Search results for: clinical advice services
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 7326

Search results for: clinical advice services

486 A 1H NMR-Linked PCR Modelling Strategy for Tracking the Fatty Acid Sources of Aldehydic Lipid Oxidation Products in Culinary Oils Exposed to Simulated Shallow-Frying Episodes

Authors: Martin Grootveld, Benita Percival, Sarah Moumtaz, Kerry L. Grootveld

Abstract:

Objectives/Hypotheses: The adverse health effect potential of dietary lipid oxidation products (LOPs) has evoked much clinical interest. Therefore, we employed a 1H NMR-linked Principal Component Regression (PCR) chemometrics modelling strategy to explore relationships between data matrices comprising (1) aldehydic LOP concentrations generated in culinary oils/fats when exposed to laboratory-simulated shallow frying practices, and (2) the prior saturated (SFA), monounsaturated (MUFA) and polyunsaturated fatty acid (PUFA) contents of such frying media (FM), together with their heating time-points at a standard frying temperature (180 oC). Methods: Corn, sunflower, extra virgin olive, rapeseed, linseed, canola, coconut and MUFA-rich algae frying oils, together with butter and lard, were heated according to laboratory-simulated shallow-frying episodes at 180 oC, and FM samples were collected at time-points of 0, 5, 10, 20, 30, 60, and 90 min. (n = 6 replicates per sample). Aldehydes were determined by 1H NMR analysis (Bruker AV 400 MHz spectrometer). The first (dependent output variable) PCR data matrix comprised aldehyde concentration scores vectors (PC1* and PC2*), whilst the second (predictor) one incorporated those from the fatty acid content/heating time variables (PC1-PC4) and their first-order interactions. Results: Structurally complex trans,trans- and cis,trans-alka-2,4-dienals, 4,5-epxy-trans-2-alkenals and 4-hydroxy-/4-hydroperoxy-trans-2-alkenals (group I aldehydes predominantly arising from PUFA peroxidation) strongly and positively loaded on PC1*, whereas n-alkanals and trans-2-alkenals (group II aldehydes derived from both MUFA and PUFA hydroperoxides) strongly and positively loaded on PC2*. PCR analysis of these scores vectors (SVs) demonstrated that PCs 1 (positively-loaded linoleoylglycerols and [linoleoylglycerol]:[SFA] content ratio), 2 (positively-loaded oleoylglycerols and negatively-loaded SFAs), 3 (positively-loaded linolenoylglycerols and [PUFA]:[SFA] content ratios), and 4 (exclusively orthogonal sampling time-points) all powerfully contributed to aldehydic PC1* SVs (p 10-3 to < 10-9), as did all PC1-3 x PC4 interaction ones (p 10-5 to < 10-9). PC2* was also markedly dependent on all the above PC SVs (PC2 > PC1 and PC3), and the interactions of PC1 and PC2 with PC4 (p < 10-9 in each case), but not the PC3 x PC4 contribution. Conclusions: NMR-linked PCR analysis is a valuable strategy for (1) modelling the generation of aldehydic LOPs in heated cooking oils and other FM, and (2) tracking their unsaturated fatty acid (UFA) triacylglycerol sources therein.

Keywords: frying oils, lipid oxidation products, frying episodes, chemometrics, principal component regression, NMR Analysis, cytotoxic/genotoxic aldehydes

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485 Feasibility and Acceptability of Modified Mindfulness-Based Stress Reduction for Health Care Workers in Acute Stress during the COVID-19 Pandemic

Authors: Susan Evans, Janna Gordon-Elliott, Katarzyna Wyka, Virginia Mutch

Abstract:

During the rise of the COVID-19 pandemic, healthcare workers needed an intervention that could address their profound acute stress. Mindfulness-based stress reduction (MBSR) is a program that has long established effectiveness for mental and physical health outcomes. In recent years, MBSR has been modified such that the duration of both class time and number of sessions has been abbreviated, and its delivery has been adapted for online dissemination, thus increasing the likelihood that individuals who could most benefit from the program would do so. We sought to investigate whether a brief, online version of MBSR could be feasible and acceptable for health care workers (HCW) in acute stress in response to the COVID-19 pandemic. Participants were recruited via an email sent to all hospital employees, which spans residents, physicians, nurses, housekeeping, lab technicians, administrators, and others. Participating HCW were asked about their previous experience with mindfulness and asked to commit to a minimum of 3 sessions. They were then provided with four weekly 1-hour sessions online that included the major mindfulness exercises taught during traditional MBSR programs (i.e., body scan, sitting meditation, mindful eating, and yoga). Participants were provided with supporting slides, videos, demonstrations and asked to track their practice. Hospital staff enrolled in the program; by the end of the first day of recruitment, 40 had applied; by the start date, about 100 were enrolled, and n attended a minimum of 3 sessions, supporting feasibility. Hospital staff also participated and practiced the mindfulness exercises (n=42), thus supporting acceptability. Participants reported that the program was logical, successful, and worth recommending both before starting the program and after completing it (M= 22.02 and M=21.76, respectively, possible range 0-27). There was a slight decline in the belief in improvement in health and well-being due to the program (ES=.37, p=.021). Secondary hypotheses regarding participants’ self-reported stress and levels of mindfulness were also supported, such that participants reported improvements in perceived stress (ES=.45, p=.006), compassion satisfaction, burnout, and secondary traumatic stress (ES=.41, ES=.31, ES=.35, respectively, p<.05). Participants reported significant improvements in the describing facet of mindfulness (ES=.49, p=.004), while all other facets (observing, acting with awareness, nonjudging of inner experience, nonreactivity to inner experience) remained unchanged pre- to post-program. Results from this study suggest that an abridged, online version of MBSR is feasible and accessible to health care workers in acute stress and provides benefits expected from traditional MBSR programs. The lack of a randomized control group limits generalizability. We intend to provide a structure, framework, and lessons learned to hospital administrators and clinical staff seeking to support their employees in acute stress.

Keywords: acute stress, health care workers, mindfulness, online interventions

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

Authors: Antonio Ruiz Gonzalez, Kwang-Leong Choy

Abstract:

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

Keywords: hyperkalemia, drift, AACVD, organosilicon

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483 Optimization of Rehabilitation in Scapolohumeral Periarthrosis Using Botulinum Toxin

Authors: M. A. Akulov, V. O. Zaharov, A. A. Tomskij

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Introduction: Scapulohumeral periarthrosis, resulting as a reaction to mechanical injury of shoulder tendons and muscles, is associated with high incidence of temporal and permanent disability. There is a strong need for investigation of treatment of that patient group. Severe pain leads to limitation of movements range, which result in secondary alterations of joint capsule and ligamentous apparatus. Muscle tension and edema, swelling of fascial and fibrous structures result in nerve and vascular compression in intramuscular and osseo-muscular-fibrous spaces. Botulinum toxin injection leads to decrease of muscle tone, increase of movements range and associated pain alleviation. Study aim: Optimization of rehabilitation process in scapolohumeral periarthrosis using Xeomin. Patients and methods: 40 patients aged 37-56 years with scapulohumeral periarthrosis were evaluated. Patients were divided into two groups according to treatment regimen. The first (main) group included 21 patients, receiving intramuscular Xeomin 150-200 U in the area of brachio-scapular joint and trigger points (inducing motion range limitation and pain). Treatment procedures were combined with physical therapy and osteopathic procedures. The second (control) group included 19 patients, receiving conventional physical therapy and osteopathic procedures. The evaluation and efficacy comparison was carried out using McGill pain questionnaire, Clinical Global Impression scale (CGI), and patient-reported increase of brachio-scapular joint movement range and pain decrease at 1, 3 and 6 months of treatment. Results. The study demonstrated a significant improvement in the main group after one month of treatment, which persisted during months of treatment. At baseline, rank pain index on McGill pain questionnaire was 18,4±4,9 and 17,8±5,1 in the main and control group, respectively (p > 0,05). At 1 month of treatment we observed a significant decrease of pain syndrome (no pain or modest pain) and increase of movement range in angular degrees in the main group (р < 0,05). In the control group significant improvements were observed only on the 3 month of treatment (р < 0,05), but at 6 months of treatment the improvement in pain syndrome and motion range in brachio-scapular joint was significantly smaller, than in the main group. Rank pain index on McGill pain scale was 5,2±1,8 in the main group compared to 12,0±2,6 in the control group (р < 0,05). At 6 months of treatment patients in the first group reported a significant/highly significant improvement of general health on CGI, whereas in the second group most patients reported a minimal improvement. We observed a sustained and persistent improvement of motion range in brachio-scapular joint in the main group. Conclusion: Xeomin injections as a part of rehabilitation process in scapulohumeral periarthrosis lead to reduced time and increased quality of rehabilitation.

Keywords: botulinum toxin, rehabilitation, scapulohumeral periarthrosis

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482 Growth and Differentiation of Mesenchymal Stem Cells on Titanium Alloy Ti6Al4V and Novel Beta Titanium Alloy Ti36Nb6Ta

Authors: Eva Filová, Jana Daňková, Věra Sovková, Matej Daniel

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Titanium alloys are biocompatible metals that are widely used in clinical practice as load bearing implants. The chemical modification may influence cell adhesion, proliferation, and differentiation as well as stiffness of the material. The aim of the study was to evaluate the adhesion, growth and differentiation of pig mesenchymal stem cells on the novel beta titanium alloy Ti36Nb6Ta compared to standard medical titanium alloy Ti6Al4V. Discs of Ti36Nb6Ta and Ti6Al4V alloy were sterilized by ethanol, put in 48-well plates, and seeded by pig mesenchymal stem cells at the density of 60×103/cm2 and cultured in Minimum essential medium (Sigma) supplemented with 10% fetal bovine serum and penicillin/streptomycin. Cell viability was evaluated using MTS assay (CellTiter 96® AQueous One Solution Cell Proliferation Assay;Promega), cell proliferation using Quant-iT™ ds DNA Assay Kit (Life Technologies). Cells were stained immunohistochemically using monoclonal antibody beta-actin, and secondary antibody conjugated with AlexaFluor®488 and subsequently the spread area of cells was measured. Cell differentiation was evaluated by alkaline phosphatase assay using p-nitrophenyl phosphate (pNPP) as a substrate; the reaction was stopped by NaOH, and the absorbance was measured at 405 nm. Osteocalcin, specific bone marker was stained immunohistochemically and subsequently visualized using confocal microscopy; the fluorescence intensity was analyzed and quantified. Moreover, gene expression of osteogenic markers osteocalcin and type I collagen was evaluated by real-time reverse transcription-PCR (qRT-PCR). For statistical evaluation, One-way ANOVA followed by Student-Newman-Keuls Method was used. For qRT-PCR, the nonparametric Kruskal-Wallis Test and Dunn's Multiple Comparison Test were used. The absorbance in MTS assay was significantly higher on titanium alloy Ti6Al4V compared to beta titanium alloy Ti36Nb6Ta on days 7 and 14. Mesenchymal stem cells were well spread on both alloys, but no difference in spread area was found. No differences in alkaline phosphatase assay, fluorescence intensity of osteocalcin as well as the expression of type I collagen, and osteocalcin genes were observed. Higher expression of type I collagen compared to osteocalcin was observed for cells on both alloys. Both beta titanium alloy Ti36Nb6Ta and titanium alloy Ti6Al4V Ti36Nb6Ta supported mesenchymal stem cellsˈ adhesion, proliferation and osteogenic differentiation. Novel beta titanium alloys Ti36Nb6Ta is a promising material for bone implantation. The project was supported by the Czech Science Foundation: grant No. 16-14758S, the Grant Agency of the Charles University, grant No. 1246314 and by the Ministry of Education, Youth and Sports NPU I: LO1309.

Keywords: beta titanium, cell growth, mesenchymal stem cells, titanium alloy, implant

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481 Gender Differences in Morbid Obese Children: Clinical Significance of Two Diagnostic Obesity Notation Model Assessment Indices

Authors: Mustafa M. Donma, Orkide Donma, Murat Aydin, Muhammet Demirkol, Burcin Nalbantoglu, Aysin Nalbantoglu, Birol Topcu

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Childhood obesity is an ever increasing global health problem, affecting both developed and developing countries. Accurate evaluation of obesity in children requires difficult and detailed investigation. In our study, obesity in children was evaluated using new body fat ratios and indices. Assessment of anthropometric measurements, as well as some ratios, is important because of the evaluation of gender differences particularly during the late periods of obesity. A total of 239 children; 168 morbid obese (MO) (81 girls and 87 boys) and 71 normal weight (NW) (40 girls and 31 boys) children, participated in the study. Informed consent forms signed by the parents were obtained. Ethics Committee approved the study protocol. Mean ages (years)±SD calculated for MO group were 10.8±2.9 years in girls and 10.1±2.4 years in boys. The corresponding values for NW group were 9.0±2.0 years in girls and 9.2±2.1 years in boys. Mean body mass index (BMI)±SD values for MO group were 29.1±5.4 kg/m2 and 27.2±3.9 kg/m2 in girls and boys, respectively. These values for NW group were calculated as 15.5±1.0 kg/m2 in girls and 15.9±1.1 kg/m2 in boys. Groups were constituted based upon BMI percentiles for age-and-sex values recommended by WHO. Children with percentiles >99 were grouped as MO and children with percentiles between 85 and 15 were considered NW. The anthropometric measurements were recorded and evaluated along with the new ratios such as trunk-to-appendicular fat ratio, as well as indices such as Index-I and Index-II. The body fat percent values were obtained by bio-electrical impedance analysis. Data were entered into a database for analysis using SPSS/PASW 18 Statistics for Windows statistical software. Increased waist-to-hip circumference (C) ratios, decreased head-to-neck C, height ‘to’ ‘two’-‘to’-waist C and height ‘to’ ‘two’-‘to’-hip C ratios were observed in parallel with the development of obesity (p≤0.001). Reference value for height ‘to’ ‘two’-‘to’-hip ratio was detected as approximately 1.0. Index-II, based upon total body fat mass, showed much more significant differences between the groups than Index-I based upon weight. There was not any difference between trunk-to-appendicular fat ratios of NW girls and NW boys (p≥0.05). However, significantly increased values for MO girls in comparison with MO boys were observed (p≤0.05). This parameter showed no difference between NW and MO states in boys (p≥0.05). However, statistically significant increase was noted in MO girls compared to their NW states (p≤0.001). Trunk-to-appendicular fat ratio was the only fat-based parameter, which showed gender difference between NW and MO groups. This study has revealed that body ratios and formula based upon body fat tissue are more valuable parameters than those based on weight and height values for the evaluation of morbid obesity in children.

Keywords: anthropometry, childhood obesity, gender, morbid obesity

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480 Study on Health Status and Health Promotion Models for Prevention of Cardiovascular Disease in Asylum Seekers at Asylum Seekers Center, Kupang-Indonesia

Authors: Era Dorihi Kale, Sabina Gero, Uly Agustine

Abstract:

Asylum seekers are people who come to other countries to get asylum. In line with that, they also carry the culture and health behavior of their country, which is very different from the new country they currently live in. This situation raises problems, also in the health sector. The approach taken must also be a culturally sensitive approach, where the culture and habits of the refugee's home area are also valued so that the health services provided can be right on target. Some risk factors that already exist in this group are lack of activity, consumption of fast food, smoking, and stress levels that are quite high. Overall this condition will increase the risk of an increased incidence of cardiovascular disease. This research is a descriptive and experimental study. The purpose of this study is to identify health status and develop a culturally sensitive health promotion model, especially related to the risk of cardiovascular disease for asylum seekers in detention homes in the city of Kupang. This research was carried out in 3 stages, stage 1 was conducting a survey of health problems and the risk of asylum seeker cardiovascular disease, Stage 2 developed a health promotion model, and stage 3 conducted a testing model of health promotion carried out. There were 81 respondents involved in this study. The variables measured were: health status, risk of cardiovascular disease and, health promotion models. Method of data collection: Instruments (questionnaires) were distributed to respondents answered for anamnese health status; then, cardiovascular risk measurements were taken. After that, the preparation of information needs and the compilation of booklets on the prevention of cardiovascular disease is carried out. The compiled booklet was then translated into Farsi. After that, the booklet was tested. Respondent characteristics: average lived in Indonesia for 4.38 years, the majority were male (90.1%), and most were aged 15-34 years (90.1%). There are several diseases that are often suffered by asylum seekers, namely: gastritis, headaches, diarrhea, acute respiratory infections, skin allergies, sore throat, cough, and depression. The level of risk for asylum seekers experiencing cardiovascular problems is 4 high risk people, 6 moderate risk people, and 71 low risk people. This condition needs special attention because the number of people at risk is quite high when compared to the age group of refugees. This is very related to the level of stress experienced by the refugees. The health promotion model that can be used is the transactional stress and coping model, using Persian (oral) and English for written information. It is recommended for health practitioners who care for refugees to always pay attention to aspects of culture (especially language) as well as the psychological condition of asylum seekers to make it easier to conduct health care and promotion. As well for further research, it is recommended to conduct research, especially relating to the effect of psychological stress on the risk of cardiovascular disease in asylum seekers.

Keywords: asylum seekers, health status, cardiovascular disease, health promotion

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479 [Keynote] Implementation of Quality Control Procedures in Radiotherapy CT Simulator

Authors: B. Petrović, L. Rutonjski, M. Baucal, M. Teodorović, O. Čudić, B. Basarić

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Purpose/Objective: Radiotherapy treatment planning requires use of CT simulator, in order to acquire CT images. The overall performance of CT simulator determines the quality of radiotherapy treatment plan, and at the end, the outcome of treatment for every single patient. Therefore, it is strongly advised by international recommendations, to set up a quality control procedures for every machine involved in radiotherapy treatment planning process, including the CT scanner/ simulator. The overall process requires number of tests, which are used on daily, weekly, monthly or yearly basis, depending on the feature tested. Materials/Methods: Two phantoms were used: a dedicated phantom CIRS 062QA, and a QA phantom obtained with the CT simulator. The examined CT simulator was Siemens Somatom Definition as Open, dedicated for radiation therapy treatment planning. The CT simulator has a built in software, which enables fast and simple evaluation of CT QA parameters, using the phantom provided with the CT simulator. On the other hand, recommendations contain additional test, which were done with the CIRS phantom. Also, legislation on ionizing radiation protection requires CT testing in defined periods of time. Taking into account the requirements of law, built in tests of a CT simulator, and international recommendations, the intitutional QC programme for CT imulator is defined, and implemented. Results: The CT simulator parameters evaluated through the study were following: CT number accuracy, field uniformity, complete CT to ED conversion curve, spatial and contrast resolution, image noise, slice thickness, and patient table stability.The following limits are established and implemented: CT number accuracy limits are +/- 5 HU of the value at the comissioning. Field uniformity: +/- 10 HU in selected ROIs. Complete CT to ED curve for each tube voltage must comply with the curve obtained at comissioning, with deviations of not more than 5%. Spatial and contrast resultion tests must comply with the tests obtained at comissioning, otherwise machine requires service. Result of image noise test must fall within the limit of 20% difference of the base value. Slice thickness must meet manufacturer specifications, and patient stability with longitudinal transfer of loaded table must not differ of more than 2mm vertical deviation. Conclusion: The implemented QA tests gave overall basic understanding of CT simulator functionality and its clinical effectiveness in radiation treatment planning. The legal requirement to the clinic is to set up it’s own QA programme, with minimum testing, but it remains user’s decision whether additional testing, as recommended by international organizations, will be implemented, so to improve the overall quality of radiation treatment planning procedure, as the CT image quality used for radiation treatment planning, influences the delineation of a tumor and calculation accuracy of treatment planning system, and finally delivery of radiation treatment to a patient.

Keywords: CT simulator, radiotherapy, quality control, QA programme

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478 Advancing Food System Resilience by Pseudocereals Utilization

Authors: Yevheniia Varyvoda, Douglas Taren

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At the aggregate level, climate variability, the rising number of active violent conflicts, globalization and industrialization of agriculture, the loss in diversity of crop species, the increase in demand for agricultural production, and the adoption of healthy and sustainable dietary patterns are exacerbating factors of food system destabilization. The importance of pseudocereals to fuel and sustain resilient food systems is recognized by leading organizations working to end hunger, particularly for their critical capability to diversify livelihood portfolios and provide plant-sourced healthy nutrition in the face of systemic shocks and stresses. Amaranth, buckwheat, and quinoa are the most promising and used pseudocereals for ensuring food system resilience in the reality of climate change due to their high nutritional profile, good digestibility, palatability, medicinal value, abiotic stress tolerance, pest and disease resistance, rapid growth rate, adaptability to marginal and degraded lands, high genetic variability, low input requirements, and income generation capacity. The study provides the rationale and examples of advancing local and regional food systems' resilience by scaling up the utilization of amaranth, buckwheat, and quinoa along all components of food systems to architect indirect nutrition interventions and climate-smart approaches. Thus, this study aims to explore the drivers for ancient pseudocereal utilization, the potential resilience benefits that can be derived from using them, and the challenges and opportunities for pseudocereal utilization within the food system components. The PSALSAR framework regarding the method for conducting systematic review and meta-analysis for environmental science research was used to answer these research questions. Nevertheless, the utilization of pseudocereals has been slow for a number of reasons, namely the increased production of commercial and major staples such as maize, rice, wheat, soybean, and potato, the displacement due to pressure from imported crops, lack of knowledge about value-adding practices in food supply chain, limited technical knowledge and awareness about nutritional and health benefits, absence of marketing channels and limited access to extension services and information about resilient crops. The success of climate-resilient pathways based on pseudocereal utilization underlines the importance of co-designed activities that use modern technologies, high-value traditional knowledge of underutilized crops, and a strong acknowledgment of cultural norms to increase community-level economic and food system resilience.

Keywords: resilience, pseudocereals, food system, climate change

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477 Use of PACER Application as Physical Activity Assessment Tool: Results of a Reliability and Validity Study

Authors: Carine Platat, Fatima Qshadi, Ghofran Kayed, Nour Hussein, Amjad Jarrar, Habiba Ali

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Nowadays, smartphones are very popular. They are offering a variety of easy-to-use and free applications among which step counters and fitness tests. The number of users is huge making of such applications a potentially efficient new strategy to encourage people to become more active. Nonetheless, data on their reliability and validity are very scarce and when available, they are often negative and contradictory. Besides, weight status, which is likely to introduce a bias in the physical activity assessment, was not often considered. Hence, the use of these applications as motivational tool, assessment tool and in research is questionable. PACER is one of the free step counters application. Even though it is one of the best rated free application by users, it has never been tested for reliability and validity. Prior any use of PACER, this remains to be investigated. The objective of this work is to investigate the reliability and validity of the smartphone application PACER in measuring the number of steps and in assessing the cardiorespiratory fitness by the 6 minutes walking test. 20 overweight or obese students (10 male and 10 female) were recruited at the United Arab Emirate University, aged between 18 and 25 years old. Reliability and validity were tested in real life conditions and in controlled conditions by using a treadmill. Test-retest experiments were done with PACER on 2 days separated by a week in real life conditions (24 hours each time) and in controlled conditions (30 minutes on treadmill, 3km/h). Validity was tested against the pedometer OMRON in the same conditions. During treadmill test, video was recorded and steps numbers were compared between PACER, pedometer and video. The validity of PACER in estimating the cardiorespiratory fitness (VO2max) as part of the 6 minutes walking test (6MWT) was studied against the 20m shuttle running test. Reliability was studied by calculating intraclass correlation coefficients (ICC), 95% confidence interval (95%CI) and by Bland-Altman plots. Validity was studied by calculating Spearman correlation coefficient (rho) and Bland-Altman plots. PACER reliability was good in both male and female in real life conditions (p≤10-3) but only in female in controlled conditions (p=0.01). PACER was valid against OMRON pedometer in male and female in real life conditions (rho=0.94, p≤10-3 ; rho=0.64, p=0.01, in male and female respectively). In controlled conditions, PACER was not valid against pedometer. But, PACER was valid against video in female (rho=0.72, p≤10-3). PACER was valid against the shuttle run test in male and female (rho-=0.66, p=0.01 ; rho=0.51, p=0.04) to estimate VO2max. This study provides data on the reliability and viability of PACER in overweight or obese male and female young adults. Globally, PACER was shown as reliable and valid in real life conditions in overweight or obese male and female to count steps and assess fitness. This supports the use of PACER to assess and promote physical activity in clinical follow-up and community interventions.

Keywords: smartphone application, pacer, reliability, validity, steps, fitness, physical activity

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476 Study of Silent Myocardial Ischemia in Type 2 Diabeic Males: Egyptian Experience

Authors: Ali Kassem, Yhea Kishik, Ali Hassan, Mohamed Abdelwahab

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Introduction: Accelerated coronary and peripheral vascular atherosclerosis is one of the most common and chronic complications of diabetes mellitus. A recent aspect of coronary artery disease in this condition is its silent nature. The aim of the work: Detection of the prevalence of silent myocardial ischemia (SMI) in Upper Egypt type 2 diabetic males and to select male diabetic population who should be screened for SMI. Patients and methods: 100 type 2 diabetic male patients with a negative history of angina or anginal equivalent symptoms and 30 healthy control were included. Full medical history and thorough clinical examination were done for all participants. Fasting and post prandial blood glucose level, lipid profile, (HbA1c), microalbuminuria, and C-reactive protein were done for all participants Resting ECG, trans-thoracic echocardiography, treadmill exercise ECG, myocardial perfusion imaging were done for all participants and patients positive for one or more NITs were subjected for coronary angiography. Results Twenty nine patients (29%) were positive for one or more NITs in the patients group compared to only one case (3.3%) in the controls. After coronary angiography, 20 patients were positive for significant coronary artery stenosis in the patients group, while it was refused to be done by the patient in the controls. There were statistical significant difference between the two groups regarding, hypertension, dyslipidemia and obesity, family history of DM and IHD with higher levels of microalbuminuria, C-reactive protein, total lipids in patient group versus controls According to coronary angiography, patients were subdivided into two subgroups, 20 positive for SMI (positive for coronary angiography) and 80 negative for SMI (negative for coronary angiography). No statistical difference regarding family history of DM and type of diabetic therapy was found between the two subgroups. Yet, smoking, hypertension, obesity, dyslipidemia and family history of IHD were significantly higher in diabetics positive versus those negative for SMI. 90% of patients in subgroup positive for SMI had two or more cardiac risk factors while only two patients had one cardiac risk factor (10%). Uncontrolled DM was detected more in patients positive for SMI. Diabetic complications were more prevalent in patients positive for SMI versus those negative for SMI. Most of the patients positive for SMI have DM more than 5 years duration. Resting ECG and resting Echo detected only 6 and 11 cases, respectively, of the 20 positive cases in group positive for SMI compared to treadmill exercise ECG and myocardial perfusion imaging that detected 16 and 18 cases respectively, Conclusion: Type 2 diabetic male patients should be screened for detection of SMI when aged above 50 years old, diabetes duration is more than 5 years, presence of two or more cardiac risk factors and/or patients suffering from one or more of the chronic diabetic complications. CRP, is an important parameter for selection of type 2 diabetic male patients who should be screened for SMI. Non invasive cardiac tests are reliable for screening of SMI in these patients in our locality.

Keywords: C-reactive protein, Silent myocardial ischemia, Stress tests, type 2 DM

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475 A Clinical Audit on Screening Women with Subfertility Using Transvaginal Scan and Hysterosalpingo Contrast Sonography

Authors: Aarti M. Shetty, Estela Davoodi, Subrata Gangooly, Anita Rao-Coppisetty

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Background: Testing Patency of Fallopian Tubes is among one of the several protocols for investigating Subfertile Couples. Both, Hysterosalpingogram (HSG) and Laparoscopy and dye test have been used as Tubal patency test for several years, with well-known limitation. Hysterosalpingo Contrast Sonography (HyCoSy) can be used as an alternative tool to HSG, to screen patency of Fallopian tubes, with an advantage of being non-ionising, and also, use of transvaginal scan to diagnose pelvic pathology. Aim: To determine the indication and analyse the performance of transvaginal scan and HyCoSy in Broomfield Hospital. Methods: We retrospectively analysed fertility workup of 282 women, who attended HyCoSy clinic at our institution from January 2015 to June 2016. An Audit proforma was designed, to aid data collection. Data was collected from patient notes and electronic records, which included patient demographics; age, parity, type of subfertility (primary or secondary), duration of subfertility, past medical history and base line investigation (hormone profile and semen analysis). Findings of the transvaginal scan, HyCoSy and Laparoscopy were also noted. Results: The most common indication for referral were as a part of primary fertility workup on couples who had failure to conceive despite intercourse for a year, other indication for referral were recurrent miscarriage, history of ectopic pregnancy, post reversal of sterilization(vasectomy and tuboplasty), Post Gynaecology surgery(Loop excision, cone biopsy) and amenorrhea. Basic Fertility workup showed 34% men had abnormal semen analysis. HyCoSy was successfully completed in 270 (95%) women using ExEm foam and Transvaginal Scan. Of the 270 patients, 535 tubes were examined in total. 495/535 (93%) tubes were reported as patent, 40/535 (7.5%) tubes were reported as blocked. A total of 17 (6.3%) patients required laparoscopy and dye test after HyCoSy. In these 17 patients, 32 tubes were examined under laparoscopy, and 21 tubes had findings similar to HyCoSy, with a concordance rate of 65%. In addition to this, 41 patients had some form of pelvic pathology (endometrial polyp, fibroid, cervical polyp, fibroid, bicornuate uterus) detected during transvaginal scan, who referred to corrective surgeries after attending HyCoSy Clinic. Conclusion: Our audit shows that HyCoSy and Transvaginal scan can be a reliable screening test for low risk women. Furthermore, it has competitive diagnostic accuracy to HSG in identifying tubal patency, with an additional advantage of screening for pelvic pathology. With addition of 3D Scan, pulse Doppler and other non-invasive imaging modality, HyCoSy may potentially replace Laparoscopy and chromopertubation in near future.

Keywords: hysterosalpingo contrast sonography (HyCoSy), transvaginal scan, tubal infertility, tubal patency test

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474 Screening Tools and Its Accuracy for Common Soccer Injuries: A Systematic Review

Authors: R. Christopher, C. Brandt, N. Damons

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Background: The sequence of prevention model states that by constant assessment of injury, injury mechanisms and risk factors are identified, highlighting that collecting and recording of data is a core approach for preventing injuries. Several screening tools are available for use in the clinical setting. These screening techniques only recently received research attention, hence there is a dearth of inconsistent and controversial data regarding their applicability, validity, and reliability. Several systematic reviews related to common soccer injuries have been conducted; however, none of them addressed the screening tools for common soccer injuries. Objectives: The purpose of this study was to conduct a review of screening tools and their accuracy for common injuries in soccer. Methods: A systematic scoping review was performed based on the Joanna Briggs Institute procedure for conducting systematic reviews. Databases such as SPORT Discus, Cinahl, Medline, Science Direct, PubMed, and grey literature were used to access suitable studies. Some of the key search terms included: injury screening, screening, screening tool accuracy, injury prevalence, injury prediction, accuracy, validity, specificity, reliability, sensitivity. All types of English studies dating back to the year 2000 were included. Two blind independent reviewers selected and appraised articles on a 9-point scale for inclusion as well as for the risk of bias with the ACROBAT-NRSI tool. Data were extracted and summarized in tables. Plot data analysis was done, and sensitivity and specificity were analyzed with their respective 95% confidence intervals. I² statistic was used to determine the proportion of variation across studies. Results: The initial search yielded 95 studies, of which 21 were duplicates, and 54 excluded. A total of 10 observational studies were included for the analysis: 3 studies were analysed quantitatively while the remaining 7 were analysed qualitatively. Seven studies were graded low and three studies high risk of bias. Only high methodological studies (score > 9) were included for analysis. The pooled studies investigated tools such as the Functional Movement Screening (FMS™), the Landing Error Scoring System (LESS), the Tuck Jump Assessment, the Soccer Injury Movement Screening (SIMS), and the conventional hamstrings to quadriceps ratio. The accuracy of screening tools was of high reliability, sensitivity and specificity (calculated as ICC 0.68, 95% CI: 52-0.84; and 0.64, 95% CI: 0.61-0.66 respectively; I² = 13.2%, P=0.316). Conclusion: Based on the pooled results from the included studies, the FMS™ has a good inter-rater and intra-rater reliability. FMS™ is a screening tool capable of screening for common soccer injuries, and individual FMS™ scores are a better determinant of performance in comparison with the overall FMS™ score. Although meta-analysis could not be done for all the included screening tools, qualitative analysis also indicated good sensitivity and specificity of the individual tools. Higher levels of evidence are, however, needed for implication in evidence-based practice.

Keywords: accuracy, screening tools, sensitivity, soccer injuries, specificity

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473 The Invisibility of Production: A Comparative Study of the Marker of Modern Urban-Centric Economic Development

Authors: Arpita Banerjee

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We now live in a world where half of the human population is city dwellers. The migration of people from rural to urban areas is rising continuously. But, the promise of a greater wage and better quality of life cannot keep up with the pace of migration. The rate of urbanization is much higher in developing countries. The UN predicts that 95 percent of this urban expansion will take place in the developing world in the next few decades. The population in the urban settlements of the developing nations is soaring, and megacities like Mumbai, Dhaka, Jakarta, Karachi, Manila, Shanghai, Rio de Janeiro, Lima, and Kinshasa are crammed with people, a majority of whom are migrants. Rural-urban migration has taken a new shape with the rising number of smaller cities. Apart from the increase in non-agricultural economic activities, growing demand for resources and energy, an increase in wastes and pollution, and a greater ecological footprint, there is another significant characteristic of the current wave of urbanization. This paper analyses that important marker of urbanization. It is the invisibility of production sites. The growing urban space ensures that the producers, the production sites, or the process stay beyond urban visibility. In cities and towns, living is majorly about earning money in either the informal service and small scale manufacturing sectors (a major part of which is food preparation), or the formal service sector. In the cases of both the informal service and small scale manufacturing or the formal service sector, commodity creation cannot be seen. The urban space happens to be the marketplace, where nature and its services, along with the non-urban labour, cannot be seen unless it is sold in the market. Hence, the consumers are now increasingly becoming disengaged from the producers. This paper compares the rate of increase in the size of and employment in the informal sector and/or that of the formal sector of some selected urban areas of India. Also, a comparison over the years of the aforementioned characteristics is presented in this paper, in order to find out how the anonymity of the producers to the urban consumers have grown as urbanization has risen. This paper also analyses the change in the transport cost of goods into the cities and towns of India and supports that claim made here that the invisibility of production is a crucial marker of modern-day urban-centric economic development. Such urbanization has an important ecological impact. The invisibility of the production site saves the urban consumer society from dealing with the ethical and ecological aspects of the production process. Once the real sector production is driven out of the cities and towns, the invisible ethical and ecological impacts of the growing urban consumption frees the consumers from associating themselves with any responsibility towards those impacts.

Keywords: ecological impact of urbanization, informal sector, invisibility of production, urbanization

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472 “Uninformed” Religious Orientation Can Lead to Violence in Any Given Community: The Case of African Independence Churches in South Africa

Authors: Ngwako Daniel Sebola

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Introductory Statement: Religions are necessary as they offer and teach something to their adherence. People in one religion may not have a complete understanding of the Supreme Being (Deity) in a certain religion other than their own. South Africa, like other countries in the world, consists of various religions, including Christianity. Almost 80% of South African population adheres to the Christian faith, though in different denominations and sects. Each church fulfils spiritual needs that perhaps others cannot fill. African Independent Churches is one of the denominations in the country. These churches arose as a protest to the Western forms and expressions of Christianity. Their major concern was to develop an indigenous expression of Christianity. The relevance of African Independent Churches includes addressing the needs of the people holistically. Controlling diseases was an important aspect of change in different historical periods. Through healing services, leaders of African churches are able to attract many followers. The healing power associated with the founders of many African Initiated Churches leads to people following and respecting them as true leaders within many African communities. Despite its strong points, African Independent Churches, like many others, face a variety of challenges, especially conflicts. Ironically, destructive conflicts resulted in violence.. Such violence demonstrates a lack of informed religious orientation among those concerned. This paper investigates and analyses the causes of conflict and violence in the African Independent Church. The researcher used the Shembe and International Pentecostal Holiness Churches, in South Africa, as a point of departure. As a solution to curb violence, the researcher suggests useful strategies in handling conflicts. Methodology: Comparative and qualitative approaches have been used as methods of collecting data in this research. The intention is to analyse the similarities and differences of violence among members of the Shembe and International Pentecostal Holiness Churches. Equally important, the researcher aims to obtain data through interviews, questionnaires, focus groups, among others. The researcher aims to interview fifteen individuals from both churches. Finding: Leadership squabbles and power struggle appear to be the main contributing factors of violence in many Independent Churches. Ironically, violence resulted in the loss of life and destruction of properties, like in the case of the Shembe and International Pentecostal Holiness Churches. Violence is an indication that congregations and some leaders have not been properly equipped to deal with conflict. Concluding Statement: Conflict is a common part of every human existence in any given community. The concern is when such conflict becomes contagious; it leads to violence. There is a need to understand consciously and objectively towards devising the appropriate measures to handle the conflict. Conflict management calls for emotional maturity, self-control, empathy, patience, tolerance and informed religious orientation.

Keywords: African, church, religion, violence

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471 Functional Analysis of Variants Implicated in Hearing Loss in a Cohort from Argentina: From Molecular Diagnosis to Pre-Clinical Research

Authors: Paula I. Buonfiglio, Carlos David Bruque, Lucia Salatino, Vanesa Lotersztein, Sebastián Menazzi, Paola Plazas, Ana Belén Elgoyhen, Viviana Dalamón

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Hearing loss (HL) is the most prevalent sensorineural disorder affecting about 10% of the global population, with more than half due to genetic causes. About 1 in 500-1000 newborns present congenital HL. Most of the patients are non-syndromic with an autosomal recessive mode of inheritance. To date, more than 100 genes are related to HL. Therefore, the Whole-exome sequencing (WES) technique has become a cost-effective alternative approach for molecular diagnosis. Nevertheless, new challenges arise from the detection of novel variants, in particular missense changes, which can lead to a spectrum of genotype-to-phenotype correlations, which is not always straightforward. In this work, we aimed to identify the genetic causes of HL in isolated and familial cases by designing a multistep approach to analyze target genes related to hearing impairment. Moreover, we performed in silico and in vivo analyses in order to further study the effect of some of the novel variants identified in the hair cell function using the zebrafish model. A total of 650 patients were studied by Sanger Sequencing and Gap-PCR in GJB2 and GJB6 genes, respectively, diagnosing 15.5% of sporadic cases and 36% of familial ones. Overall, 50 different sequence variants were detected. Fifty of the undiagnosed patients with moderate HL were tested for deletions in STRC gene by Multiplex ligation-dependent probe amplification technique (MLPA), leading to 6% of diagnosis. After this initial screening, 50 families were selected to be analyzed by WES, achieving diagnosis in 44% of them. Half of the identified variants were novel. A missense variant in MYO6 gene detected in a family with postlingual HL was selected to be further analyzed. A protein modeling with AlphaFold2 software was performed, proving its pathogenic effect. In order to functionally validate this novel variant, a knockdown phenotype rescue assay in zebrafish was carried out. Injection of wild-type MYO6 mRNA in embryos rescued the phenotype, whereas using the mutant MYO6 mRNA (carrying c.2782C>A variant) had no effect. These results strongly suggest the deleterious effect of this variant on the mobility of stereocilia in zebrafish neuromasts, and hence on the auditory system. In the present work, we demonstrated that our algorithm is suitable for the sequential multigenic approach to HL in our cohort. These results highlight the importance of a combined strategy in order to identify candidate variants as well as the in silico and in vivo studies to analyze and prove their pathogenicity and accomplish a better understanding of the mechanisms underlying the physiopathology of the hearing impairment.

Keywords: diagnosis, genetics, hearing loss, in silico analysis, in vivo analysis, WES, zebrafish

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470 An Integrated HCV Testing Model as a Method to Improve Identification and Linkage to Care in a Network of Community Health Centers in Philadelphia, PA

Authors: Catelyn Coyle, Helena Kwakwa

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Objective: As novel and better tolerated therapies become available, effective HCV testing and care models become increasingly necessary to not only identify individuals with active infection but also link them to HCV providers for medical evaluation and treatment. Our aim is to describe an effective HCV testing and linkage to care model piloted in a network of five community health centers located in Philadelphia, PA. Methods: In October 2012, National Nursing Centers Consortium piloted a routine opt-out HCV testing model in a network of community health centers, one of which treats HCV, HIV, and co-infected patients. Key aspects of the model were medical assistant initiated testing, the use of laboratory-based reflex test technology, and electronic medical record modifications to prompt, track, report and facilitate payment of test costs. Universal testing on all adult patients was implemented at health centers serving patients at high-risk for HCV. The other sites integrated high-risk based testing, where patients meeting one or more of the CDC testing recommendation risk factors or had a history of homelessness were eligible for HCV testing. Mid-course adjustments included the integration of dual HIV testing, development of a linkage to care coordinator position to facilitate the transition of HIV and/or HCV-positive patients from primary to specialist care, and the transition to universal HCV testing across all testing sites. Results: From October 2012 to June 2015, the health centers performed 7,730 HCV tests and identified 886 (11.5%) patients with a positive HCV-antibody test. Of those with positive HCV-antibody tests, 838 (94.6%) had an HCV-RNA confirmatory test and 590 (70.4%) progressed to current HCV infection (overall prevalence=7.6%); 524 (88.8%) received their RNA-positive test result; 429 (72.7%) were referred to an HCV care specialist and 271 (45.9%) were seen by the HCV care specialist. The best linkage to care results were seen at the test and treat the site, where of the 333 patients were current HCV infection, 175 (52.6%) were seen by an HCV care specialist. Of the patients with active HCV infection, 349 (59.2%) were unaware of their HCV-positive status at the time of diagnosis. Since the integration of dual HCV/HIV testing in September 2013, 9,506 HIV tests were performed, 85 (0.9%) patients had positive HIV tests, 81 (95.3%) received their confirmed HIV test result and 77 (90.6%) were linked to HIV care. Dual HCV/HIV testing increased the number of HCV tests performed by 362 between the 9 months preceding dual testing and first 9 months after dual testing integration, representing a 23.7% increment. Conclusion: Our HCV testing model shows that integrated routine testing and linkage to care is feasible and improved detection and linkage to care in a primary care setting. We found that prevalence of current HCV infection was higher than that seen in locally in Philadelphia and nationwide. Intensive linkage services can increase the number of patients who successfully navigate the HCV treatment cascade. The linkage to care coordinator position is an important position that acts as a trusted intermediary for patients being linked to care.

Keywords: HCV, routine testing, linkage to care, community health centers

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469 AI-Based Information System for Hygiene and Safety Management of Shared Kitchens

Authors: Jongtae Rhee, Sangkwon Han, Seungbin Ji, Junhyeong Park, Byeonghun Kim, Taekyung Kim, Byeonghyeon Jeon, Jiwoo Yang

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The shared kitchen is a concept that transfers the value of the sharing economy to the kitchen. It is a type of kitchen equipped with cooking facilities that allows multiple companies or chefs to share time and space and use it jointly. These shared kitchens provide economic benefits and convenience, such as reduced investment costs and rent, but also increase the risk of safety management, such as cross-contamination of food ingredients. Therefore, to manage the safety of food ingredients and finished products in a shared kitchen where several entities jointly use the kitchen and handle various types of food ingredients, it is critical to manage followings: the freshness of food ingredients, user hygiene and safety and cross-contamination of cooking equipment and facilities. In this study, it propose a machine learning-based system for hygiene safety and cross-contamination management, which are highly difficult to manage. User clothing management and user access management, which are most relevant to the hygiene and safety of shared kitchens, are solved through machine learning-based methodology, and cutting board usage management, which is most relevant to cross-contamination management, is implemented as an integrated safety management system based on artificial intelligence. First, to prevent cross-contamination of food ingredients, we use images collected through a real-time camera to determine whether the food ingredients match a given cutting board based on a real-time object detection model, YOLO v7. To manage the hygiene of user clothing, we use a camera-based facial recognition model to recognize the user, and real-time object detection model to determine whether a sanitary hat and mask are worn. In addition, to manage access for users qualified to enter the shared kitchen, we utilize machine learning based signature recognition module. By comparing the pairwise distance between the contract signature and the signature at the time of entrance to the shared kitchen, access permission is determined through a pre-trained signature verification model. These machine learning-based safety management tasks are integrated into a single information system, and each result is managed in an integrated database. Through this, users are warned of safety dangers through the tablet PC installed in the shared kitchen, and managers can track the cause of the sanitary and safety accidents. As a result of system integration analysis, real-time safety management services can be continuously provided by artificial intelligence, and machine learning-based methodologies are used for integrated safety management of shared kitchens that allows dynamic contracts among various users. By solving this problem, we were able to secure the feasibility and safety of the shared kitchen business.

Keywords: artificial intelligence, food safety, information system, safety management, shared kitchen

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468 Temporal Profile of Exercise-Induced Changes in Plasma Brain-Derived Neurotrophic Factor Levels of Schizophrenic Individuals

Authors: Caroline Lavratti, Pedro Dal Lago, Gustavo Reinaldo, Gilson Dorneles, Andreia Bard, Laira Fuhr, Daniela Pochmann, Alessandra Peres, Luciane Wagner, Viviane Elsner

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Approximately 1% of the world's population is affected by schizophrenia (SZ), a chronic and debilitating neurodevelopmental disorder. Among possible factors, reduced levels of Brain-derived neurotrophic factor (BDNF) has been recognized in physiopathogenesis and course of SZ. In this context, peripheral BDNF levels have been used as a biomarker in several clinical studies, since this neurotrophin is able to cross the blood-brain barrier in a bi-directional manner and seems to present a strong correlation with the central nervous system fluid levels. The patients with SZ usually adopts a sedentary lifestyle, which has been partly associated with the increase in obesity incidence rates, metabolic syndrome, type 2 diabetes and coronary heart disease. On the other hand, exercise, a non-invasive and low cost intervention, has been considered an important additional therapeutic option for this population, promoting benefits to physical and mental health. To our knowledge, few studies have been pointed out that the positive effects of exercise in SZ patients are mediated, at least in part, to enhanced levels of BDNF after training. However, these studies are focused on evaluating the effect of single bouts of exercise of chronic interventions, data concerning the short- and long-term exercise outcomes on BDNF are scarce. Therefore, this study aimed to evaluate the effect of a concurrent exercise protocol (CEP) on plasma BDNF levels of SZ patients in different time-points. Material and Methods: This study was approved by the Research Ethics Committee of the Centro Universitário Metodista do IPA (no 1.243.680/2015). The participants (n=15) were subbmited to the CEP during 90 days, 3 times a week for 60 minutes each session. In order to evaluate the short and long-term effects of exercise, blood samples were collected pre, 30, 60 and 90 days after the intervention began. Plasma BDNF levels were determined with the ELISA method, from Sigma-Aldrich commercial kit (catalog number RAB0026) according to manufacturer's instructions. Results: A remarkable increase on plasma BDNF levels at 90 days after training compared to baseline (p=0.006) and 30 days (p=0.007) values were observed. Conclusion: Our data are in agreement with several studies that show significant enhancement on BDNF levels in response to different exercise protocols in SZ individuals. We might suggest that BDNF upregulation after training in SZ patients acts in a dose-dependent manner, being more pronounced in response to chronic exposure. Acknowledgments: This work was supported by Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS)/Brazil.

Keywords: exercise, BDNF, schizophrenia, time-points

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467 A Case of Myelofibrosis-Related Arthropathy: A Rare and Underrecognized Entity

Authors: Geum Yeon Sim, Jasal Patel, Anand Kumthekar, Stanley Wainapel

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A 65-year-old right-hand dominant African-American man, formerly employed as a security guard, was referred to Rehabilitation Medicine with bilateral hand stiffness and weakness. His past medical history was only significant for myelofibrosis, diagnosed 4 years earlier, for which he was receiving scheduled blood transfusions. Approximately 2 years ago, he began to notice stiffness and swelling in his non-dominant hand that progressed to pain and decreased strength, limiting his hand function. Similar but milder symptoms developed in his right hand several months later. There was no history of prior injury or exposure to cold. Physical examination showed enlargement of metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints with finger flexion contractures, Swan-neck and Boutonniere deformities, and associated joint tenderness. Changes were more prominent in the left hand. X-rays showed mild osteoarthritis of several bilateral PIP joints. Anti-nuclear antibodies, rheumatoid factor, and cyclic citrullinated peptide antibodies were negative. MRI of the hand showed no erosions or synovitis. A rheumatology consultation was obtained, and the cause of his symptoms was attributed to myelofibrosis-related arthropathy with secondary osteoarthritis. The patient was tried on diclofenac cream and received a few courses of Occupational Therapy with limited functional improvement. Primary myelofibrosis (PMF) is a rare myeloproliferative neoplasm characterized by clonal proliferation of myeloid cells with variable morphologic maturity and hematopoietic efficiency. Rheumatic manifestations of malignancies include direct invasion, paraneoplastic presentations, secondary gout, or hypertrophic osteoarthropathy. PMF causes gradual bone marrow fibrosis with extramedullary metaplastic hematopoiesis in the liver, spleen, or lymph nodes. Musculoskeletal symptoms are not common and are not well described in the literature. The first reported case of myelofibrosis related arthritis was seronegative arthritis due to synovial invasion of myeloproliferative elements. Myelofibrosis has been associated with autoimmune diseases such as systemic lupus erythematosus, progressive systemic sclerosis, and rheumatoid arthritis. Gout has been reported in patients with myelofibrosis, and the underlying mechanism is thought to be related to the high turnover of nucleic acids that is greatly augmented in this disease. X-ray findings in these patients usually include erosive arthritis with synovitis. Treatment of underlying PMF is the treatment of choice, along with anti-inflammatory medications. Physicians should be cognizant of recognizing this rare entity in patients with PMF while maintaining clinical suspicion for more common causes of joint deformities, such as rheumatic diseases.

Keywords: myelofibrosis, arthritis, arthralgia, malignancy

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466 Legal Provisions on Child Pornography in Bangladesh: A Comparative Study on South Asian Landscape

Authors: Monira Nazmi Jahan, Nusrat Jahan Nishat

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'Child Pornography' is a sex crime that portrays illegal images and videos of a minor over the Internet and now has become a social concern with the increase of commission of this crime. The major objective of this paper is to identify and examine the laws relating to child pornography in Bangladesh and to compare this with other South Asian countries. In Bangladesh to prosecute under child pornography, provisions have been made in ‘Digital Security Act, 2018’ where it has been defined as involving child in areas of child sexuality or in sexuality and whoever commits the crime will be punished for 10 years imprisonment or 10 lac taka fine. In India, the crime is dealt with ‘The Protection of Children from Sexual Offences Act, 2012’ (POSCO) where the offenders for commission of this crime has been divided separately and has provision for punishments starting from three years to rigorous life imprisonment and shall also be liable to fine. In the Maldives, there is ‘Special Provisions Act to Deal with Child Sex Abuse Offenders, Act number 12/2009’. In this act it has been provided that a person is guilty of such an act if intentionally runs child prostitution, involves child in the creation of pornography or displays child’s sexual organ in pornography then shall be punished between 20 to 25 years of imprisonment. Nepal prosecutes this crime through ‘Act Relating to Children, 2018’ and the conviction of using child in prostitution or sexual services is imprisonment up to fifteen years and fine up to one hundred fifty thousand rupees. In Pakistan, child pornography is prosecuted with ‘Pakistan Penal Code Child Abuse Amendment Act, 2016’. This provides that one is guilty of this offence if he involves child with or without consent in such activities. It provides punishment for two to seven years of imprisonment or fine from two hundred thousand to seven hundred thousand rupees. In Bhutan child pornography is not explicitly addressed under the municipal laws. The Penal Code of Bhutan penalizes all kinds of pornography including child pornography under the provisions of computer pornography and the offence shall be a misdemeanor. Child Pornography is also prohibited under the ‘Child Care and Protection Act’. In Sri Lanka, ‘The Penal Code’ de facto criminalizes child prohibition and has a penalty of two to ten years and may also be liable to fine. The most shocking scenario exists in Afghanistan. There is no specific law for the protection of children from pornography, whereas this serious crime is present there. This paper will be conducted through a qualitative research method that is, the primary sources will be laws, and secondary sources will be journal articles and newspapers. The conclusion that can be drawn is except Afghanistan all other South Asian countries have laws for controlling this crime but still have loopholes. India has the most amended provisions. Nepal has no provision for fine, and Bhutan does not mention any specific punishment. Bangladesh compared to these countries, has a good piece of law; however, it also has space to broaden the laws for controlling child pornography.

Keywords: child abuse, child pornography, life imprisonment, penal code, South Asian countries

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465 Bone Mineralization in Children with Wilson’s Disease

Authors: Shiamaa Eltantawy, Gihan Sobhy, Alif Alaam

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Wilson disease, or hepatolenticular degeneration, is an autosomal recessive disease that results in excess copper buildup in the body. It primarily affects the liver and basal ganglia of the brain, but it can affect other organ systems. Musculoskeletal abnormalities, including premature osteoarthritis, skeletal deformity, and pathological bone fractures, can occasionally be found in WD patients with a hepatic or neurologic type. The aim was to assess the prevalence of osteoporosis and osteopenia in Wilson’s disease patients. This case-control study was conducted on ninety children recruited from the inpatient ward and outpatient clinic of the Paediatric Hepatology, Gastroenterology, and Nutrition department of the National Liver Institute at Menofia University, aged from 1 to 18 years. Males were 49, and females were 41. Children were divided into three groups: (Group I) consisted of thirty patients with WD; (Group II) consisted of thirty patients with chronic liver disease other than WD; (Group III) consisted of thirty age- and sex-matched healthy The exclusion criteria were patients with hyperparathyroidism, hyperthyroidism, renal failure, Cushing's syndrome, and patients on certain drugs such as chemotherapy, anticonvulsants, or steroids. All patients were subjected to the following: 1- Full history-taking and clinical examination. 2-Laboratory investigations: (FBC,ALT,AST,serum albumin, total protein, total serum bilirubin,direct bilirubin,alkaline phosphatase, prothrombin time, serum critine,parathyroid hormone, serum calcium, serum phosphrus). 3-Bone mineral density (BMD, gm/cm2) values were measured by dual-energy X-ray absorptiometry (DEXA). The results revealed that there was a highly statistically significant difference between the three groups regarding the DEXA scan, and there was no statistically significant difference between groups I and II, but the WD group had the lowest bone mineral density. The WD group had a large number of cases of osteopenia and osteoporosis, but there was no statistically significant difference with the group II mean, while a high statistically significant difference was found when compared to group III. In the WD group, there were 20 patients with osteopenia, 4 patients with osteoporosis, and 6 patients who were normal. The percentages were 66.7%, 13.3%, and 20%, respectively. Therefore, the largest number of cases in the WD group had osteopenia. There was no statistically significant difference found between WD patients on different treatment regimens regarding DEXA scan results (Z-Score). There was no statistically significant difference found between patients in the WD group (normal, osteopenic, or osteoporotic) regarding phosphorus (mg/dL), but there was a highly statistically significant difference found between them regarding ionised Ca (mmol/L). Therefore, there was a decrease in bone mineral density when the Ca level was decreased. In summary, Wilson disease is associated with bone demineralization. The largest number of cases in the WD group in our study had osteopenia (66.7%). Different treatment regimens (zinc monotherapy, Artamin, and zinc) as well as different laboratory parameters have no effect on bone mineralization in WD cases. Decreased ionised Ca is associated with low BMD in WD patients. Children with WD should be investigated for BMD.

Keywords: wilson disease, Bone mineral density, liver disease, osteoporosis

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464 Distribution and Ecological Risk Assessment of Trace Elements in Sediments along the Ganges River Estuary, India

Authors: Priyanka Mondal, Santosh K. Sarkar

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The present study investigated the spatiotemporal distribution and ecological risk assessment of trace elements of surface sediments (top 0 - 5 cm; grain size ≤ 0.63 µm) in relevance to sediment quality characteristics along the Ganges River Estuary, India. Sediment samples were collected during ebb tide from intertidal regions covering seven sampling sites of diverse environmental stresses. The elements were analyzed with the help of ICPAES. This positive, mixohaline, macro-tidal estuary has global significance contributing ecological and economic services. Presence of fine-clayey particle (47.03%) enhances the adsorption as well as transportation of trace elements. There is a remarkable inter-metallic variation (mg kg-1 dry weight) in the distribution pattern in the following manner: Al (31801± 15943) > Fe (23337± 7584) > Mn (461±147) > S(381±235) > Zn(54 ±18) > V(43 ±14) > Cr(39 ±15) > As (34±15) > Cu(27 ±11) > Ni (24 ±9) > Se (17 ±8) > Co(11 ±3) > Mo(10 ± 2) > Hg(0.02 ±0.01). An overall trend of enrichment of majority of trace elements was very much pronounced at the site Lot 8, ~ 35km upstream of the estuarine mouth. In contrast, the minimum concentration was recorded at site Gangasagar, mouth of the estuary, with high energy profile. The prevalent variations in trace element distribution are being liable for a set of cumulative factors such as hydrodynamic conditions, sediment dispersion pattern and textural variations as well as non-homogenous input of contaminants from point and non-point sources. In order to gain insight into the trace elements distribution, accumulation, and their pollution status, geoaccumulation index (Igeo) and enrichment factor (EF) were used. The Igeo indicated that surface sediments were moderately polluted with As (0.60) and Mo (1.30) and strongly contaminated with Se (4.0). The EF indicated severe pollution of Se (53.82) and significant pollution of As (4.05) and Mo (6.0) and indicated the influx of As, Mo and Se in sediments from anthropogenic sources (such as industrial and municipal sewage, atmospheric deposition, agricultural run-off, etc.). The significant role of the megacity Calcutta in relevance to the untreated sewage discharge, atmospheric inputs and other anthropogenic activities is worthwhile to mention. The ecological risk for different trace elements was evaluated using sediment quality guidelines, effects range low (ERL), and effect range median (ERM). The concentration of As, Cu and Ni at 100%, 43% and 86% of the sampling sites has exceeded the ERL value while none of the element concentration exceeded ERM. The potential ecological risk index values revealed that As at 14.3% of the sampling sites would pose relatively moderate risk to benthic organisms. The effective role of finer clay particles for trace element distribution was revealed by multivariate analysis. The authors strongly recommend regular monitoring emphasizing on accurate appraisal of the potential risk of trace elements for effective and sustainable management of this estuarine environment.

Keywords: pollution assessment, sediment contamination, sediment quality, trace elements

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463 Anisakidosis in Turkey: Serological Survey and Risk for Humans

Authors: E. Akdur Öztürk, F. İrvasa Bilgiç, A. Ludovisi , O. Gülbahar, D. Dirim Erdoğan, M. Korkmaz, M. Á. Gómez Morales

Abstract:

Anisakidosis is a zoonotic human fish-borne parasitic disease caused by accidental ingestion of anisakid third-stage larvae (L3) of members of the Anisakidae family present in infected marine fish or cephalopods. Infection with anisakid larvae can lead to gastric, intestinal, extra-gastrointestinal and gastroallergic forms of the disease. Anisakid parasites have been reported in almost all seas, particularly in the Mediterranean Sea. There is a remarkably high level of risk exposure to these zoonotic parasites as they are present in economically and ecologically important fish of Europe. Anisakid L3 larvae have been also detected in several fish species from the Aegean Sea. Turkey is a peninsular country surrounded by Black, Aegean and the Mediterranean Sea. In this country, fishing habit and fishery product consumption are highly common. In recent years, there was also an increase in the consumption of raw fish due to the increasing interest in the cuisine of the Far East countries. In different regions of Turkey, A. simplex (inMerluccius Merluccius Scomber japonicus, Trachurus mediterraneus, Sardina pilchardus, Engraulis encrasicolus, etc.), Anisakis spp., Contraceucum spp., Pseudoterronova spp. and, C. aduncum were identified as well. Although it is accepted both the presence of anisakid parasites in fish and fishery products in Turkey and the presence of Turkish people with allergic manifestations after fish consumption, there are no reports of human anisakiasis in this country. Given the high prevalence of anisakid parasites in the country, the absence of reports is likely not due to the absence of clinical cases rather to the unavailability of diagnostic tools and the low awareness of the presence of this infection. The aim of the study was to set up an IgE-Western Blot (WB) based test to detect the anisakidosis sensitization among Turkish people with a history of allergic manifestation related to fish consumption. To this end, crude worm antigens (CWA) and allergen enriched fraction (50-66% ) were prepared from L3 of A. simplex (s.l.) collected from Lepidopus caudatus fished in the Mediterranean Sea. These proteins were electrophoretically separated and transferred into the nitrocellulose membranes. By WB, specific proteins recognized by positive control serum samples from sensitized patients were visualized on nitrocellulose membranes by a colorimetric reaction. The CWA and 50–66% fraction showed specific bands, mainly due to Ani s 1 (20-22 kD) and Ani s 4 (9-10 kD). So far, a total of 7 serum samples from people with allergic manifestation and positive skin prick test (SPT) after fish consumption, have been tested and all of them resulted negative by WB, indicating the lack of sensitization to anisakids. This preliminary study allowed to set up a specific test and evidence the lack of correlation between both tests, SPT and WB. However, the sample size should be increased to estimate the anisakidosis burden in Turkish people.

Keywords: anisakidosis, fish parasite, serodiagnosis, Turkey

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462 Carbon Footprint of Educational Establishments: The Case of the University of Alicante

Authors: Maria R. Mula-Molina, Juan A. Ferriz-Papi

Abstract:

Environmental concerns are increasingly obtaining higher priority in sustainability agenda of educational establishments. This is important not only for its environmental performance in its own right as an organization, but also to present a model for its students. On the other hand, universities play an important role on research and innovative solutions for measuring, analyzing and reducing environmental impacts for different activities. The assessment and decision-making process during the activity of educational establishments is linked to the application of robust indicators. In this way, the carbon footprint is a developing indicator for sustainability that helps understand the direct impact on climate change. But it is not easy to implement. There is a large amount of considering factors involved that increases its complexity, such as different uses at the same time (research, lecturing, administration), different users (students, staff) or different levels of activity (lecturing, exam or holidays periods). The aim of this research is to develop a simplified methodology for calculating and comparing carbon emissions per user at university campus considering two main aspects for carbon accountings: Building operations and transport. Different methodologies applied in other Spanish university campuses are analyzed and compared to obtain a final proposal to be developed in this type of establishments. First, building operation calculation considers the different uses and energy sources consumed. Second, for transport calculation, the different users and working hours are calculated separately, as well as their origin and traveling preferences. For every transport, a different conversion factor is used depending on carbon emissions produced. The final result is obtained as an average of carbon emissions produced per user. A case study is applied to the University of Alicante campus in San Vicente del Raspeig (Spain), where the carbon footprint is calculated. While the building operation consumptions are known per building and month, it does not happen with transport. Only one survey about the habit of transport for users was developed in 2009/2010, so no evolution of results can be shown in this case. Besides, building operations are not split per use, as building services are not monitored separately. These results are analyzed in depth considering all factors and limitations. Besides, they are compared to other estimations in other campuses. Finally, the application of the presented methodology is also studied. The recommendations concluded in this study try to enhance carbon emission monitoring and control. A Carbon Action Plan is then a primary solution to be developed. On the other hand, the application developed in the University of Alicante campus cannot only further enhance the methodology itself, but also render the adoption by other educational establishments more readily possible and yet with a considerable degree of flexibility to cater for their specific requirements.

Keywords: building operations, built environment, carbon footprint, climate change, transport

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461 Teamwork on Innovation in Young Enterprises: A Qualitative Analysis

Authors: Polina Trusova

Abstract:

The majority of young enterprises is founded and run by teams and develops new, innovative products or services. While problems within the team are considered to be an important reason for the failure of young enterprises, effective teamwork on innovation may be a key success factor. It may require special teamwork design or members’ creativity not needed during work routine. However, little is known about how young enterprises develop innovative solutions in teams, what makes their teamwork special and what influences its effectivity. Extending this knowledge is essential for understanding the success and failure factors for young enterprises. Previous research focused on working on innovation or professional teams in general. Rare studies combining these issues usually concentrate on homogenous groups like IT expert teams in innovation projects of big, well-established firms. The transferability of those studies’ findings to the entrepreneurial context is doubtful because of several reasons why teamwork should differ significantly between big, well-established firms and young enterprises. First, teamwork is conducted by team members, e.g., employees. The personality of employees in young enterprises, in contrast to that of employees in established firms, has been shown to be more similar to the personality of entrepreneurs. As entrepreneurs were found to be more open to experience and show less risk aversion, it may have a positive impact on their teamwork. Persons open to novelty are more likely to develop or accept a creative solution, which is especially important for teamwork on innovation. Secondly, young enterprises are often characterized by a flat hierarchy, so in general, teamwork should be more participative there. It encourages each member (and not only the founder) to produce and discuss innovative ideas, increasing their variety and enabling the team to select the best idea from the larger idea pool. Thirdly, teams in young enterprises are often multidisciplinary. It has some advantages but also increases the risk of internal conflicts making teamwork less effective. Despite the key role of teamwork on innovation and presented barriers for transferring existing evidence to the context of young enterprises, only a few researchers have addressed this issue. In order to close the existing research gap, to explore and understand how innovations are developed in teams of young enterprises and which factors influencing teamwork may be especially relevant for such teams, a qualitative study has been developed. The study consisting of 20 half-structured interviews with (co-)founders of young innovative enterprises in the UK and USA started in September 2017. The interview guide comprises but is not limited to teamwork dimensions discussed in literature like members’ skill or authority differentiation. Data will be evaluated following the rules of qualitative content analysis. First results indicate some factors which may be relevant especially for teamwork in young innovative enterprises. They will enrich the scientific discussion and provide the evidence needed to test a possible causality between identified factors and teamwork effectivity in future research on young innovative enterprises. Results and their discussion can be presented at the conference.

Keywords: innovation, qualitative study, teamwork, young enterprises

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460 Prevalent Features of Human Infections with Highly Pathogenic Avian Influenza A(H7N9) Virus, China, 2017

Authors: Lei Zhou, Dan Li, Ruiqi Ren, Chao Li, Yali Wang, Daxin Ni, Zijian Feng, Timothy M. Uyeki, Qun Li

Abstract:

Since the first human infections with avian influenza A(H7N9) virus were identified in early 2013, 1533 cases of laboratory-confirmed A(H7N9) virus infections were reported and confirmed as of September 13, 2017. The fifth epidemic was defined as starting from September 1, 2016, and the number of A(H7N9) cases has surged since the end of December in 2016. On February 18, 2017, the A(H7N9) cases who were infected with highly pathogenic avian influenza (HPAI) virus was reported from Southern China. The HPAI A(H7N9) cases were identified and then an investigation and analyses were conducted to assess whether disease severity in humans has changed with HPAI A(H7N9) compared with low pathogenic avian influenza (LPAI) A(H7N9) virus infection. Methods: All confirmed cases with A(H7N9) virus infections reported throughout mainland China from September 1, 2016, to September 13, 2017, were included. Cases' information was extracted from field investigation reports and the notifiable infectious surveillance system to describe the demographic, clinical, and epidemiologic characteristics. Descriptive statistics were used to compare HPAI A(H7N9) cases with all LPAI A(H7N9) cases reported during the fifth epidemic. Results: A total of 27 cases of HPAI A(H7N9) virus were identified infection from five provinces, including Guangxi (44%), Guangdong (33%), Hunan (15%), Hebei (4%) and Shangxi (4%). The median age of cases of HPAI A(H7N9) virus infection was 60 years (range, 15 to 80) and most of them were male (59%) and lived in rural areas (78%). All 27 cases had live poultry related exposures within 10 days before their illness onset. In comparison with LPAI A(H7N9) case-patients, HPAI A(H7N9) case-patients were significantly more likely to live in rural areas (78% vs. 51%; p = 0.006), have exposure to the sick or dead poultry (56% vs. 19%; p = 0.000), and be hospitalized earlier (median 3 vs. 4 days; p = 0.007). No significant differences were observed in median age, sex, prevalence of underlying chronic medical conditions, median time from illness onset to first medical service seeking, starting antiviral treatment, and diagnosis. Although the median time from illness onset to death (9 vs. 13 days) was shorter and the overall case-fatality proportion (48% vs. 38%) was higher for HPAI A(H7N9) case-patients than for LPAI A(H7N9) case-patients, these differences were not statistically significant. Conclusions: Our findings indicate that HPAI A(H7N9) virus infection was associated with exposure to sick and dead poultry in rural areas when visited live poultry market or in the backyard. In the fifth epidemic in mainland China, HPAI A (H7N9) case-patients were hospitalized earlier than LPAI A(H7N9) case-patients. Although the difference was not statistically significant, the mortality of HPAI A (H7N9) case-patients was obviously higher than that of LPAI A(H7N9) case-patients, indicating a potential severity change of HPAI A(H7N9) virus infection.

Keywords: Avian influenza A (H7N9) virus, highly pathogenic avian influenza (HPAI), case-patients, poultry

Procedia PDF Downloads 147
459 A Web-Based Real Property Updating System for Efficient and Sustainable Urban Development: A Case Study in Ethiopia

Authors: Eyosiyas Aga

Abstract:

The development of information communication technology has transformed the paper-based mapping and land registration processes to a computerized and networked system. The computerization and networking of real property information system play a vital role in good governance and sustainable development of emerging countries through cost effective, easy and accessible service delivery for the customer. The efficient, transparent and sustainable real property system is becoming the basic infrastructure for the urban development thus improve the data management system and service delivery in the organizations. In Ethiopia, the real property administration is paper based as a result, it confronted problems of data management, illegal transactions, corruptions, and poor service delivery. In order to solve this problem and to facilitate real property market, the implementation of web-based real property updating system is crucial. A web-based real property updating is one of the automation (computerizations) methods to facilitate data sharing, reduce time and cost of the service delivery in real property administration system. In additions, it is useful for the integration of data onto different information systems and organizations. This system is designed by combining open source software which supported by open Geo-spatial consortium. The web-based system is mainly designed by using open source software with the help of open Geo-spatial Consortium. The Open Geo-spatial Consortium standards such as the Web Feature Service and Web Map Services are the most widely used standards to support and improves web-based real property updating. These features allow the integration of data from different sources, and it can be used to maintain consistency of data throughout transactions. The PostgreSQL and Geoserver are used to manage and connect a real property data to the flex viewer and user interface. The system is designed for both internal updating system (municipality); which is mainly updating of spatial and textual information, and the external system (customer) which focus on providing and interacting with the customer. This research assessed the potential of open source web applications and adopted this technology for real property updating system in Ethiopia through simple, cost effective and secured way. The system is designed by combining and customizing open source software to enhance the efficiency of the system in cost effective way. The existing workflow for real property updating is analyzed to identify the bottlenecks, and the new workflow is designed for the system. The requirement is identified through questionnaire and literature review, and the system is prototype for the study area. The research mainly aimed to integrate human resource with technology in designing of the system to reduce data inconsistency and security problems. In additions, the research reflects on the current situation of real property administration and contributions of effective data management system for efficient, transparent and sustainable urban development in Ethiopia.

Keywords: cadaster, real property, sustainable, transparency, web feature service, web map service

Procedia PDF Downloads 250
458 Elucidation of Dynamics of Murine Double Minute 2 Shed Light on the Anti-cancer Drug Development

Authors: Nigar Kantarci Carsibasi

Abstract:

Coarse-grained elastic network models, namely Gaussian network model (GNM) and Anisotropic network model (ANM), are utilized in order to investigate the fluctuation dynamics of Murine Double Minute 2 (MDM2), which is the native inhibitor of p53. Conformational dynamics of MDM2 are elucidated in unbound, p53 bound, and non-peptide small molecule inhibitor bound forms. With this, it is aimed to gain insights about the alterations brought to global dynamics of MDM2 by native peptide inhibitor p53, and two small molecule inhibitors (HDM201 and NVP-CGM097) that are undergoing clinical stages in cancer studies. MDM2 undergoes significant conformational changes upon inhibitor binding, carrying pieces of evidence of induced-fit mechanism. Small molecule inhibitors examined in this work exhibit similar fluctuation dynamics and characteristic mode shapes with p53 when complexed with MDM2, which would shed light on the design of novel small molecule inhibitors for cancer therapy. The results showed that residues Phe 19, Trp 23, Leu 26 reside in the minima of slowest modes of p53, pointing to the accepted three-finger binding model. Pro 27 displays the most significant hinge present in p53 and comes out to be another functionally important residue. Three distinct regions are identified in MDM2, for which significant conformational changes are observed upon binding. Regions I (residues 50-77) and III (residues 90-105) correspond to the binding interface of MDM2, including (α2, L2, and α4), which are stabilized during complex formation. Region II (residues 77-90) exhibits a large amplitude motion, being highly flexible, both in the absence and presence of p53 or other inhibitors. MDM2 exhibits a scattered profile in the fastest modes of motion, while binding of p53 and inhibitors puts restraints on MDM2 domains, clearly distinguishing the kinetically hot regions. Mode shape analysis revealed that the α4 domain controls the size of the cleft by keeping the cleft narrow in unbound MDM2; and open in the bound states for proper penetration and binding of p53 and inhibitors, which points to the induced-fit mechanism of p53 binding. P53 interacts with α2 and α4 in a synchronized manner. Collective modes are shifted upon inhibitor binding, i.e., second mode characteristic motion in MDM2-p53 complex is observed in the first mode of apo MDM2; however, apo and bound MDM2 exhibits similar features in the softest modes pointing to pre-existing modes facilitating the ligand binding. Although much higher amplitude motions are attained in the presence of non-peptide small molecule inhibitor molecules as compared to p53, they demonstrate close similarity. Hence, NVP-CGM097 and HDM201 succeed in mimicking the p53 behavior well. Elucidating how drug candidates alter the MDM2 global and conformational dynamics would shed light on the rational design of novel anticancer drugs.

Keywords: cancer, drug design, elastic network model, MDM2

Procedia PDF Downloads 115
457 Generating Ideas to Improve Road Intersections Using Design with Intent Approach

Authors: Omar Faruqe Hamim, M. Shamsul Hoque, Rich C. McIlroy, Katherine L. Plant, Neville A. Stanton

Abstract:

Road safety has become an alarming issue, especially in low-middle income developing countries. The traditional approaches lack the out of the box thinking, making engineers confined to applying usual techniques in making roads safer. A socio-technical approach has recently been introduced in improving road intersections through designing with intent. This Design With Intent (DWI) approach aims to give practitioners a more nuanced approach to design and behavior, working with people, people’s understanding, and the complexities of everyday human experience. It's a collection of design patterns —and a design and research approach— for exploring the interactions between design and people’s behavior across products, services, and environments, both digital and physical. Through this approach, it can be seen that how designing with people in behavior change can be applied to social and environmental problems, as well as commercially. It has a total of 101 cards across eight different lenses, such as architectural, error-proofing, interaction, ludic, perceptual, cognitive, Machiavellian, and security lens each having its own distinct characteristics of extracting ideas from the participant of this approach. For this research purpose, a three-legged accident blackspot intersection of a national highway has been chosen to perform the DWI workshop. Participants from varying fields such as civil engineering, naval architecture and marine engineering, urban and regional planning, and sociology actively participated for a day long workshop. While going through the workshops, the participants were given a preamble of the accident scenario and a brief overview of DWI approach. Design cards of varying lenses were distributed among 10 participants and given an hour and a half for brainstorming and generating ideas to improve the safety of the selected intersection. After the brainstorming session, the participants spontaneously went through roundtable discussions regarding the ideas they have come up with. According to consensus of the forum, ideas were accepted or rejected. These generated ideas were then synthesized and agglomerated to bring about an improvement scheme for the intersection selected in our study. To summarize the improvement ideas from DWI approach, color coding of traffic lanes for separate vehicles, channelizing the existing bare intersection, providing advance warning traffic signs, cautionary signs and educational signs motivating road users to drive safe, using textured surfaces at approach with rumble strips before the approach of intersection were the most significant one. The motive of this approach is to bring about new ideas from the road users and not just depend on traditional schemes to increase the efficiency, safety of roads as well and to ensure the compliance of road users since these features are being generated from the minds of users themselves.

Keywords: design with intent, road safety, human experience, behavior

Procedia PDF Downloads 124