Search results for: real-world data
Commenced in January 2007
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Paper Count: 25117

Search results for: real-world data

307 Role of Functional Divergence in Specific Inhibitor Design: Using γ-Glutamyltranspeptidase (GGT) as a Model Protein

Authors: Ved Vrat Verma, Rani Gupta, Manisha Goel

Abstract:

γ-glutamyltranspeptidase (GGT: EC 2.3.2.2) is an N-terminal nucleophile hydrolase conserved in all three domains of life. GGT plays a key role in glutathione metabolism where it catalyzes the breakage of the γ-glutamyl bonds and transfer of γ-glutamyl group to water (hydrolytic activity) or amino acids or short peptides (transpeptidase activity). GGTs from bacteria, archaea, and eukaryotes (human, rat and mouse) are homologous proteins sharing >50% sequence similarity and conserved four layered αββα sandwich like three dimensional structural fold. These proteins though similar in their structure to each other, are quite diverse in their enzyme activity: some GGTs are better at hydrolysis reactions but poor in transpeptidase activity, whereas many others may show opposite behaviour. GGT is known to be involved in various diseases like asthma, parkinson, arthritis, and gastric cancer. Its inhibition prior to chemotherapy treatments has been shown to sensitize tumours to the treatment. Microbial GGT is known to be a virulence factor too, important for the colonization of bacteria in host. However, all known inhibitors (mimics of its native substrate, glutamate) are highly toxic because they interfere with other enzyme pathways. However, a few successful efforts have been reported previously in designing species specific inhibitors. We aim to leverage the diversity seen in GGT family (pathogen vs. eukaryotes) for designing specific inhibitors. Thus, in the present study, we have used DIVERGE software to identify sites in GGT proteins, which are crucial for the functional and structural divergence of these proteins. Since, type II divergence sites vary in clade specific manner, so type II divergent sites were our focus of interest throughout the study. Type II divergent sites were identified for pathogen vs. eukaryotes clusters and sites were marked on clade specific representative structures HpGGT (2QM6) and HmGGT (4ZCG) of pathogen and eukaryotes clade respectively. The crucial divergent sites within 15 A radii of the binding cavity were highlighted, and in-silico mutations were performed on these sites to delineate the role of these sites on the mechanism of catalysis and protein folding. Further, the amino acid network (AAN) analysis was also performed by Cytoscape to delineate assortative mixing for cavity divergent sites which could strengthen our hypothesis. Additionally, molecular dynamics simulations were performed for wild complexes and mutant complexes close to physiological conditions (pH 7.0, 0.1 M ionic strength and 1 atm pressure) and the role of putative divergence sites and structural integrities of the homologous proteins have been analysed. The dynamics data were scrutinized in terms of RMSD, RMSF, non-native H-bonds and salt bridges. The RMSD, RMSF fluctuations of proteins complexes are compared, and the changes at protein ligand binding sites were highlighted. The outcomes of our study highlighted some crucial divergent sites which could be used for novel inhibitors designing in a species-specific manner. Since, for drug development, it is challenging to design novel drug by targeting similar protein which exists in eukaryotes, so this study could set up an initial platform to overcome this challenge and help to deduce the more effective targets for novel drug discovery.

Keywords: γ-glutamyltranspeptidase, divergence, species-specific, drug design

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306 Chemical and Electrochemical Syntheses of Two Organic Components of Ginger

Authors: Adrienn Kiss, Karoly Zauer, Gyorgy Keglevich, Rita Molnarne Bernath

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Ginger (Zingiber officinale) is a perennial plant from Southeast Asia, widely used as a spice, herb, and medicine for many illnesses since its beneficial health effects were observed thousands of years ago. Among the compounds found in ginger, zingerone [4-hydroxy-3- methoxyphenyl-2-butanone] deserves special attention: it has an anti-inflammatory and antispasmodic effect, it can be used in case of diarrheal disease, helps to prevent the formation of blood clots, has antimicrobial properties, and can also play a role in preventing the Alzheimer's disease. Ferulic acid [(E)-3-(4-hydroxy-3-methoxyphenyl)-prop-2-enoic acid] is another cinnamic acid derivative in ginger, which has promising properties. Like many phenolic compounds, ferulic acid is also an antioxidant. Based on the results of animal experiments, it is assumed to have a direct antitumoral effect in lung and liver cancer. It also deactivates free radicals that can damage the cell membrane and the DNA and helps to protect the skin against UV radiation. The aim of this work was to synthesize these two compounds by new methods. A few of the reactions were based on the hydrogenation of dehydrozingerone [4-(4-Hydroxy-3-methoxyphenyl)-3-buten-2-one] to zingerone. Dehydrozingerone can be synthesized by a relatively simple method from acetone and vanillin with good yield (80%, melting point: 41 °C). Hydrogenation can be carried out chemically, for example by the reaction of zinc and acetic acid, or Grignard magnesium and ethyl alcohol. Another way to complete the reduction is the electrochemical pathway. The electrolysis of dehydrozingerone without diaphragm in aqueous media was attempted to produce ferulic acid in the presence of sodium carbonate and potassium iodide using platinum electrodes. The electrolysis of dehydrozingerone in the presence of potassium carbonate and acetic acid to prepare zingerone was carried out similarly. Ferulic acid was expected to be converted to dihydroferulic acid [3-(4-Hydroxy-3-methoxyphenyl)propanoic acid] in potassium hydroxide solution using iron electrodes, separating the anode and cathode space with a Soxhlet paper sheath impregnated with saturated magnesium chloride solution. For this reaction, ferulic acid was synthesized from vanillin and malonic acid in the presence of pyridine and piperidine (yield: 88.7%, melting point: 173°C). Unfortunately, in many cases, the expected transformations did not happen or took place in low conversions, although gas evolution occurred. Thus, a deeper understanding of these experiments and optimization are needed. Since both compounds are found in different plants, they can also be obtained by alkaline extraction or steam distillation from distinct plant parts (ferulic acid from ground bamboo shoots, zingerone from grated ginger root). The products of these reactions are rich in several other organic compounds as well; therefore, their separation must be solved to get the desired pure material. The products of the reactions described above were characterized by infrared spectral data and melting points. The use of these two simple methods may be informative for the formation of the products. In the future, we would like to study the ferulic acid and zingerone content of other plants and extract them efficiently. The optimization of electrochemical reactions and the use of other test methods are also among our plans.

Keywords: ferulic acid, ginger, synthesis, zingerone

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305 Capturing Healthcare Expert’s Knowledge Digitally: A Scoping Review of Current Approaches

Authors: Sinead Impey, Gaye Stephens, Declan O’Sullivan

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Mitigating organisational knowledge loss presents challenges for knowledge managers. Expert knowledge is embodied in people and captured in ‘routines, processes, practices and norms’ as well as in the paper system. These knowledge stores have limitations in so far as they make knowledge diffusion beyond geography or over time difficult. However, technology could present a potential solution by facilitating the capture and management of expert knowledge in a codified and sharable format. Before it can be digitised, however, the knowledge of healthcare experts must be captured. Methods: As a first step in a larger project on this topic, a scoping review was conducted to identify how expert healthcare knowledge is captured digitally. The aim of the review was to identify current healthcare knowledge capture practices, identify gaps in the literature, and justify future research. The review followed a scoping review framework. From an initial 3,430 papers retrieved, 22 were deemed relevant and included in the review. Findings: Two broad approaches –direct and indirect- with themes and subthemes emerged. ‘Direct’ describes a process whereby knowledge is taken directly from subject experts. The themes identified were: ‘Researcher mediated capture’ and ‘Digital mediated capture’. The latter was further distilled into two sub-themes: ‘Captured in specified purpose platforms (SPP)’ and ‘Captured in a virtual community of practice (vCoP)’. ‘Indirect’ processes rely on extracting new knowledge using artificial intelligence techniques from previously captured data. Using this approach, the theme ‘Generated using artificial intelligence methods’ was identified. Although presented as distinct themes, some papers retrieved discuss combining more than one approach to capture knowledge. While no approach emerged as superior, two points arose from the literature. Firstly, human input was evident across themes, even with indirect approaches. Secondly, a range of challenges common among approaches was highlighted. These were (i) ‘Capturing an expert’s knowledge’- Difficulties surrounding capturing an expert’s knowledge related to identifying the ‘expert’ say from the very experienced and how to capture their tacit or difficult to articulate knowledge. (ii) ‘Confirming quality of knowledge’- Once captured, challenges noted surrounded how to validate knowledge captured and, therefore, quality. (iii) ‘Continual knowledge capture’- Once knowledge is captured, validated, and used in a system; however, the process is not complete. Healthcare is a knowledge-rich environment with new evidence emerging frequently. As such, knowledge needs to be reviewed, updated, or removed (redundancy) as appropriate. Although some methods were proposed to address this, such as plausible reasoning or case-based reasoning, conclusions could not be drawn from the papers retrieved. It was, therefore, highlighted as an area for future research. Conclusion: The results described two broad approaches – direct and indirect. Three themes were identified: ‘Researcher mediated capture (Direct)’; ‘Digital mediated capture (Direct)’ and ‘Generated using artificial intelligence methods (Indirect)’. While no single approach was deemed superior, common challenges noted among approaches were: ‘capturing an expert’s knowledge’, ‘confirming quality of knowledge’, and ‘continual knowledge capture’. However, continual knowledge capture was not fully explored in the papers retrieved and was highlighted as an important area for future research. Acknowledgments: This research is partially funded by the ADAPT Centre under the SFI Research Centres Programme (Grant 13/RC/2106) and is co-funded under the European Regional Development Fund.

Keywords: expert knowledge, healthcare, knowledge capture and knowledge management

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304 Opportunities in Self-care Abortion and Telemedicine: Findings from a Study in Colombia

Authors: Paola Montenegro, Maria de los Angeles Balaguera Villa

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In February 2022 Colombia achieved a historic milestone in ensuring universal access to abortion rights with ruling C-055 of 2022 decriminalising abortion up to 24 weeks of gestation. In the context of this triumph and the expansion of telemedicine services in the wake of the COVID-19 pandemic, this research studied the acceptability of self-care abortion in young people (13 - 28 years) through a telemedicine service and also explored the primary needs that should be the focus of such care. The results shine light on a more comprehensive understanding of opportunities and challenges of teleabortion practices in a context that combines overall higher access to technology and low access to reliable information of safe abortion, stigma, and scarcity especially felt by transnational migrants, racialised people, trans men and non-binary people. Through a mixed methods approach, this study collected 5.736 responses to a virtual survey disseminated nationwide in Colombia and 47 in-person interviews (24 of them with people who were assigned female at birth and 21 with local key stakeholders in the abortion ecosystem). Quantitative data was analyzed using Stata SE Version 16.0 and qualitative analysis was completed through NVivo using thematic analysis. Key findings of the research suggest that self-care abortion is practice with growing acceptability among young people, but important adjustments must be made to meet quality of care expectations of users. Elements like quick responses from providers, lower costs, and accessible information were defined by users as decisive factors to choose over the abortion service provider. In general, the narratives in participants about quality care were centred on the promotion of autonomy and the provision of accompaniment and care practices, also perceived as transformative and currently absent of most health care services. The most staggering findings from the investigation are related to current barriers faced by young people in abortion contexts even when the legal barriers have: high rates of scepticism and distrust associated with pitfalls of telehealth and structural challenges associated with lacking communications infrastructure, among a few of them. Other important barriers to safe self-care abortion identified by participants surfaced like lack of privacy and confidentiality (especially in rural areas of the country), difficulties accessing reliable information, high costs of procedures and expenses related to travel costs or having to cease economic activities, waiting times, and stigma are among the primary barriers to abortion identified by participants. Especially in a scenario marked by unprecedented social, political and economic disruptions due to the COVID-19 pandemic, the commitment to design better care services that can be adapted to the identities, experiences, social contexts and possibilities of the user population is more necessary than ever. In this sense, the possibility of expanding access to services through telemedicine brings us closer to the opportunity to rethink the role of health care models in transforming the role of individuals and communities to make autonomous, safe and informed decisions about their own health and well-being.

Keywords: contraception, family planning, premarital fertility, unplanned pregnancy

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

Authors: Aleksandra Bylinska, Samantha Slight-Webb, Kevin Thomas, Miles Smith, Susan Macwana, Nicolas Dominguez, Eliza Chakravarty, Joan T. Merrill, Judith A. James, Joel M. Guthridge

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Background: Systemic Lupus Erythematosus (SLE) is an interferon-related autoimmune disease characterized by B cell dysfunction. One of the main hallmarks is a loss of tolerance to self-antigens leading to increased levels of autoantibodies against nuclear components (ANAs). However, up to 20% of healthy ANA+ individuals will not develop clinical illness. SLE is more prevalent among women and minority populations (African, Asian American and Hispanics). Moreover, African Americans have a stronger interferon (IFN) signature and develop more severe symptoms. The exact mechanisms involved in ethnicity-dependent B cell dysregulation and the progression of autoimmune disease from ANA+ healthy individuals to clinical disease remains unclear. Methods: Peripheral blood mononuclear cells (PBMCs) from African (AA) and European American (EA) ANA- (n=12), ANA+ (n=12) and SLE (n=12) individuals were assessed by multimodal scRNA-Seq/CITE-Seq methods to examine differential gene signatures in specific B cell subsets. Library preparation was done with a 10X Genomics Chromium according to established protocols and sequenced on Illumina NextSeq. The data were further analyzed for distinct cluster identification and differential gene signatures in the Seurat package in R and pathways analysis was performed using Ingenuity Pathways Analysis (IPA). Results: Comparing all subjects, 14 distinct B cell clusters were identified using a community detection algorithm and visualized with Uniform Manifold Approximation Projection (UMAP). The proportion of each of those clusters varied by disease status and ethnicity. Transitional B cells trended higher in ANA+ healthy individuals, especially in AA. Ribonucleoprotein high population (HNRNPH1 elevated, heterogeneous nuclear ribonucleoprotein, RNP-Hi) of proliferating Naïve B cells were more prevalent in SLE patients, specifically in EA. Interferon-induced protein high population (IFIT-Hi) of Naive B cells are increased in EA ANA- individuals. The proportion of memory B cells and plasma cells clusters tend to be expanded in SLE patients. As anticipated, we observed a higher signature of cytokine-related pathways, especially interferon, in SLE individuals. Pathway analysis among AA individuals revealed an NRF2-mediated Oxidative Stress response signature in the transitional B cell cluster, not seen in EA individuals. TNFR1/2 and Sirtuin Signaling pathway genes were higher in AA IFIT-Hi Naive B cells, whereas they were not detected in EA individuals. Interferon signaling was observed in B cells in both ethnicities. Oxidative phosphorylation was found in age-related B cells (ABCs) for both ethnicities, whereas Death Receptor Signaling was found only in EA patients in these cells. Interferon-related transcription factors were elevated in ABCs and IFIT-Hi Naive B cells in SLE subjects of both ethnicities. Conclusions: ANA+ healthy individuals have altered gene expression pathways in B cells that might drive apoptosis and subsequent clinical autoimmune pathogenesis. Increases in certain regulatory pathways may delay progression to SLE. Further, AA individuals have more elevated activation pathways that may make them more susceptible to SLE.

Keywords:

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302 Influence of Water Physicochemical Properties and Vegetation Type on the Distribution of Schistosomiasis Intermediate Host Snails in Nelson Mandela Bay

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

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

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

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301 Eco-Politics of Infrastructure Development in and Around Protected Areas in Kenya: The Case of Nairobi National Park

Authors: Teresa Wanjiru Mbatia

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On 7th June 2011, the government Minister of Roads in Kenya announced the proposed construction of a major highway known as a southern bypass to run on the northern border of the Nairobi National Park. The following day on 8th June 2011, the chairperson of the Friends of Nairobi National Park (FONNAP) posted a protest statement on their website, with the heading, ‘Nairobi Park is Not a cake’ alerting its members and conservation groups, with the aim of getting support to the campaign against the government’s intention to hive off a section of the park for road construction. This was the first and earliest statement that led to a series of other events that culminated in conservationists and some other members of the public campaign against the government’s plan to hive off sections of the park to build road and railway infrastructure in or around the park. Together with other non-state actors, mostly non-governmental organisations in conservation/environment and tourism businesses, FoNNAP issued a series of other statements on social, print and electronic media to battle against road and railway construction. This paper examined the strategies, outcomes and interests of actors involved in opposing/proposing the development of transport infrastructure in and around the Nairobi National Park. Specifically, the objectives were to analyse the: (1) Arguments put forward by the eco-warriors to protest infrastructure development; (2) Background and interests of the eco-warriors; (3) Needs/interests and opinions of ordinary common citizens on transport infrastructural development, particularly in and around the urban nature reserve and (4) Final outcomes of the eco-politics surrounding infrastructure development in and around Nairobi National Park. The methodological approach used was environmental history and the social construction of nature. The study collected combined qualitative data using four main approaches, the grounded theory approach, narratives, case studies and a phenomenological approach. The information collected was analysed using critical discourse analysis. The major findings of the study were that under the guise of “public participation,” influential non-state actors have the capacity to perpetuate social-spatial inequalities in the form of curtailing the majority from accessing common public goods. A case in point in this study is how the efforts of powerful conservationists, environmentalists, and tourism businesspersons managed to stall the construction of much-needed road and railway infrastructure severally through litigations in lengthy environmental court processes involving injunctions and stop orders to the government bodies in charge. Moreover, powerful non-state actors were found to have formed informal and sometimes formal coalitions with politicians with selfish interests, which serves to deepen the exclusionary practices and the common good. The study concludes that mostly composed of certain types of elites (NGOs, business communities, politicians and privileged social-cultural groups), non-state actors have used participatory policies to advance their own interests at the expense of the majority whom they claim to represent. These practices are traced to the historically unjust social, political, and economic forces involved in the production of space in Nairobi.

Keywords: eco-politics, exclusion, infrastructure, Nairobi national park, non-state actors, protests

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300 Decision Making on Smart Energy Grid Development for Availability and Security of Supply Achievement Using Reliability Merits

Authors: F. Iberraken, R. Medjoudj, D. Aissani

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The development of the smart grids concept is built around two separate definitions, namely: The European one oriented towards sustainable development and the American one oriented towards reliability and security of supply. In this paper, we have investigated reliability merits enabling decision-makers to provide a high quality of service. It is based on system behavior using interruptions and failures modeling and forecasting from one hand and on the contribution of information and communication technologies (ICT) to mitigate catastrophic ones such as blackouts from the other hand. It was found that this concept has been adopted by developing and emerging countries in short and medium terms followed by sustainability concept at long term planning. This work has highlighted the reliability merits such as: Benefits, opportunities, costs and risks considered as consistent units of measuring power customer satisfaction. From the decision making point of view, we have used the analytic hierarchy process (AHP) to achieve customer satisfaction, based on the reliability merits and the contribution of such energy resources. Certainly nowadays, fossil and nuclear ones are dominating energy production but great advances are already made to jump into cleaner ones. It was demonstrated that theses resources are not only environmentally but also economically and socially sustainable. The paper is organized as follows: Section one is devoted to the introduction, where an implicit review of smart grids development is given for the two main concepts (for USA and Europeans countries). The AHP method and the BOCR developments of reliability merits against power customer satisfaction are developed in section two. The benefits where expressed by the high level of availability, maintenance actions applicability and power quality. Opportunities were highlighted by the implementation of ICT in data transfer and processing, the mastering of peak demand control, the decentralization of the production and the power system management in default conditions. Costs were evaluated using cost-benefit analysis, including the investment expenditures in network security, becoming a target to hackers and terrorists, and the profits of operating as decentralized systems, with a reduced energy not supplied, thanks to the availability of storage units issued from renewable resources and to the current power lines (CPL) enabling the power dispatcher to manage optimally the load shedding. For risks, we have razed the adhesion of citizens to contribute financially to the system and to the utility restructuring. What is the degree of their agreement compared to the guarantees proposed by the managers about the information integrity? From technical point of view, have they sufficient information and knowledge to meet a smart home and a smart system? In section three, an application of AHP method is made to achieve power customer satisfaction based on the main energy resources as alternatives, using knowledge issued from a country that has a great advance in energy mutation. Results and discussions are given in section four. It was given us to conclude that the option to a given resource depends on the attitude of the decision maker (prudent, optimistic or pessimistic), and that status quo is neither sustainable nor satisfactory.

Keywords: reliability, AHP, renewable energy resources, smart grids

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299 An Infrared Inorganic Scintillating Detector Applied in Radiation Therapy

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

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

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

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298 Management of the Experts in the Research Evaluation System of the University: Based on National Research University Higher School of Economics Example

Authors: Alena Nesterenko, Svetlana Petrikova

Abstract:

Research evaluation is one of the most important elements of self-regulation and development of researchers as it is impartial and independent process of assessment. The method of expert evaluations as a scientific instrument solving complicated non-formalized problems is firstly a scientifically sound way to conduct the assessment which maximum effectiveness of work at every step and secondly the usage of quantitative methods for evaluation, assessment of expert opinion and collective processing of the results. These two features distinguish the method of expert evaluations from long-known expertise widespread in many areas of knowledge. Different typical problems require different types of expert evaluations methods. Several issues which arise with these methods are experts’ selection, management of assessment procedure, proceeding of the results and remuneration for the experts. To address these issues an on-line system was created with the primary purpose of development of a versatile application for many workgroups with matching approaches to scientific work management. Online documentation assessment and statistics system allows: - To realize within one platform independent activities of different workgroups (e.g. expert officers, managers). - To establish different workspaces for corresponding workgroups where custom users database can be created according to particular needs. - To form for each workgroup required output documents. - To configure information gathering for each workgroup (forms of assessment, tests, inventories). - To create and operate personal databases of remote users. - To set up automatic notification through e-mail. The next stage is development of quantitative and qualitative criteria to form a database of experts. The inventory was made so that the experts may not only submit their personal data, place of work and scientific degree but also keywords according to their expertise, academic interests, ORCID, Researcher ID, SPIN-code RSCI, Scopus AuthorID, knowledge of languages, primary scientific publications. For each project, competition assessments are processed in accordance to ordering party demands in forms of apprised inventories, commentaries (50-250 characters) and overall review (1500 characters) in which expert states the absence of conflict of interest. Evaluation is conducted as follows: as applications are added to database expert officer selects experts, generally, two persons per application. Experts are selected according to the keywords; this method proved to be good unlike the OECD classifier. The last stage: the choice of the experts is approved by the supervisor, the e-mails are sent to the experts with invitation to assess the project. An expert supervisor is controlling experts writing reports for all formalities to be in place (time-frame, propriety, correspondence). If the difference in assessment exceeds four points, the third evaluation is appointed. As the expert finishes work on his expert opinion, system shows contract marked ‘new’, managers commence with the contract and the expert gets e-mail that the contract is formed and ready to be signed. All formalities are concluded and the expert gets remuneration for his work. The specificity of interaction of the examination officer with other experts will be presented in the report.

Keywords: expertise, management of research evaluation, method of expert evaluations, research evaluation

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

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

Abstract:

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

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

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296 Poly (3,4-Ethylenedioxythiophene) Prepared by Vapor Phase Polymerization for Stimuli-Responsive Ion-Exchange Drug Delivery

Authors: M. Naveed Yasin, Robert Brooke, Andrew Chan, Geoffrey I. N. Waterhouse, Drew Evans, Darren Svirskis, Ilva D. Rupenthal

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Poly(3,4-ethylenedioxythiophene) (PEDOT) is a robust conducting polymer (CP) exhibiting high conductivity and environmental stability. It can be synthesized by either chemical, electrochemical or vapour phase polymerization (VPP). Dexamethasone sodium phosphate (dexP) is an anionic drug molecule which has previously been loaded onto PEDOT as a dopant via electrochemical polymerisation; however this technique requires conductive surfaces from which polymerization is initiated. On the other hand, VPP produces highly organized biocompatible CP structures while polymerization can be achieved onto a range of surfaces with a relatively straight forward scale-up process. Following VPP of PEDOT, dexP can be loaded and subsequently released via ion-exchange. This study aimed at preparing and characterising both non-porous and porous VPP PEDOT structures including examining drug loading and release via ion-exchange. Porous PEDOT structures were prepared by first depositing a sacrificial polystyrene (PS) colloidal template on a substrate, heat curing this deposition and then spin coating it with the oxidant solution (iron tosylate) at 1500 rpm for 20 sec. VPP of both porous and non-porous PEDOT was achieved by exposing to monomer vapours in a vacuum oven at 40 mbar and 40 °C for 3 hrs. Non-porous structures were prepared similarly on the same substrate but without any sacrificial template. Surface morphology, compositions and behaviour were then characterized by atomic force microscopy (AFM), scanning electron microscopy (SEM), x-ray photoelectron spectroscopy (XPS) and cyclic voltammetry (CV) respectively. Drug loading was achieved by 50 CV cycles in a 0.1 M dexP aqueous solution. For drug release, each sample was exposed to 20 mL of phosphate buffer saline (PBS) placed in a water bath operating at 37 °C and 100 rpm. Film was stimulated (continuous pulse of ± 1 V at 0.5 Hz for 17 mins) while immersed into PBS. Samples were collected at 1, 2, 6, 23, 24, 26 and 27 hrs and were analysed for dexP by high performance liquid chromatography (HPLC Agilent 1200 series). AFM and SEM revealed the honey comb nature of prepared porous structures. XPS data showed the elemental composition of the dexP loaded film surface, which related well with that of PEDOT and also showed that one dexP molecule was present per almost three EDOT monomer units. The reproducible electroactive nature was shown by several cycles of reduction and oxidation via CV. Drug release revealed success in drug loading via ion-exchange, with stimulated porous and non-porous structures exhibiting a proof of concept burst release upon application of an electrical stimulus. A similar drug release pattern was observed for porous and non-porous structures without any significant statistical difference, possibly due to the thin nature of these structures. To our knowledge, this is the first report to explore the potential of VPP prepared PEDOT for stimuli-responsive drug delivery via ion-exchange. The produced porous structures were ordered and highly porous as indicated by AFM and SEM. These porous structures exhibited good electroactivity as shown by CV. Future work will investigate porous structures as nano-reservoirs to increase drug loading while sealing these structures to minimize spontaneous drug leakage.

Keywords: PEDOT for ion-exchange drug delivery, stimuli-responsive drug delivery, template based porous PEDOT structures, vapour phase polymerization of PEDOT

Procedia PDF Downloads 231
295 A Simulation Study of Direct Injection Compressed Natural Gas Spark Ignition Engine Performance Utilizing Turbulent Jet Ignition with Controlled Air Charge

Authors: Siyamak Ziyaei, Siti Khalijah Mazlan, Petros Lappas

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Compressed Natural Gas (CNG) mainly consists of Methane CH₄ and has a low carbon to hydrogen ratio relative to other hydrocarbons. As a result, it has the potential to reduce CO₂ emissions by more than 20% relative to conventional fuels like diesel or gasoline Although Natural Gas (NG) has environmental advantages compared to other hydrocarbon fuels whether they are gaseous or liquid, its main component, CH₄, burns at a slower rate than conventional fuels A higher pressure and a leaner cylinder environment will overemphasize slow burn characteristic of CH₄. Lean combustion and high compression ratios are well-known methods for increasing the efficiency of internal combustion engines. In order to achieve successful CNG lean combustion in Spark Ignition (SI) engines, a strong ignition system is essential to avoid engine misfires, especially in ultra-lean conditions. Turbulent Jet Ignition (TJI) is an ignition system that employs a pre-combustion chamber to ignite the lean fuel mixture in the main combustion chamber using a fraction of the total fuel per cycle. TJI enables ultra-lean combustion by providing distributed ignition sites through orifices. The fast burn rate provided by TJI enables the ordinary SI engine to be comparable to other combustion systems such as Homogeneous Charge Compression Ignition (HCCI) or Controlled Auto-Ignition (CAI) in terms of thermal efficiency, through the increased levels of dilution without the need of sophisticated control systems. Due to the physical geometry of TJIs, which contain small orifices that connect the prechamber to the main chamber, scavenging is one of the main factors that reduce TJI performance. Specifically, providing the right mixture of fuel and air has been identified as a key challenge. The reason for this is the insufficient amount of air that is pushed into the pre-chamber during each compression stroke. There is also the problem that combustion residual gases such as CO₂, CO and NOx from the previous combustion cycle dilute the pre- chamber fuel-air mixture preventing rapid combustion in the pre-chamber. An air-controlled active TJI is presented in this paper in order to address these issues. By applying air to the pre-chamber at a sufficient pressure, residual gases are exhausted, and the air-fuel ratio is controlled within the pre-chamber, thereby improving the quality of combustion. This paper investigates the 3D-simulated combustion characteristics of a Direct Injected (DI-CNG) fuelled SI en- gine with a pre-chamber equipped with an air channel by using AVL FIRE software. Experiments and simulations were performed at the Worldwide Mapping Point (WWMP) at 1500 Revolutions Per Minute (RPM), 3.3 bar Indicated Mean Effective Pressure (IMEP), using only conventional spark plugs as the baseline. After validating simulation data, baseline engine conditions were set for all simulation scenarios at λ=1. Following that, the pre-chambers with and without an auxiliary fuel supply were simulated. In the simulated (DI-CNG) SI engine, active TJI was observed to perform better than passive TJI and spark plug. In conclusion, the active pre-chamber with an air channel demon-strated an improved thermal efficiency (ηth) over other counterparts and conventional spark ignition systems.

Keywords: turbulent jet ignition, active air control turbulent jet ignition, pre-chamber ignition system, active and passive pre-chamber, thermal efficiency, methane combustion, internal combustion engine combustion emissions

Procedia PDF Downloads 87
294 Plasma Levels of Collagen Triple Helix Repeat Containing 1 (CTHRC1) as a Potential Biomarker in Interstitial Lung Disease

Authors: Rijnbout-St.James Willem, Lindner Volkhard, Scholand Mary Beth, Ashton M. Tillett, Di Gennaro Michael Jude, Smith Silvia Enrica

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Introduction: Fibrosing lung diseases are characterized by changes in the lung interstitium and are classified based on etiology: 1) environmental/exposure-related, 2) autoimmune-related, 3) sarcoidosis, 4) interstitial pneumonia, and 4) idiopathic. Among interstitial lung diseases (ILD) idiopathic forms, idiopathic pulmonary fibrosis (IPF) is the most severe. Pathogenesis of IPF is characterized by an increased presence of proinflammatory mediators, resulting in alveolar injury, where injury to alveolar epithelium precipitates an increase in collagen deposition, subsequently thickening the alveolar septum and decreasing gas exchange. Identifying biomarkers implicated in the pathogenesis of lung fibrosis is key to developing new therapies and improving the efficacy of existing therapies. The transforming growth factor-beta (TGF-B1), a mediator of tissue repair associated with WNT5A signaling, is partially responsible for fibroblast proliferation in ILD and is the target of Pirfenidone, one of the antifibrotic therapies used for patients with IPF. Canonical TGF-B signaling is mediated by the proteins SMAD 2/3, which are, in turn, indirectly regulated by Collagen Triple Helix Repeat Containing 1 (CTHRC1). In this study, we tested the following hypotheses: 1) CTHRC1 is more elevated in the ILD cohort compared to unaffected controls, and 2) CTHRC1 is differently expressed among ILD types. Material and Methods: CTHRC1 levels were measured by ELISA in 171 plasma samples from the deidentified University of Utah ILD cohort. Data represent a cohort of 131 ILD-affected participants and 40 unaffected controls. CTHRC1 samples were categorized by a pulmonologist based on affectation status and disease subtypes: IPF (n = 45), sarcoidosis (4), nonspecific interstitial pneumonia (16), hypersensitivity pneumonitis (n = 7), interstitial pneumonia (n=13), autoimmune (n = 15), other ILD - a category that includes undifferentiated ILD diagnoses (n = 31), and unaffected controls (n = 40). We conducted a single-factor ANOVA of plasma CTHRC1 levels to test whether CTHRC1 variance among affected and non-affected participants is statistically significantly different. In-silico analysis was performed with Ingenuity Pathway Analysis® to characterize the role of CTHRC1 in the pathway of lung fibrosis. Results: Statistical analyses of CTHRC1 in plasma samples indicate that the average CTHRC1 level is significantly higher in ILD-affected participants than controls, with the autoimmune ILD being higher than other ILD types, thus supporting our hypotheses. In-silico analyses show that CTHRC1 indirectly activates and phosphorylates SMAD3, which in turn cross-regulates TGF-B1. CTHRC1 also may regulate the expression and transcription of TGFB-1 via WNT5A and its regulatory relationship with CTNNB1. Conclusion: In-silico pathway analyses demonstrate that CTHRC1 may be an important biomarker in ILD. Analysis of plasma samples indicates that CTHRC1 expression is positively associated with ILD affectation, with autoimmune ILD having the highest average CTHRC1 values. While characterizing CTHRC1 levels in plasma can help to differentiate among ILD types and predict response to Pirfenidone, the extent to which plasma CTHRC1 level is a function of ILD severity or chronicity is unknown.

Keywords: interstitial lung disease, CTHRC1, idiopathic pulmonary fibrosis, pathway analyses

Procedia PDF Downloads 191
293 The Impact of the Media in the Implementation of Qatar’s Foreign Policy on the Public Opinion of the People of the Middle East (2011-2023)

Authors: Negar Vkilbashi, Hassan Kabiri

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Modern diplomacy, in its general form, refers to the people and not the governments, and diplomacy tactics are more addressed to the people than to the governments. Media diplomacy and cyber diplomacy are also one of the sub-branches of public diplomacy and, in fact, the role of media in the process of influencing public opinion and directing foreign policy. Mass media, including written, radio and television, theater, satellite, internet, and news agencies, transmit information and demands. What the Qatari government tried to implement in the countries of the region during the Arab Spring and after was through its important media, Al Jazeera. The embargo on Qatar began in 2017, when Saudi Arabia, the United Arab Emirates, Bahrain, and Egypt imposed a land, sea, and air blockade against the country. The media tool constitutes the cornerstone of soft power in the field of foreign policy, which Qatari leaders have consistently resorted to over the past two decades. Undoubtedly, the role it played in covering the events of the Arab Spring has created geopolitical tensions. The United Arab Emirates and other neighboring countries sometimes criticize Al Jazeera for providing a platform for the Muslim Brotherhood, Hamas, and other Islamists to promote their ideology. In 2011, at the same time as the Arab Spring, Al Jazeera reached the peak of its popularity. Al Jazeera's live coverage of protests in Tunisia, Egypt, Yemen, Libya, and Syria helped create a unified narrative of the Arab Spring, with audiences tuning in every Friday to watch simultaneous protests across the Middle East. Al Jazeera operates in three groups: First, it is a powerful base in the hands of the government so that it can direct and influence Arab public opinion. Therefore, this network has been able to benefit from the unlimited financial support of the Qatar government to promote its desired policies and culture. Second, it has provided an attractive platform for politicians and scientific and intellectual elites, thus attracting their support and defense from the government and its rulers. Third, during the last years of Prince Hamad's reign, the Al Jazeera network formed a deterrent weapon to counter the media and political struggle campaigns. The importance of the research is that this network covers a wide range of people in the Middle East and, therefore, has a high influence on the decision-making of countries. On the other hand, Al Jazeera is influential as a tool of public diplomacy and soft power in Qatar's foreign policy, and by studying it, the results of its effectiveness in the past years can be examined. Using a qualitative method, this research analyzes the impact of the media on the implementation of Qatar's foreign policy on the public opinion of the people of the Middle East. Data collection has been done by the secondary method, that is, reading related books, magazine articles, newspaper reports and articles, and analytical reports of think tanks. The most important findings of the research are that Al Jazeera plays an important role in Qatar's foreign policy in Qatar's public diplomacy. So that, in 2011, 2017 and 2023, it played an important role in Qatar's foreign policy in various crises. Also, the people of Arab countries use Al-Jazeera as their first reference.

Keywords: Al Jazeera, Qatar, media, diplomacy

Procedia PDF Downloads 78
292 Antibiotic Prophylaxis Habits in Oral Implant Surgery in the Netherlands: A Cross-Sectional Survey

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

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

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

Procedia PDF Downloads 141
291 Effects and Mechanisms of an Online Short-Term Audio-Based Mindfulness Intervention on Wellbeing in Community Settings and How Stress and Negative Affect Influence the Therapy Effects: Parallel Process Latent Growth Curve Modeling of a Randomized Control

Authors: Man Ying Kang, Joshua Kin Man Nan

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The prolonged pandemic has posed alarming public health challenges to various parts of the world, and face-to-face mental health treatment is largely discounted for the control of virus transmission, online psychological services and self-help mental health kits have become essential. Online self-help mindfulness-based interventions have proved their effects on fostering mental health for different populations over the globe. This paper was to test the effectiveness of an online short-term audio-based mindfulness (SAM) program in enhancing wellbeing, dispositional mindfulness, and reducing stress and negative affect in community settings in China, and to explore possible mechanisms of how dispositional mindfulness, stress, and negative affect influenced the intervention effects on wellbeing. Community-dwelling adults were recruited via online social networking sites (e.g., QQ, WeChat, and Weibo). Participants (n=100) were randomized into the mindfulness group (n=50) and a waitlist control group (n=50). In the mindfulness group, participants were advised to spend 10–20 minutes listening to the audio content, including mindful-form practices (e.g., eating, sitting, walking, or breathing). Then practice daily mindfulness exercises for 3 weeks (a total of 21 sessions), whereas those in the control group received the same intervention after data collection in the mindfulness group. Participants in the mindfulness group needed to fill in the World Health Organization Five Well-Being Index (WHO), Positive and Negative Affect Schedule (PANAS), Perceived Stress Scale (PSS), and Freiburg Mindfulness Inventory (FMI) four times: at baseline (T0) and at 1 (T1), 2 (T2), and 3 (T3) weeks while those in the waitlist control group only needed to fill in the same scales at pre- and post-interventions. Repeated-measure analysis of variance, paired sample t-test, and independent sample t-test was used to analyze the variable outcomes of the two groups. The parallel process latent growth curve modeling analysis was used to explore the longitudinal moderated mediation effects. The dependent variable was WHO slope from T0 to T3, the independent variable was Group (1=SAM, 2=Control), the mediator was FMI slope from T0 to T3, and the moderator was T0NA and T0PSS separately. The different levels of moderator effects on WHO slope was explored, including low T0NA or T0PSS (Mean-SD), medium T0NA or T0PSS (Mean), and high T0NA or T0PSS (Mean+SD). The results found that SAM significantly improved and predicted higher levels of WHO slope and FMI slope, as well as significantly reduced NA and PSS. FMI slope positively predict WHO slope. FMI slope partially mediated the relationship between SAM and WHO slope. Baseline NA and PSS as the moderators were found to be significant between SAM and WHO slope and between SAM and FMI slope, respectively. The conclusion was that SAM was effective in promoting levels of mental wellbeing, positive affect, and dispositional mindfulness as well as reducing negative affect and stress in community settings in China. SAM improved wellbeing faster through the faster enhancement of dispositional mindfulness. Participants with medium-to-high negative affect and stress buffered the therapy effects of SAM on wellbeing improvement speed.

Keywords: mindfulness, negative affect, stress, wellbeing, randomized control trial

Procedia PDF Downloads 109
290 Rheological and Microstructural Characterization of Concentrated Emulsions Prepared by Fish Gelatin

Authors: Helen S. Joyner (Melito), Mohammad Anvari

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Concentrated emulsions stabilized by proteins are systems of great importance in food, pharmaceutical and cosmetic products. Controlling emulsion rheology is critical for ensuring desired properties during formation, storage, and consumption of emulsion-based products. Studies on concentrated emulsions have focused on rheology of monodispersed systems. However, emulsions used for industrial applications are polydispersed in nature, and this polydispersity is regarded as an important parameter that also governs the rheology of the concentrated emulsions. Therefore, the objective of this study was to characterize rheological (small and large deformation behaviors) and microstructural properties of concentrated emulsions which were not truly monodispersed as usually encountered in food products such as margarines, mayonnaise, creams, spreads, and etc. The concentrated emulsions were prepared at different concentrations of fish gelatin (0.2, 0.4, 0.8% w/v in the whole emulsion system), oil-water ratio 80-20 (w/w), homogenization speed 10000 rpm, and 25oC. Confocal laser scanning microscopy (CLSM) was used to determine the microstructure of the emulsions. To prepare samples for CLSM analysis, FG solutions were stained by Fluorescein isothiocyanate dye. Emulsion viscosity profiles were determined using shear rate sweeps (0.01 to 100 1/s). The linear viscoelastic regions (LVRs) of the emulsions were determined using strain sweeps (0.01 to 100% strain) for each sample. Frequency sweeps were performed in the LVR (0.1% strain) from 0.6 to 100 rad/s. Large amplitude oscillatory shear (LAOS) testing was conducted by collecting raw waveform data at 0.05, 1, 10, and 100% strain at 4 different frequencies (0.5, 1, 10, and 100 rad/s). All measurements were performed in triplicate at 25oC. The CLSM results revealed that increased fish gelatin concentration resulted in more stable oil-in-water emulsions with homogeneous, finely dispersed oil droplets. Furthermore, the protein concentration had a significant effect on emulsion rheological properties. Apparent viscosity and dynamic moduli at small deformations increased with increasing fish gelatin concentration. These results were related to increased inter-droplet network connections caused by increased fish gelatin adsorption at the surface of oil droplets. Nevertheless, all samples showed shear-thinning and weak gel behaviors over shear rate and frequency sweeps, respectively. Lissajous plots, or plots of stress versus strain, and phase lag values were used to determine nonlinear behavior of the emulsions in LAOS testing. Greater distortion in the elliptical shape of the plots followed by higher phase lag values was observed at large strains and frequencies in all samples, indicating increased nonlinear behavior. Shifts from elastic-dominated to viscous dominated behavior were also observed. These shifts were attributed to damage to the sample microstructure (e.g. gel network disruption), which would lead to viscous-type behaviors such as permanent deformation and flow. Unlike the small deformation results, the LAOS behavior of the concentrated emulsions was not dependent on fish gelatin concentration. Systems with different microstructures showed similar nonlinear viscoelastic behaviors. The results of this study provided valuable information that can be used to incorporate concentrated emulsions in emulsion-based food formulations.

Keywords: concentrated emulsion, fish gelatin, microstructure, rheology

Procedia PDF Downloads 275
289 Participation of Titanium Influencing the Petrological Assemblage of Mafic Dyke: Salem, South India

Authors: Ayoti Banerjee, Meenakshi Banerjee

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The study of metamorphic reaction textures is important in contributing to our understanding of the evolution of metamorphic terranes. Where preserved, they provide information on changes in the P-T conditions during the metamorphic history of the rock, and thus allow us to speculate on the P-T-t evolution of the terrane. Mafic dykes have attracted the attention of petrologists because they act as window to mantle. This rock represents a mafic dyke of doleritic composition. It is fine to medium grained in which clinopyroxene are enclosed by the lath shaped plagioclase grains to form spectacular ophitic texture. At places, sub ophitic texture was also observed. Grains of pyroxene and plagioclase show very less deformation typically plagioclase showing deformed lamella along with plagioclase-clinopyroxene-phyric granoblastic fabric within a groundmass of feldspar microphenocrysts and Fe–Ti oxides. Both normal and reverse zoning were noted in the plagioclase laths. The clinopyroxene grains contain exsolved phases such as orthopyroxene, plagioclase, magnetite, ilmenite along the cleavage traces and the orthopyroxene lamella form granules in the periphery of the clinopyroxene grains. Garnet corona also develops preferentially around plagioclase at the contact of clinopyroxene, ilmenite or magnetite. Tiny quartz and K-fs grains showed symplectic intergrowth with garnet at a few places. The product quartz formed along with garnet rims the coronal garnet and the reacting clinopyroxene. Thin amphibole corona formed along the periphery of deformed plagioclase and clinopyroxene occur as patches over the magmatic minerals. The amphibole coronas cannot be assigned to a late magmatic stage and are interpreted as reactive being restricted to the contact between clinopyroxene and plagioclase, thus postdating the crystallization of both. The amphibole and garnet do not share grain boundary in the entire rock and is thus pointing towards simultaneous crystallization. Olivine is absent. Spectacular myrmekitic growth of orthoclase and quartz rimming the plagioclase is consistent with the potash metasomatic effects that is also found in other rocks of this region. These textural features are consistent with a phase of fluid induced metamorphism (retrogression). But the appearance of coronal garnet and amphibole exclusive of each other reflects the participation if Ti as the prime reason. Presence of Ti as a reactant phase is a must for amphibole forming reactions whereas it is not so in case of garnet forming reactions although the reactants are the same plagioclase and clinopyroxene in both cases. These findings are well validated by petrographical and textural analysis. In order to obtain balanced chemical reactions that explain formation of amphibole and garnet in the mafic dyke rocks a matrix operation technique called Singular Value Decomposition (SVD) was adopted utilizing the measured chemical compositions of the minerals. The computer program C-Space was used for this purpose and the required compositional matrix. Data fed to C-Space was after doing cation-calculation of the oxide percentages obtained from EPMA analysis. The Garnet-Clinopyroxene geothermometer yielded a temperature of 650 degrees Celsius. The Garnet-Clinopyroxene-Plagioclase geobarometer and Al-in amphibole yielded roughly 7.5 kbar pressure.

Keywords: corona, dolerite, geothermometer, metasomatism, metamorphic reaction texture, retrogression

Procedia PDF Downloads 278
288 Chemical, Biochemical and Sensory Evaluation of a Quadrimix Complementary Food Developed from Sorghum, Groundnut, Crayfish and Pawpaw Blends

Authors: Ogechi Nzeagwu, Assumpta Osuagwu, Charlse Nkwoala

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Malnutrition in infants due to poverty, poor feeding practices, and high cost of commercial complementary foods among others is a concern in developing countries. The study evaluated the proximate, vitamin and mineral compositions, antinutrients and functional properties, biochemical, haematological and sensory evaluation of complementary food made from sorghum, groundnut, crayfish and paw-paw flour blends using standard procedures. The blends were formulated on protein requirement of infants (18 g/day) using Nutrisurvey linear programming software in ratio of sorghum(S), groundnut(G), crayfish(C) and pawpaw(P) flours as 50:25:10:15(SGCP1), 60:20:10:10 (SGCP2), 60:15:15:10 (SGCP3) and 60:10:20:10 (SGCP4). Plain-pap (fermented maize flour)(TCF) and cerelac (commercial complementary food) served as basal and control diets. Thirty weanling male albino rats aged 28-35 days weighing 33-60 g were purchased and used for the study. The rats after acclimatization were fed with gruel produced with the experimental diets and the control with water ad libitum daily for 35days. Effect of the blends on lipid profile, blood glucose, haematological (RBC, HB, PCV, MCV), liver and kidney function and weight gain of the rats were assessed. Acceptability of the gruel was conducted at the end of rat feeding on forty mothers of infants’ ≥ 6 months who gave their informed consent to participate using a 9 point hedonic scale. Data was analyzed for means and standard deviation, analysis of variance and means were separated using Duncan multiple range test and significance judged at 0.05, all using SPSS version 22.0. The results indicated that crude protein, fibre, ash and carbohydrate of the formulated diets were either comparable or higher than values in cerelac. The formulated diets (SGCP1- SGCP4) were significantly (P>0.05) higher in vitamin A and thiamin compared to cerelac. The iron content of the formulated diets SGCP1- SGCP4 (4.23-6.36 mg/100) were within the recommended iron intake of infants (0.55 mg/day). Phytate (1.56-2.55 mg/100g) and oxalate (0.23-0.35 mg/100g) contents of the formulated diets were within the permissible limits of 0-5%. In functional properties, bulk density, swelling index, % dispersibility and water absorption capacity significantly (P<0.05) increased and compared favourably with cerelac. The essential amino acids of the formulated blends were within the amino acid profile of the FAO/WHO/UNU reference protein for children 0.5 -2 years of age. Urea concentration of rats fed with SGCP1-SGCP4 (19.48 mmol/L),(23.76 mmol/L),(24.07 mmol/L),(23.65 mmol/L) respectively was significantly higher than that of rat fed cerelac (16.98 mmol/L); however, plain pap had the least value (9.15 mmol/L). Rats fed with SGCP1-SGCP4 (116 mg/dl), (119 mg/dl), (115 mg/dl), (117 mg/dl) respectively had significantly higher glucose levels those fed with cerelac (108 mg/dl). Liver function parameters (AST, ALP and ALT), lipid profile (triglyceride, HDL, LDL, VLDL) and hematological parameters of rats fed with formulated diets were within normal range. Rats fed SGCP1 gained more weight (90.45 g) than other rats fed with SGCP2-SGCP4 (71.65 g, 79.76 g, 75.68 g), TCF (20.13 g) and cerelac (59.06 g). In all the sensory attributes, the control was preferred with respect to the formulated diets. The formulated diets were generally adequate and may likely have potentials to meet nutrient requirements of infants as complementary food.

Keywords: biochemical, chemical evaluation, complementary food, quadrimix

Procedia PDF Downloads 170
287 Heat Transfer Phenomena Identification of a Non-Active Floor in a Stack-Ventilated Building in Summertime: Empirical Study

Authors: Miguel Chen Austin, Denis Bruneau, Alain Sempey, Laurent Mora, Alain Sommier

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An experimental study in a Plus Energy House (PEH) prototype was conducted in August 2016. It aimed to highlight the energy charge and discharge of a concrete-slab floor submitted to the day-night-cycles heat exchanges in the southwestern part of France and to identify the heat transfer phenomena that take place in both processes: charge and discharge. The main features of this PEH, significant to this study, are the following: (i) a non-active slab covering the major part of the entire floor surface of the house, which include a concrete layer 68 mm thick as upper layer; (ii) solar window shades located on the north and south facades along with a large eave facing south, (iii) large double-glazed windows covering the majority of the south facade, (iv) a natural ventilation system (NVS) composed by ten automatized openings with different dimensions: four are located on the south facade, four on the north facade and two on the shed roof (north-oriented). To highlight the energy charge and discharge processes of the non-active slab, heat flux and temperature measurement techniques were implemented, along with airspeed measurements. Ten “measurement-poles” (MP) were distributed all over the concrete-floor surface. Each MP represented a zone of measurement, where air and surface temperatures, and convection and radiation heat fluxes, were intended to be measured. The airspeed was measured only at two points over the slab surface, near the south facade. To identify the heat transfer phenomena that take part in the charge and discharge process, some relevant dimensionless parameters were used, along with statistical analysis; heat transfer phenomena were identified based on this analysis. Experimental data, after processing, had shown that two periods could be identified at a glance: charge (heat gain, positive values) and discharge (heat losses, negative values). During the charge period, on the floor surface, radiation heat exchanges were significantly higher compared with convection. On the other hand, convection heat exchanges were significantly higher than radiation, in the discharge period. Spatially, both, convection and radiation heat exchanges are higher near the natural ventilation openings and smaller far from them, as expected. Experimental correlations have been determined using a linear regression model, showing the relation between the Nusselt number with relevant parameters: Peclet, Rayleigh, and Richardson numbers. This has led to the determination of the convective heat transfer coefficient and its comparison with the convective heat coefficient resulting from measurements. Results have shown that forced and natural convection coexists during the discharge period; more accurate correlations with the Peclet number than with the Rayleigh number, have been found. This may suggest that forced convection is stronger than natural convection. Yet, airspeed levels encountered suggest that it is natural convection that should take place rather than forced convection. Despite this, Richardson number values encountered indicate otherwise. During the charge period, air-velocity levels might indicate that none air motion occurs, which might lead to heat transfer by diffusion instead of convection.

Keywords: heat flux measurement, natural ventilation, non-active concrete slab, plus energy house

Procedia PDF Downloads 416
286 Somatic Delusional Disorder Subsequent to Phantogeusia: A Case Report

Authors: Pedro Felgueiras, Ana Miguel, Nélson Almeida, Raquel Silva

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Objective: Through the study of a clinical case of delusional somatic disorder secondary to phantogeusia, we aim to highlight the importance of considering psychosomatic conditions in differential diagnosis, as well as to emphasize the complexity of its comprehension, treatment, and respective impact on patients’ functioning. Methods: Bearing this in mind, we conducted a critical analysis of a case series based on patient observations, clinical data, and complementary diagnostic methods, as well as a non-systematic review of the literature on the subject. Results: A 61-year-old female patient with no history of psychiatric conditions. Family psychiatric history of mood disorder (depression), with psychotic features found in her mother. Medical history of many comorbidities affecting different organ systems (endocrine, gastrointestinal, genitourinary, ophthalmological). Documented neuroticism traits of personality. The patient’s family described a persistent concern about several physical symptoms across her life, with a continuous effort to obtain explanations about any sensation out of her normal perception. Since being subjected to endoscopy in 2018, she started complaints of persistent phantogeusia (acid taste) and developed excessive thoughts, feelings, and behaviors associated with this somatic symptom. The patient was evaluated by several medical specialties, and an extensive panel of medical exams was carried out, excluding any disease. Besides all the investigation and with no evidence of disease signs, acute anxiety, time, and energy dispended to this symptom culminated in severe psychosocial impairment. The patient was admitted to a psychiatric ward for investigation and treatment of this clinical picture, leading to the diagnosis of the delusional somatic disorder. In order to exclude the acute organic etiology of this psychotic disorder, an analytic panel was carried out with no abnormal results. In the context of a psychotic clinical picture, a CT scan was performed, which revealed a right cortical vascular lesion. Neuropsychological evaluation was made, with the description of cognitive functioning being globally normative. During treatment with an antipsychotic (pimozide), a complete remission of the somatic delusion was associated with the disappearance of gustative perception disturbance. In follow-up, a relapse of gustative sensation was documented, and her thoughts and speech were dominated by concerns about multiple somatic symptoms. Conclusion: In terms of abnormal bodily sensations, the oral cavity is one of the frequent sites of delusional disorder. Patients with these gustatory perception distortions complain about unusual sensations without corresponding abnormal findings in the oral area. Its pathophysiology has not been fully elucidated yet. In terms of its comprehensive psychopathology, this case was hypothesized as a paranoid development of a delusional somatic disorder triggered by a post-invasive procedure phantogeusia (which is described as a possible side effect of an endoscopy) in a patient with an anankastic personality. This case presents interesting psychopathology, reinforcing the complexity of psychosomatic disorders in terms of their etiopathogenesis, clinical treatment, and long-term prognosis.

Keywords: psychosomatics, delusional somatic disorder, phantogeusia, paranoid development

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285 From Avatars to Humans: A Hybrid World Theory and Human Computer Interaction Experimentations with Virtual Reality Technologies

Authors: Juan Pablo Bertuzzi, Mauro Chiarella

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

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

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284 Governance of Climate Adaptation Through Artificial Glacier Technology: Lessons Learnt from Leh (Ladakh, India) In North-West Himalaya

Authors: Ishita Singh

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Social-dimension of Climate Change is no longer peripheral to Science, Technology and Innovation (STI). Indeed, STI is being mobilized to address small farmers’ vulnerability and adaptation to Climate Change. The experiences from the cold desert of Leh (Ladakh) in North-West Himalaya illustrate the potential of STI to address the challenges of Climate Change and the needs of small farmers through the use of Artificial Glacier Techniques. Small farmers have a unique technique of water harvesting to augment irrigation, called “Artificial Glaciers” - an intricate network of water channels and dams along the upper slope of a valley that are located closer to villages and at lower altitudes than natural glaciers. It starts to melt much earlier and supplements additional irrigation to small farmers’ improving their livelihoods. Therefore, the issue of vulnerability, adaptive capacity and adaptation strategy needs to be analyzed in a local context and the communities as well as regions where people live. Leh (Ladakh) in North-West Himalaya provides a Case Study for exploring the ways in which adaptation to Climate Change is taking place at a community scale using Artificial Glacier Technology. With the above backdrop, an attempt has been made to analyze the rural poor households' vulnerability and adaptation practices to Climate Change using this technology, thereby drawing lessons on vulnerability-livelihood interactions in the cold desert of Leh (Ladakh) in North-West Himalaya, India. The study is based on primary data and information collected from 675 households confined to 27 villages of Leh (Ladakh) in North-West Himalaya, India. It reveals that 61.18% of the population is driving livelihoods from agriculture and allied activities. With increased irrigation potential due to the use of Artificial Glaciers, food security has been assured to 77.56% of households and health vulnerability has been reduced in 31% of households. Seasonal migration as a livelihood diversification mechanism has declined in nearly two-thirds of households, thereby improving livelihood strategies. Use of tactical adaptations by small farmers in response to persistent droughts, such as selling livestock, expanding agriculture lands, and use of relief cash and foods, have declined to 20.44%, 24.74% and 63% of households. However, these measures are unsustainable on a long-term basis. The role of policymakers and societal stakeholders becomes important in this context. To address livelihood challenges, the role of technology is critical in a multidisciplinary approach involving multilateral collaboration among different stakeholders. The presence of social entrepreneurs and new actors on the adaptation scene is necessary to bring forth adaptation measures. Better linkage between Science and Technology policies, together with other policies, should be encouraged. Better health care, access to safe drinking water, better sanitary conditions, and improved standards of education and infrastructure are effective measures to enhance a community’s adaptive capacity. However, social transfers for supporting climate adaptive capacity require significant amounts of additional investment. Developing institutional mechanisms for specific adaptation interventions can be one of the most effective ways of implementing a plan to enhance adaptation and build resilience.

Keywords: climate change, adaptation, livelihood, stakeholders

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283 Environmental Impacts of Point and Non-Point Source Pollution in Krishnagiri Reservoir: A Case Study in South India

Authors: N. K. Ambujam, V. Sudha

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Reservoirs are being contaminated all around the world with point source and Non-Point Source (NPS) pollution. The most common NPS pollutants are sediments and nutrients. Krishnagiri Reservoir (KR) has been chosen for the present case study, which is located in the tropical semi-arid climatic zone of Tamil Nadu, South India. It is the main source of surface water in Krishnagiri district to meet the freshwater demands. The reservoir has lost about 40% of its water holding capacity due to sedimentation over the period of 50 years. Hence, from the research and management perspective, there is a need for a sound knowledge on the spatial and seasonal variations of KR water quality. The present study encompasses the specific objectives as (i) to investigate the longitudinal heterogeneity and seasonal variations of physicochemical parameters, nutrients and biological characteristics of KR water and (ii) to examine the extent of degradation of water quality in KR. 15 sampling points were identified by uniform stratified method and a systematic monthly sampling strategy was selected due to high dynamic nature in its hydrological characteristics. The physicochemical parameters, major ions, nutrients and Chlorophyll a (Chl a) were analysed. Trophic status of KR was classified by using Carlson's Trophic State Index (TSI). All statistical analyses were performed by using Statistical Package for Social Sciences programme, version-16.0. Spatial maps were prepared for Chl a using Arc GIS. Observations in KR pointed out that electrical conductivity and major ions are highly variable factors as it receives inflow from the catchment with different land use activities. The study of major ions in KR exhibited different trends in their values and it could be concluded that as the monsoon progresses the major ions in the water decreases or water quality stabilizes. The inflow point of KR showed comparatively higher concentration of nutrients including nitrate, soluble reactive phosphorus (SRP), total phosphors (TP), total suspended phosphorus (TSP) and total dissolved phosphorus (TDP) during monsoon seasons. This evidently showed the input of significant amount of nutrients from the catchment side through agricultural runoff. High concentration of TDP and TSP at the lacustrine zone of the reservoir during summer season evidently revealed that there was a significant release of phosphorus from the bottom sediments. Carlson’s TSI of KR ranged between 81 and 92 during northeast monsoon and summer seasons. High and permanent Cyanobacterial bloom in KR could be mainly due to the internal loading of phosphorus from the bottom sediments. According to Carlson’s TSI classification Krishnagiri reservoir was ranked in the hyper-eutrophic category. This study provides necessary basic data on the spatio-temporal variations of water quality in KR and also proves the impact of point and NPS pollution from the catchment area. High TSI warrants a greater threat for the recovery of internal P loading and hyper-eutrophic condition of KR. Several expensive internal measures for the reduction of internal loading of P were introduced by many scientists. However, the outcome of the present research suggests for the innovative algae harvesting technique for the removal of sediment nutrients.

Keywords: NPS pollution, nutrients, hyper-eutrophication, krishnagiri reservoir

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282 Plant Regeneration via Somatic Embryogenesis and Agrobacterium-Mediated Transformation in Alfalfa (Medicago sativa L.)

Authors: Sarwan Dhir, Suma Basak, Dipika Parajulee

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Alfalfa is renowned for its nutritional and biopharmaceutical value as a perennial forage legume. However, establishing a rapid plant regeneration protocol using somatic embryogenesis and efficient transformation frequency are the crucial prerequisites for gene editing in alfalfa. This study was undertaken to establish and improve the protocol for somatic embryogenesis and subsequent plant regeneration. The experiments were conducted in response to natural sensitivity using various antibiotics such as cefotaxime, carbenicillin, gentamycin, hygromycin, and kanamycin. Using 3-week-old leaf tissue, somatic embryogenesis was initiated on Gamborg’s B5 basal (B5H) medium supplemented with 3% maltose, 0.9µM Kinetin, and 4.5µM 2,4-D. Embryogenic callus (EC) obtained from the B5H medium exhibited a high rate of somatic embryo formation (97.9%) after 3 weeks when the cultures were placed in the dark. Different developmental stages of somatic embryos and cotyledonary stages were then transferred to Murashige and Skoog’s (MS) basal medium under light, resulting in a 94% regeneration rate of plantlets. Our results indicate that leaf segments can grow (tolerate) up to 450 mg/L of cefotaxime and 400 mg/L of carbenicillin in the culture medium. However, the survival threshold for hygromycin at 12.5 mg/L, kanamycin at 250 mg/L, gentamycin at 50 mg/L, and timentin (300 mg/L). The experiment to improve the protocol for achieving efficient transient gene expression in alfalfa through genetic transformation with the Agrobacterium tumefaciens pCAMBIA1304 vector was also conducted. The vector contains two reporter genes such as β-glucuronidase (GUS) and green fluorescent protein (GFP), along with a selectable hygromycin B phosphotransferase gene (HPT), all driven under the CaMV 35s promoter. Various transformation parameters were optimized using 3-week-old in vitro-grown plantlets. The different parameters such as types of explant, leaf ages, preculture days, segment sizes, wounding types, bacterial concentrations, infection periods, co-cultivation periods, different concentrations of acetosyringone, silver nitrate, and calcium chloride were optimized for transient gene expression. The transient gene expression was confirmed via histochemical GUS and GFP visualization under fluorescent microscopy. The data were analyzed based on the semi-quantitative observation of the percentage and number of blue GUS spots on different days of agro-infection. The highest percentage of GUS positivity (76.2%) was observed in 3-week-old leaf segments wounded using a scalpel blade of 11 size- after 3 days of post-incubation at a bacterial concentration of 0.6, with 2 days of preculture, 30 min of bacterial-leaf segment co-cultivation, with the addition of 150 µM acetosyringone, 4 mM calcium chloride, and 75 µM silver nitrate. Our results suggest that various factors influence T-DNA delivery in the Agrobacterium-mediated transformation of alfalfa. The stable gene expression in the putative transgenic tissue was confirmed using PCR amplification of both marker genes, indicating that gene expression in explants was not solely due to Agrobacterium, but also from transformed cells. The improved protocol could be used for generating transgenic alfalfa plants using genome editing techniques such as CRISPR/Cas9.

Keywords: Medicago sativa l. (Alfalfa), agrobacterium tumefaciens, β-glucuronidase, green fluorescent protein, transient gene

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281 Quantifying Impairments in Whiplash-Associated Disorders and Association with Patient-Reported Outcomes

Authors: Harpa Ragnarsdóttir, Magnús Kjartan Gíslason, Kristín Briem, Guðný Lilja Oddsdóttir

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Introduction: Whiplash-Associated Disorder (WAD) is a health problem characterized by motor, neurological and psychosocial symptoms, stressing the need for a multimodal treatment approach. To achieve individualized multimodal approach, prognostic factors need to be identified early using validated patient-reported and objective outcome measures. The aim of this study is to demonstrate the degree of association between patient-reported and clinical outcome measures of WAD patients in the subacute phase. Methods: Individuals (n=41) with subacute (≥1, ≤3 months) WAD (I-II), medium to high-risk symptoms, or neck pain rating ≥ 4/10 on the Visual Analog Scale (VAS) were examined. Outcome measures included measurements for movement control (Butterfly test) and cervical active range of motion (cAROM) using the NeckSmart system, a computer system using an inertial measurement unit (IMU) that connects to a computer. The IMU sensor is placed on the participant’s head, who receives visual feedback about the movement of the head. Patient-reported neck disability, pain intensity, general health, self-perceived handicap, central sensitization, and difficulties due to dizziness were measured using questionnaires. Excel and R statistical software were used for statistical analyses. Results: Forty-one participants, 15 males (37%), 26 females (63%), mean (SD) age 36.8 (±12.7), underwent data collection. Mean amplitude accuracy (AA) (SD) in the Butterfly test for easy, medium, and difficult paths were 2.4mm (0.9), 4.4mm (1.8), and 6.8mm (2.7), respectively. Mean cAROM (SD) for flexion, extension, left-, and right rotation were 46.3° (18.5), 48.8° (17.8), 58.2° (14.3), and 58.9° (15.0), respectively. Mean scores on the Neck Disability Index (NDI), VAS, Dizziness Handicap Inventory (DHI), Central Sensitization Inventory (CSI), and 36-Item Short Form Survey RAND version (RAND) were 43% (17.4), 7 (1.7), 37 (25.4), 51 (17.5), and 39.2 (17.7) respectively. Females showed significantly greater deviation for AA compared to males for easy and medium Butterfly paths (p<0.05). Statistically significant moderate to strong positive correlation was found between the DHI and easy (r=0.6, p=0.05), medium (r=0.5, p=0.05)) and difficult (r=0.5, p<0.05) Butterfly paths, between the total RAND score and all cAROMs (r between 0.4-0.7, p≤0.05) except flexion (r=0.4, p=0.7), and between the NDI score and CSI (r=0.7, p<0.01), VAS (r=0.5, p<0.01), and DHI (r=0.7, p<0.01) scores respectively. Discussion: All patient-reported and objective measures were found to be outside the reference range. Results suggest females have worse movement control in the neck in the subacute WAD phase. However, no statistical difference based on gender was found in patient-reported measures. Suggesting females might have worse movement control than males in general in this phase. The correlation found between DHI and the Butterfly test can be explained because the DHI measures proprioceptive symptoms like dizziness and eye movement disorders that can affect the outcome of movement control tests. A correlation was found between the total RAND score and cAROM, suggesting that a reduced range of motion affects the quality of life. Significance: The NeckSmart system can detect abnormalities in cAROM, fine movement control, and kinesthesia of the neck. Results suggest females have worse movement control than males. Results show a moderate to a high correlation between several patient-reported and objective measurements.

Keywords: whiplash associated disorders, car-collision, neck, trauma, subacute

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280 Transcriptomic Analysis of Acanthamoeba castellanii Virulence Alteration by Epigenetic DNA Methylation

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

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

Keywords: Acanthamoeba, DNA methylation, RNA sequencing, virulence

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279 Exploitation Pattern of Atlantic Bonito in West African Waters: Case Study of the Bonito Stock in Senegalese Waters

Authors: Ousmane Sarr

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

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

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278 Artificial Intelligence Based Method in Identifying Tumour Infiltrating Lymphocytes of Triple Negative Breast Cancer

Authors: Nurkhairul Bariyah Baharun, Afzan Adam, Reena Rahayu Md Zin

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Tumor microenvironment (TME) in breast cancer is mainly composed of cancer cells, immune cells, and stromal cells. The interaction between cancer cells and their microenvironment plays an important role in tumor development, progression, and treatment response. The TME in breast cancer includes tumor-infiltrating lymphocytes (TILs) that are implicated in killing tumor cells. TILs can be found in tumor stroma (sTILs) and within the tumor (iTILs). TILs in triple negative breast cancer (TNBC) have been demonstrated to have prognostic and potentially predictive value. The international Immune-Oncology Biomarker Working Group (TIL-WG) had developed a guideline focus on the assessment of sTILs using hematoxylin and eosin (H&E)-stained slides. According to the guideline, the pathologists use “eye balling” method on the H&E stained- slide for sTILs assessment. This method has low precision, poor interobserver reproducibility, and is time-consuming for a comprehensive evaluation, besides only counted sTILs in their assessment. The TIL-WG has therefore recommended that any algorithm for computational assessment of TILs utilizing the guidelines provided to overcome the limitations of manual assessment, thus providing highly accurate and reliable TILs detection and classification for reproducible and quantitative measurement. This study is carried out to develop a TNBC digital whole slide image (WSI) dataset from H&E-stained slides and IHC (CD4+ and CD8+) stained slides. TNBC cases were retrieved from the database of the Department of Pathology, Hospital Canselor Tuanku Muhriz (HCTM). TNBC cases diagnosed between the year 2010 and 2021 with no history of other cancer and available block tissue were included in the study (n=58). Tissue blocks were sectioned approximately 4 µm for H&E and IHC stain. The H&E staining was performed according to a well-established protocol. Indirect IHC stain was also performed on the tissue sections using protocol from Diagnostic BioSystems PolyVue™ Plus Kit, USA. The slides were stained with rabbit monoclonal, CD8 antibody (SP16) and Rabbit monoclonal, CD4 antibody (EP204). The selected and quality-checked slides were then scanned using a high-resolution whole slide scanner (Pannoramic DESK II DW- slide scanner) to digitalize the tissue image with a pixel resolution of 20x magnification. A manual TILs (sTILs and iTILs) assessment was then carried out by the appointed pathologist (2 pathologists) for manual TILs scoring from the digital WSIs following the guideline developed by TIL-WG 2014, and the result displayed as the percentage of sTILs and iTILs per mm² stromal and tumour area on the tissue. Following this, we aimed to develop an automated digital image scoring framework that incorporates key elements of manual guidelines (including both sTILs and iTILs) using manually annotated data for robust and objective quantification of TILs in TNBC. From the study, we have developed a digital dataset of TNBC H&E and IHC (CD4+ and CD8+) stained slides. We hope that an automated based scoring method can provide quantitative and interpretable TILs scoring, which correlates with the manual pathologist-derived sTILs and iTILs scoring and thus has potential prognostic implications.

Keywords: automated quantification, digital pathology, triple negative breast cancer, tumour infiltrating lymphocytes

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