with osseous metastases as the commonest site of metastatic prostate carcinoma (mPC). Treatment monitoring is based on the evaluation and characterization of lesions on multiple imaging studies, including Computed Tomography (CT). Monitoring of the osseous disease burden, including follow-up of lesions and identification and characterization of new lesions, is a laborious task for radiologists. Deep learning algorithms are increasingly used to perform tasks such as identification and segmentation for osseous metastatic disease and provide accurate information regarding metastatic burden. Here, nnUNet was used to produce a model which can segment CT scan images of prostate adenocarcinoma vertebral bone metastatic lesions. nnUNet is an open-source Python package that adds optimizations to deep learning-based UNet architecture but has not been extensively combined with transfer learning techniques due to the absence of a readily available functionality of this method. The IRB-approved study data set includes imaging studies from patients with mPC who were enrolled in clinical trials at the University of Southern California (USC) Health Science Campus and Los Angeles County (LAC)/USC medical center. Manual segmentation of metastatic lesions was completed by an expert radiologist Dr. Vinay Duddalwar (20+ years in radiology and oncologic imaging), to serve as ground truths for the automated segmentation. Despite nnUNet’s success on some medical segmentation tasks, it only produced an average Dice Similarity Coefficient (DSC) of 0.31 on the USC dataset. DSC results fell in a bimodal distribution, with most scores falling either over 0.66 (reasonably accurate) or at 0 (no lesion detected). Applying more aggressive data augmentation techniques dropped the DSC to 0.15, and reducing the number of epochs reduced the DSC to below 0.1. Datasets have been identified for transfer learning, which involve balancing between size and similarity of the dataset. Identified datasets include the Pancreas data from the Medical Segmentation Decathlon, Pelvic Reference Data, and CT volumes with multiple organ segmentations (CT-ORG). Some of the challenges of producing an accurate model from the USC dataset include small dataset size (115 images), 2D data (as nnUNet generally performs better on 3D data), and the limited amount of public data capturing annotated CT images of bone lesions. Optimizations and improvements will be made by applying transfer learning and generative methods, including incorporating generative adversarial networks and diffusion models in order to augment the dataset. Performance with different libraries, including MONAI and custom architectures with Pytorch, will be compared. In the future, molecular correlations will be tracked with radiologic features for the purpose of multimodal composite biomarker identification. Once validated, these models will be incorporated into evaluation workflows to optimize radiologist evaluation. Our work demonstrates the challenges of applying automated image segmentation to small medical datasets and lays a foundation for techniques to improve performance. As machine learning models become increasingly incorporated into the workflow of radiologists, these findings will help improve the speed and accuracy of vertebral metastatic lesions detection.

Keywords: deep learning, image segmentation, medicine, nnUNet, prostate carcinoma, radiomics

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Authors: Kavita Goel, Donald Winchester

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In a world of information overload and work complexities, academics often struggle to create an online instructional environment enabling efficient and effective student learning. Research has established that students’ learning styles are different, some learn faster when taught using audio and visual methods. Attributes like prior knowledge and mental effort affect their learning. ‘Cognitive load theory’, opines learners have limited processing capacity. Cognitive load depends on the learner’s prior knowledge, the complexity of content and tasks, and instructional environment. Hence, the proper allocation of cognitive resources is critical for students’ learning. Consequently, a lecturer needs to understand the limits and strengths of the human learning processes, various learning styles of students, and accommodate these requirements while designing online assessments. As acknowledged in the cognitive load theory literature, visual and auditory explanations of worked examples potentially lead to a reduction of cognitive load (effort) and increased facilitation of learning when compared to conventional sequential text problem solving. This will help learner to utilize both subcomponents of their working memory. Instructional design changes were introduced at the case site for the delivery of the postgraduate business subjects. To make effective use of auditory and visual modalities, video recorded lectures, and key concept webinars were delivered to students. Videos were prepared to free up student limited working memory from irrelevant mental effort as all elements in a visual screening can be viewed simultaneously, processed quickly, and facilitates greater psychological processing efficiency. Most case study students in the postgraduate programs are adults, working full-time at higher management levels, and studying part-time. Their learning style and needs are different from other tertiary students. The purpose of the audio and visual interventions was to lower the students cognitive load and provide an online environment supportive to their efficient learning. These changes were expected to impact the student’s learning experience, their academic performance and retention favourably. This paper posits that these changes to instruction design facilitates students to integrate new knowledge into their long-term memory. A mixed methods case study methodology was used in this investigation. Primary data were collected from interviews and survey(s) of students and academics. Secondary data were collected from the organisation’s databases and reports. Some evidence was found that the academic performance of students does improve when new instructional design changes are introduced although not statistically significant. However, the overall grade distribution of student’s academic performance has changed and skewed higher which shows deeper understanding of the content. It was identified from feedback received from students that recorded webinars served as better learning aids than material with text alone, especially with more complex content. The recorded webinars on the subject content and assessments provides flexibility to students to access this material any time from repositories, many times, and this enhances students learning style. Visual and audio information enters student’s working memory more effectively. Also as each assessment included the application of the concepts, conceptual knowledge interacted with the pre-existing schema in the long-term memory and lowered student’s cognitive load.

Keywords: cognitive load theory, learning style, instructional environment, working memory

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Authors: Asma'u Mahe, Abdullahi A. Imam, Adamu J. Alhassan, Nasiru Abdullahi, Sadiya A. Bichi, Nura Lawal, Kamaluddeen Babagana

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Malaria is a disease with global health significance. It is caused by parasites and transmitted by Anopheles mosquitoes. Increase in insecticide resistance threatens the disease vector control. The strength of selection pressure acting on a mosquito population in relation to insecticide resistance can be assess by determining the genetic diversity of a fragment spanning exon- 20 of IIS6 of the voltage gated sodium channel (VGSC). Larval samples reared to adulthood were identified and kdr (knock down resistance) profile was determined. The DNA sequences were used to assess the patterns of genetic differentiation by determining the levels of genetic variability between the Anopheles mosquitoes. Genetic differentiation of the Anopheles mosquitoes based on a portion of the voltage gated sodium channel gene was obtained. Polymorphisms were detected; sequence variation and analysis were presented as a phylogenetic tree. Phylogenetic tree of VGSC haplotypes was constructed for samples of the Anopheles mosquitoes using the maximum likelihood method in MEGA 6.0 software. DNA sequences were edited using BioEdit sequence editor. The edited sequences were aligned with reference sequence (Kisumu strain). Analyses were performed as contained in dnaSP 5.10. Results of genetic parameters of polymorphism and haplotype reconstruction were presented in count. Twenty sequences were used for the analysis. Regions selected were 1- 576, invariable (monomorphic) sites were 460 while variable (polymorphic) sites were 5 giving the number of total mutations observed in this study. Mutations obtained from the study were at codon 105: TTC- Phenylalanine replaces TCC- Serine, codon 513: TAG- Termination replaces TTG- Leucine, codon 153, 300 and 553 mutations were non-synonymous. From the constructed phylogenetic tree, some groups were shown to be closer with Exon20Gambiae Kisumu (Reference strain) having some genetic distance, while 5-Exon20Gambiae-F I13.ab1, 18-Exon20Gambiae-F C17.ab1, and 2-Exon20Gambiae-F C13.ab1 clustered together genetically differentiated away from others. Mutations observed in this study can be attributed to the high insecticide resistance profile recorded in the study areas. Haplotype networks of pattern of genetic variability and polymorphism for the fragment of the VGSC sequences of sampled Anopheles mosquitoes revealed low haplotypes for the present study. Haplotypes are set of closely linked DNA variation on X-chromosome. Haplotypes were scaled accordingly to reflect their respective frequencies. Low haplotype number, four VGSC-1014F haplotypes were observed in this study. A positive association was previously established between low haplotype number of VGSC diversity and pyrethroid resistance through kdr mechanism. Significant values at (P < 0.05) of Tajima D and Fu and Li D’ were observed for some of the results indicating possible signature of positive selection on the fragment of VGSC in the study. This is the first report of VGSC-1014F in the study site. Based on the results, the mutation was present in low frequencies. However, the roles played by the observed mutations need further investigation. Mutations, environmental factors among others can affect genetic diversity. The study area has recorded increase in insecticide resistance that can affect vector control in the area. This finding might affect the efforts made against malaria. Sequences were deposited in GenBank for Accession Number.

Keywords: anopheles mosquitoes, insecticide resistance, kdr, malaria, voltage gated sodium channel

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Authors: Keroles Akram Saed Ghatas

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The political violence that characterized 1992 continued into 1993, creating a major security crisis for President Hosni Mubarak's government as the death toll and human rights abuses soared. Increasingly sensitive to criticism of 's human rights activities, the government established human rights departments in key ministries, beginning with the Foreign Office in February. Similar offices have been set up in the Justice and Agriculture Ministries, and plans to set up an office in the Home Office have been announced. It turned out that the main task of the law unit was to overturn the conclusions of international human rights organizations.President Mubarak was elected in a national referendum on October 4 for a third six-year term after being appointed on July 21 by the People's Assembly, an elected parliament overwhelmingly dominated by the in-power National Democratic Party will Mr. Mubarak ran unhindered. The Interior Ministry announced that nearly 16 million people cast their votes (84% of eligible voters), of which 96.28%. voted for presidential re-election.In 1993, armed Islamic extremists escalated their attacks on Christian citizens, government officials, police officers and senior security officials, resulting in casualties among the intended victims and bystanders. Sporadic attacks on buses, boats and tourist attractions also occurred throughout the year. From March 1992 to October 28, 1993, a total of 222 people lost their lives in the riots: 36 Coptic Christians and 38 other citizens; If one is a foreigner; sixty-six members of the Security Forces; and seventy-six known or suspected activists who were killed while resisting arrest. The latter was killed in airstrikes and firefights with security forces and at the site of planned attacks. On March 9-10, a series of airstrikes in Cairo, Giza, Qalyubiya province north of the capital and Aswan killed fifteen suspected militants and five members of the security forces.One of the airstrikes in Giza, part of Greater Cairo, killed the wife and son of Khalifa Mahmoud Ramadan, a suspected militant who was himself killed. The government agency Middle East News Agency reported on March 10 that the raids were part of a "broad confrontational plan aimed at ofterrorist elements"The state of emergency declared in October 1981 after the assassination of President Anwar el-Sadat was still in force in Egypt. The law, previously in effect continuously from June 1967 to May 1980, continued to grant the executive branch unique legal powers that effectively overrode the human rights guarantees of the Egyptian constitution. These provisions included wide discretionary powers in arresting and detaining individuals, as well as the ability to try civilians in military courts. The Cairo-based Independent Organization for Human Rights said so in a document sent to the United Nations in July 1993The human rights committee said the continued imposition of the state of emergency had resulted in "another constitution for the country" and "led to widespread misconduct by the security apparatus".

Keywords: constitution, human rights, legal power, president, anwar, el-sadat, assassination, state of emergency, middle east, news, agency, confrontational, arresting, fugitive, leaders, terrorist, elements, armed islamic extremists.

Procedia PDF Downloads 46