Search results for: the school function assessment

Authors: Abdulaziz Bashir Kutawa, Khairulmazmi Ahmad, Mohd Zobir Hussein, Asgar Ali, Mohd Aswad Abdul Wahab, Amara Rafi, Mahesh Tiran Gunasena, Muhammad Ziaur Rahman, Md Imam Hossain, Syazwan Afif Mohd Zobir

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Various abiotic and biotic stresses have an impact on rice production all around the world. The most serious and prevalent disease in rice plants, known as rice blast, is one of the major obstacles to the production of rice. It is one of the diseases that has the greatest negative effects on rice farming globally, the disease is caused by a fungus called Magnaporthe grisae. Since nanoparticles were shown to have an inhibitory impact on certain types of fungus, nanotechnology is a novel notion to enhance agriculture by battling plant diseases. Utilizing nanocarrier systems enables the active chemicals to be absorbed, attached, and encapsulated to produce efficient nanodelivery formulations. The objectives of this research work were to determine the efficacy and mode of action of the nanofungicides (in-vitro) and in field conditions (in-vivo). Ionic gelation method was used in the development of the nanofungicides. Using the poisoned media method, the synthesized agronanofungicides' in-vitro antifungal activity was assessed against M. grisae. The potato dextrose agar (PDA) was amended in several concentrations; 0.001, 0.005, 0.01, 0.025, 0.05, 0.1, 0.15, 0.20, 0.25, 0.30, and 0.35 ppm for the nanofungicides. Medium with the only solvent served as a control. Every day, mycelial growth was measured, and PIRG (percentage inhibition of radial growth) was also computed. Every day, mycelial growth was measured, and PIRG (percentage inhibition of radial growth) was also computed. Based on the results of the zone of inhibition, the chitosan-hexaconazole agronanofungicide (2g/mL) was the most effective fungicide to inhibit the growth of the fungus with 100% inhibition at 0.2, 0.25, 0.30, and 0.35 ppm, respectively. Then followed by carbendazim analytical fungicide that inhibited the growth of the fungus (100%) at 5, 10, 25, 50, and 100 ppm, respectively. The least were found to be propiconazole and basamid fungicides with 100% inhibition only at 100 ppm. The scanning electron microscope (SEM), confocal laser scanning microscope (CLSM), and transmission electron microscope (TEM) were used to study the mechanisms of action of the M. grisae fungal cells. The results showed that both carbendazim, chitosan-hexaconazole, and HXE were found to be the most effective fungicides in disrupting the mycelia of the fungus, and internal structures of the fungal cells. The results of the field assessment showed that the CHDEN treatment (5g/L, double dosage) was found to be the most effective fungicide to reduce the intensity of the rice blast disease with DSI of 17.56%, lesion length (0.43 cm), DR of 82.44%, AUDPC of 260.54 Unit2, and PI of 65.33%, respectively. The least treatment was found to be chitosan-hexaconazole-dazomet (2.5g/L, MIC). The usage of CHDEN and CHEN nanofungicides will significantly assist in lessening the severity of rice blast in the fields, increasing output and profit for rice farmers.

Keywords: chitosan, hexaconazole, disease incidence, and magnaporthe grisae

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Authors: D. Pogliana, A. Maso, N. Milani, D. Panzin, S. Rivaroli, J. Konin

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This case aims to identify the role of movement quality during the final stage of return to sport (RTS) in a male amateur football player 13 years old after passing the acute phase of the bilateral Osgood-Schlatter disease (OSD). The patient, after a year from passing the acute phase of OSD with the abstention of physical activity, reports bilateral anterior knee pain at the beginning of the football sport activity. Interventions: After the orthopedist check, who recommended physiotherapy sessions for the correction of motor patterns and the isometric reinforcement of the muscles of the quadriceps, the rehabilitation intervention was developed in 7 weeks through 14 sessions of neuro-motor training (NMT) with a frequency of two weekly sessions and six sessions of muscle-strengthening with a frequency of one weekly session. The sessions of NMT were carried out through free body exercises (or with overloads) with visual bio-feedback with the help of two cameras (one with anterior vision and one with lateral vision of the subject) and a big touch screen. The aim of these sessions of NMT was to modify the dysfunctional motor patterns evaluated by the 2D motion analysis test. The test was carried out at the beginning and at the end of the rehabilitation course and included five movements: single-leg squat (SLS), drop jump (DJ), single-leg hop (SLH), lateral shuffle (LS), and change of direction (COD). Each of these movements was evaluated through the video analysis of dynamic valgus knee, pelvic tilt, trunk control, shock absorption, and motor strategy. A free image analysis software (Kinovea) was then used to calculate scores. Results: Baseline assessment of the subject showed a total score of 59% on the right limb and 64% on the left limb (considering an optimal score above 85%) with large deficits in shock absorption capabilities, the presence of dynamic valgus knee, and dysfunctional motor strategies defined “quadriceps dominant.” After six weeks of training, the subject achieved a total score of 80% on the right limb and 86% on the left limb, with significant improvements in shock absorption capabilities, the presence of dynamic knee valgus, and the employment of more hip-oriented motor strategies on both lower limbs. The improvements shown in dynamic knee valgus, greater hip-oriented motor strategies, and improved shock absorption identified through six weeks of the NMT program can help a teenager amateur football player to manage the anterior knee pain during sports activity. In conclusion, NMT was a good choice to help a 13 years old male amateur football player to return to performance without pain after OSD and can also be used with all this type of athletes of the other teams' sports.

Keywords: movement analysis, neuro-motor training, knee pain, movement strategies

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Authors: Adriana de Paula Lacerda Santos, Bruna Godke, Mauro Lacerda Santos Filho

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Several dams in the world have already collapsed, causing environmental, social and economic damage. The concern to avoid future disasters has stimulated the creation of a great number of laws and rules in many countries. In Brazil, Law 12.334/2010 was created, which establishes the National Policy on Dam Safety. Overall, this policy requires the dam owners to invest in the maintenance of their structures and to improve its monitoring systems in order to provide faster and straightforward responses in the case of an increase of risks. As monitoring tools, visual inspections has provides comprehensive assessment of the structures performance, while auscultation’s instrumentation has added specific information on operational or behavioral changes, providing an alarm when a performance indicator exceeds the acceptable limits. These limits can be set using statistical methods based on the relationship between instruments measures and other variables, such as reservoir level, time of the year or others instruments measuring. Besides the design parameters (uplift of the foundation, displacements, etc.) the dam instrumentation can also be used to monitor the behavior of defects and damage manifestations. Specifically in concrete gravity dams, one of the main causes for the appearance of cracks, are the concrete volumetric changes generated by the thermal origin phenomena, which are associated with the construction process of these structures. Based on this, the goal of this research is to propose a monitoring process of the thermal cracking behavior in concrete gravity dams, through the instrumentation data analysis and the establishment of control values. Therefore, as a case study was selected the Block B-11 of José Richa Governor Dam Power Plant, that presents a cracking process, which was identified even before filling the reservoir in August’ 1998, and where crack meters and surface thermometers were installed for its monitoring. Although these instruments were installed in May 2004, the research was restricted to study the last 4.5 years (June 2010 to November 2014), when all the instruments were calibrated and producing reliable data. The adopted method is based on simple linear correlations procedures to understand the interactions among the instruments time series, verifying the response times between them. The scatter plots were drafted from the best correlations, which supported the definition of the limit control values. Among the conclusions, it is shown that there is a strong or very strong correlation between ambient temperature and the crack meters and flowmeters measurements. Based on the results of the statistical analysis, it was possible to develop a tool for monitoring the behavior of the case study cracks. Thus it was fulfilled the goal of the research to develop a proposal for a monitoring process of the behavior of thermal cracking in concrete gravity dams.

Keywords: concrete gravity dam, dams safety, instrumentation, simple linear correlation

Procedia PDF Downloads 292

Authors: Eyob Seife

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Immunization is a life-saving intervention which prevents needless suffering through sickness, disability, and death. Emphasis on data quality and use will become even stronger with the development of the immunization agenda 2030 (IA2030). Quality of data is a key factor in generating reliable health information that enables monitoring progress, financial planning, vaccine forecasting capacities, and making decisions for continuous improvement of the national immunization program. However, ensuring data of sufficient quality and promoting an information-use culture at the point of the collection remains critical and challenging, especially in hard-to-reach and pastoralist areas where Degehabur district is selected based on a hypothesis of ‘there is no difference in reported and recounted immunization data consistency. Data quality is dependent on different factors where organizational, behavioral, technical, and contextual factors are the mentioned ones. A cross-sectional quantitative study was conducted on September 2022 in the Degehabur district. The study used the world health organization (WHO) recommended data quality self-assessment (DQS) tools. Immunization tally sheets, registers, and reporting documents were reviewed at 5 health facilities (2 health centers and 3 health posts) of primary health care units for one fiscal year (12 months) to determine the accuracy ratio. The data was collected by trained DQS assessors to explore the quality of monitoring systems at health posts, health centers, and the district health office. A quality index (QI) was assessed, and the accuracy ratio formulated were: the first and third doses of pentavalent vaccines, fully immunized (FI), and the first dose of measles-containing vaccines (MCV). In this study, facility-level results showed both over-reporting and under-reporting were observed at health posts when computing the accuracy ratio of the tally sheet to health post reports found at health centers for almost all antigens verified where pentavalent 1 was 88.3%, 60.4%, and 125.6% for Health posts A, B, and C respectively. For first-dose measles-containing vaccines (MCV), similarly, the accuracy ratio was found to be 126.6%, 42.6%, and 140.9% for Health posts A, B, and C, respectively. The accuracy ratio for fully immunized children also showed 0% for health posts A and B and 100% for health post-C. A relatively better accuracy ratio was seen at health centers where the first pentavalent dose was 97.4% and 103.3% for health centers A and B, while a first dose of measles-containing vaccines (MCV) was 89.2% and 100.9% for health centers A and B, respectively. A quality index (QI) of all facilities also showed results between the maximum of 33.33% and a minimum of 0%. Most of the verified immunization data accuracy ratios were found to be relatively better at the health center level. However, the quality of the monitoring system is poor at all levels, besides poor data accuracy at all health posts. So attention should be given to improving the capacity of staff and quality of monitoring system components, namely recording, reporting, archiving, data analysis, and using information for decision at all levels, especially in pastoralist areas where such kinds of study findings need to be improved beside to improving the data quality at root and health posts level.

Keywords: accuracy ratio, Degehabur District, regular childhood immunization program, quality of monitoring system, Somali Region-Ethiopia

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Authors: Zia Ul Haq, Saleem Muhammad, Naeem Ullah, Abbas Shah, Abdullah Shah

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Pakistan being the developing country is facing double burden of communicable and non-communicable disease. The aspect of secondary prevention of ischemic heart disease in developing countries is the dire need for public health specialists, clinicians and policy makers. There is some evidence that psychotherapeutic measures, including psychotherapy, recreation, exercise and stress management training have positive impact on secondary prevention of cardiovascular diseases but there are some contradictory findings as well. Cardiac rehabilitation program (CRP) has not yet fully implemented in Pakistan. Psychological, physical and specific health-related quality of life (HRQoL) outcomes needs assessment with respect to its practicality, effectiveness, and success. Objectives: To determine the effect of cardiac rehabilitation program (CRP) on the health-related quality of life (HRQoL) measures of post MI patients compared to the usual care. Hypothesis: Post MI patients who receive the interventions (CRP) will have better HRQoL as compared to those who receive the usual cares. Methods: The randomized control trial was conducted at a Cardiac Rehabilitation Unit of Lady Reading Hospital (LRH), Peshawar. LRH is the biggest hospital of the Province Khyber Pakhtunkhwa (KP). A total 206 participants who had recent first myocardial infarction were inducted in the study. Participants were randomly allocated into two group i.e. usual care group (UCG) and cardiac rehabilitation group (CRG) by permuted-block randomization (PBR) method. CRP was conducted in CRG in two phases. Three HRQoL outcomes i.e. general health questionnaire (GHQ), self-rated health (SRH) and MacNew quality of life after myocardial infarction (MacNew QLMI) were assessed at baseline and follow-up visits among both groups. Data were entered and analyzed by appropriate statistical test in STATA version 12. Results: A total of 195 participants were assessed at the follow-up period due to lost-to-follow-up. The mean age of the participants was 53.66 + 8.3 years. Males were dominant in both groups i.e. 150 (76.92%). Regarding educational status, majority of the participants were illiterate in both groups i.e. 128 (65.64%). Surprisingly, there were 139 (71.28%) who were non-smoker on the whole. The comorbid status was positive in 120 (61.54%) among all the patients. The SRH at follow-up among UCG and CRG was 4.06 (95% CI: 3.93, 4.19) and 2.36 (95% CI: 2.2, 2.52) respectively (p<0.001). GHQ at the follow-up of UCG and CRG was 20.91 (95% CI: 18.83, 21.97) and 7.43 (95% CI: 6.59, 8.27) respectively (p<0.001). The MacNew QLMI at follow-up of UCG and CRG was 3.82 (95% CI: 3.7, 3.94) and 5.62 (95% CI: 5.5, 5.74) respectively (p<0.001). All the HRQoL measures showed strongly significant improvement in the CRG at follow-up period. Conclusion: HRQOL improved in post MI patients after comprehensive CRP. Education of the patients and their supervision is needed when they are involved in their rehabilitation activities. It is concluded that establishing CRP in cardiac units, recruiting post-discharged MI patients and offering them CRP does not impose high costs and can result in significant improvement in HRQoL measures. Trial registration no: ACTRN12617000832370

Keywords: cardiovascular diseases, cardiac rehabilitation, health-related quality of life, HRQoL, myocardial infarction, quality of life, QoL, rehabilitation, randomized control trial

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Authors: Marita Pigłowska, Beata Kurc, Maciej Galiński

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The application of carbon materials in the branches of the electrochemical industry shows an increasing tendency each year due to the many interesting properties they possess. These are, among others, a well-developed specific surface, porosity, high sorption capacity, good adsorption properties, low bulk density, electrical conductivity and chemical resistance. All these properties allow for their effective use, among others in supercapacitors, which can store electric charges of the order of 100 F due to carbon electrodes constituting the capacitor plates. Coals (including expanded graphite, carbon black, graphite carbon fibers, activated carbon) are commonly used in electrochemical methods of removing oil derivatives from water after tanker disasters, e.g. phenols and their derivatives by their electrochemical anodic oxidation. Phenol can occupy practically the entire surface of carbon material and leave the water clean of hydrophobic impurities. Regeneration of such electrodes is also not complicated, it is carried out by electrochemical methods consisting in unblocking the pores and reducing resistances, and thus their reactivation for subsequent adsorption processes. Graphite is commonly used as an anode material in lithium-ion cells, while due to the limited capacity it offers (372 mAh g-1), new solutions are sought that meet both capacitive, efficiency and economic criteria. Increasingly, biodegradable materials, green materials, biomass, waste (including agricultural waste) are used in order to reuse them and reduce greenhouse effects and, above all, to meet the biodegradability criterion necessary for the production of lithium-ion cells as chemical power sources. The most common of these materials are cellulose, starch, wheat, rice, and corn waste, e.g. from agricultural, paper and pharmaceutical production. Such products are subjected to appropriate treatments depending on the desired application (including chemical, thermal, electrochemical). Starch is a biodegradable polysaccharide that consists of polymeric units such as amylose and amylopectin that build an ordered (linear) and amorphous (branched) structure of the polymer. Carbon is also used as a catalyst. Elemental carbon has become available in many nano-structured forms representing the hybridization combinations found in the primary carbon allotropes, and the materials can be enriched with a large number of surface functional groups. There are many examples of catalytic applications of coal in the literature, but the development of this field has been hampered by the lack of a conceptual approach combining structure and function and a lack of understanding of material synthesis. In the context of catalytic applications, the integrity of carbon environmental management properties and parameters such as metal conductivity range and bond sequence management should be characterized. Such data, along with surface and textured information, can form the basis for the provision of network support services.

Keywords: carbon materials, catalysis, BET, capacitors, lithium ion cell

Procedia PDF Downloads 174

Authors: Emmanuel A. David, Rebecca O. Soremekun, Roseline I. Aderemi-Williams

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Background: The complexities involved in the management of diabetes mellitus require a multi-dimensional, multi-professional collaborative and continuous care by health care providers and a substantial self-care by the patients in order to achieve desired treatment outcomes. The effect of pharmacists’ care in the management of diabetes in resource-endowed nations is well documented in literature, but randomised-controlled assessment of the impact of pharmacist-led care among patients with diabetes in resource-limited settings like Nigeria and sub-Saharan Africa countries is scarce. Objective: To evaluate the impact of Pharmacist-led care on glycaemic control in patients with uncontrolled type 2 diabetes, using a randomised-controlled study design Methods: This study employed a prospective randomised controlled design, to assess the impact of pharmacist-led care on glycaemic control of 108 poorly controlled type 2 diabetic patients. A total of 200 clinically diagnosed type 2 diabetes patients were purposively selected using fasting blood glucose ≥ 7mmol/L and tested for long term glucose control using Glycated haemoglobin measure. One hundred and eight (108) patients with ≥ 7% Glycated haemoglobin were recruited for the study and assigned unique identification numbers. They were further randomly allocated to intervention and usual care groups using computer generated random numbers, with each group containing 54 subjects. Patients in the intervention group received pharmacist-structured intervention, including education, periodic phone calls, adherence counselling, referral and 6 months follow-up, while patients in usual care group only kept clinic appointments with their physicians. Data collected at baseline and six months included socio-demographic characteristics, fasting blood glucose, Glycated haemoglobin, blood pressure, lipid profile. With an intention to treat analysis, Mann-Whitney U test was used to compared median change from baseline in the primary outcome (Glycated haemoglobin) and secondary outcomes measure, effect size was computed and proportion of patients that reached target laboratory parameter were compared in both arms. Results: All enrolled participants (108) completed the study, 54 in each study. Mean age was 51±11.75 and majority were female (68.5%). Intervention patients had significant reduction in Glycated haemoglobin (-0.75%; P<0.001; η2 = 0.144), with greater proportion attaining target laboratory parameter after 6 months of care compared to usual care group (Glycated haemoglobin: 42.6% vs 20.8%; P=0.02). Furthermore, patients who received pharmacist-led care were about 3 times more likely to have better glucose control (AOR 2.718, 95%CI: 1.143-6.461) compared to usual care group. Conclusion: Pharmacist-led care significantly improved glucose control in patients with uncontrolled type 2 diabetes mellitus and should be integrated in the routine management of diabetes patients, especially in resource-limited settings.

Keywords: glycaemic control , pharmacist-led care, randomised-controlled trial , type 2 diabetes mellitus

Procedia PDF Downloads 120

Authors: J. A. N. Sandamali, R. P. Hewawasam, K. A. P. W. Jayatilaka, L. K. B. Mudduwa

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Introduction: Doxorubicin is widely used in the treatment of solid organ tumors and hematological malignancies, but the dose-dependent cardiotoxicity due to free radical formation compromises its clinical utility. Therapeutic strategies which enhance cellular endogenous defense systems have been identified as promising approaches to combat oxidative stress-associated conditions. Cinnamomum zeylanicum (Ceylon cinnamon) has a number antioxidant compounds, which can effectively scavenge reactive oxygen including superoxide anions, hydroxyl radicals and as well as other free radicals. Therefore, the objective of the study was to elucidate the most effective dose of Cinnamomum bark extract which ameliorates doxorubicin-induced cardiotoxicity. Materials and methods: Wistar rats were divided into seven groups of 10 animals in each. Group 1: normal control (distilled water, orally, for 14 days, 10 mL/kg saline, ip, after 16 hours fast on the 11th day); Group 2: doxorubicin control (distilled water, orally, for 14 days, 18 mg/kg doxorubicin, ip, after 16 hour fast on the 11th day); Groups 3-7: five doses of freeze dried aqueous bark extracts (0.125, 0.25, 0.5, 1.0, 2.0g/kg, orally, daily for 14 days, 18 mg/kg doxorubicin, ip, after 16 hours fast on the 11th day). Animals were sacrificed on the 15th day and blood was collected for the estimation of cardiac troponin I (cTnI), AST and LDH concentrations and myocardial tissues were collected for histopathological assessment of myocardial damage and irreversible changes were graded by developing a score. Results: cTnI concentration of groups 1-7 were 0, 161.9, 128.6, 95.9, 38, 19.41 & 12.36 pg/mL showing significant differences (p<0.05) between group 2 and groups 4-7. In groups 1-7, serum AST concentration were 26.82, 68.1, 37.18, 36.23, 26.8, 26.62 & 22.43U/L and LDH concentrations were 1166.13, 2428.84, 1658.35, 1474.34, 1277.58, 1110.21 & 974.40U/L and a significant difference (p<0.05) was observed between group 2 and groups 3-7. The maximum score for myocardial necrosis was observed in group 2. Parallel to the increase of the dosage of plant extract, a gradual reduction of the score for myocardial necrosis was observed in groups 3-7. Reversible histological changes such as vacuolation, congestion were observed in group 2 and all plant treated groups. Haemorrhages, inflammatory cell infiltrations, and interstitial oedema were observed in group 2, but absent in groups treated with higher doses of the plant extract. Discussion & Conclusion: According to the in vitro antioxidant assays performed, Cinnamomum zeylanicum (Ceylon cinnamon) bark possesses high amounts of polyphenolic substances and high antioxidant activity. The present study showed that Cinnamomum zeylanicum extract at 2.0 g/kg possesses the most significant cardioprotective effect against doxorubicin-induced cardiotoxicity. It can be postulated that pretreatment with Cinnamomum bark extract may replenish the cardiomyocytes with antioxidants that are needed for the defense against oxidative stress induced by doxorubicin.

Keywords: cardioprotection, Cinnamomum zeylanicum, doxorubicin, free radicals

Procedia PDF Downloads 162

Authors: Maryamsadat Habibi

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Objective: pharmaceutical errors are avoidable occurrences that can result in inappropriate pharmaceutical use, patient harm, treatment failure, increased hospital costs and length of stay, and other outcomes that affect both the individual receiving treatment and the healthcare provider. This study aimed to perform a reconciliation of medications in the cardiovascular ward of Imam Reza Hospital in Mashhad, Iran, and evaluate the prevalence of medication discrepancies between the best medication list created for the patient by the pharmacist and the medication order of the treating physician there. Materials & Methods: The 97 patients in the cardiovascular ward of the Imam Reza Hospital in Mashhad were the subject of a cross-sectional study from June to September of 2021. After giving their informed consent and being admitted to the ward, all patients with at least one underlying condition and at least two medications being taken at home were included in the study. A medical reconciliation form was used to record patient demographics and medical histories during the first 24 hours of admission, and the information was contrasted with the doctors' orders. The doctor then discovered medication inconsistencies between the two lists and double-checked them to separate the intentional from the accidental anomalies. Finally, using SPSS software version 22, it was determined how common medical discrepancies are and how different sorts of discrepancies relate to various variables. Results: The average age of the participants in this study was 57.6915.84 years, with 57.7% of men and 42.3% of women. 95.9% of the patients among these people encountered at least one medication discrepancy, and 58.9% of them suffered at least one unintentional drug cessation. Out of the 659 medications registered in the study, 399 cases (60.54%) had inconsistencies, of which 161 cases (40.35%) involved the intentional stopping of a medication, 123 cases (30.82%) involved the stopping of a medication unintentionally, and 115 cases (28.82%) involved the continued use of a medication by adjusting the dose. Additionally, the category of cardiovascular pharmaceuticals and the category of gastrointestinal medications were found to have the highest medical inconsistencies in the current study. Furthermore, there was no correlation between the frequency of medical discrepancies and the following variables: age, ward, date of visit, type, and number of underlying diseases (P=0.13), P=0.61, P=0.72, P=0.82, P=0.44, and so forth. On the other hand, there was a statistically significant correlation between the number of medications taken at home (P=0.037) and the prevalence of medical discrepancies with gender (P=0.029). The results of this study revealed that 96% of patients admitted to the cardiovascular unit at Imam Reza Hospital had at least one medication error, which was typically an intentional drug discontinuance. According to the study's findings, patients admitted to Imam Reza Hospital's cardiovascular ward have a great potential for identifying and correcting various medication discrepancies as well as for avoiding prescription errors when the medication reconciliation method is used. As a result, it is essential to carry out a precise assessment to achieve the best treatment outcomes and avoid unintended medication discontinuation, unwanted drug-related events, and drug interactions between the patient's home medications and those prescribed in the hospital.

Keywords: drug combination, drug side effects, drug incompatibility, cardiovascular department

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Authors: Panaya Sudta, Wanchalerm Patanacharoenwong, Prachya Bumrungkun

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As With the evolution of smart grids, ensuring the reliability and efficiency of electrical systems in smart cities has become crucial. This paper proposes a distinct approach that combines advanced machine learning techniques to accurately predict electrical failures and address voltage reliability issues. This approach aims to improve the accuracy and efficiency of reliability evaluations in smart cities. The aim of this research is to develop a comprehensive predictive model that accurately predicts electrical failures and voltage reliability in smart cities. This model integrates RFM analysis, K-means clustering, and LSTM networks to achieve this objective. The research utilizes RFM analysis, traditionally used in customer value assessment, to categorize and analyze electrical components based on their failure recency, frequency, and monetary impact. K-means clustering is employed to segment electrical components into distinct groups with similar characteristics and failure patterns. LSTM networks are used to capture the temporal dependencies and patterns in customer data. This integration of RFM, K-means, and LSTM results in a robust predictive tool for electrical failures and voltage reliability. The proposed model has been tested and validated on diverse electrical utility datasets. The results show a significant improvement in prediction accuracy and reliability compared to traditional methods, achieving an accuracy of 92.78% and an F1-score of 0.83. This research contributes to the proactive maintenance and optimization of electrical infrastructures in smart cities. It also enhances overall energy management and sustainability. The integration of advanced machine learning techniques in the predictive model demonstrates the potential for transforming the landscape of electrical system management within smart cities. The research utilizes diverse electrical utility datasets to develop and validate the predictive model. RFM analysis, K-means clustering, and LSTM networks are applied to these datasets to analyze and predict electrical failures and voltage reliability. The research addresses the question of how accurately electrical failures and voltage reliability can be predicted in smart cities. It also investigates the effectiveness of integrating RFM analysis, K-means clustering, and LSTM networks in achieving this goal. The proposed approach presents a distinct, efficient, and effective solution for predicting and mitigating electrical failures and voltage issues in smart cities. It significantly improves prediction accuracy and reliability compared to traditional methods. This advancement contributes to the proactive maintenance and optimization of electrical infrastructures, overall energy management, and sustainability in smart cities.

Keywords: electrical state prediction, smart grids, data-driven method, long short-term memory, RFM, k-means, machine learning

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Authors: Muhammad Qasim, Laura Minet

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Victoria (BC), Canada, is a major cruise ship destination, attracting over 600,000 tourists annually. Residents of the James Bay neighborhood, home to the Ogden Point cruise terminal, have expressed concerns about the impacts of cruise ship activity on local traffic, air pollution, and safety compliance. This study evaluates the effects of cruise ship-induced traffic in James Bay, focusing on traffic flow intensification, density surges, changes in traffic mix, and speeding violations. To achieve these objectives, traffic data was collected in James Bay during two key periods: May, before the peak cruise season, and August, during full cruise operations. Three Miovision cameras captured the vehicular traffic mix at strategic entry points, while nine traffic counters monitored traffic distribution and speeding violations across the network. Traffic data indicated an average volume of 308 vehicles per hour during peak cruise times in May, compared to 116 vehicles per hour when no ships were in port. Preliminary analyses revealed a significant intensification of traffic flow during cruise ship "hoteling hours," with a volume increase of approximately 10% per cruise ship arrival. A notable 86% surge in taxi presence was observed on days with three cruise ships in port, indicating a substantial shift in traffic composition, particularly near the cruise terminal. The number of tourist buses escalated from zero in May to 32 in August, significantly altering traffic dynamics within the neighborhood. The period between 8 pm and 11 pm saw the most significant increases in traffic volume, especially when three ships were docked. Higher vehicle volumes were associated with a rise in speed violations, although this pattern was inconsistent across all areas. Speeding violations were more frequent on roads with lower traffic density, while roads with higher traffic density experienced fewer violations, due to reduced opportunities for speeding in congested conditions. PTV VISUM software was utilized for fuzzy distribution analysis and to visualize traffic distribution across the study area, including an assessment of the Level of Service on major roads during periods before and during the cruise ship season. This analysis identified the areas most affected by cruise ship-induced traffic, providing a detailed understanding of the impact on specific parts of the transportation network. These findings underscore the significant influence of cruise ship activity on traffic dynamics in Victoria, BC, particularly during peak periods when multiple ships are in port. The study highlights the need for targeted traffic management strategies to mitigate the adverse effects of increased traffic flow, changes in traffic mix, and speed violations, thereby enhancing road safety in the James Bay neighborhood. Further research will focus on detailed emissions estimation to fully understand the environmental impacts of cruise ship activity in Victoria.

Keywords: cruise ship tourism, air quality, traffic violations, transport dynamics, pollution

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Authors: María-Luisa Pinto-Salamanca, Wilson-Javier Pérez-Holguín

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Reconstruction of contact forces is a fundamental technique for analyzing the properties of a touched object and is essential for regulating the grip force in slip control loops. This is based on the processing of the distribution, intensity, and direction of the forces during the capture of the sensors. Currently, efficient hardware alternatives have been used more frequently in different fields of application, allowing the implementation of computationally complex algorithms, as is the case with tactile signal processing. The use of hardware for smart tactile sensing systems is a research area that promises to improve the processing time and portability requirements of applications such as artificial skin and robotics, among others. The literature review shows that hardware implementations are present today in almost all stages of smart tactile detection systems except in the force reconstruction process, a stage in which they have been less applied. This work presents a hardware implementation of a model-driven reported in the literature for the contact force reconstruction of flat and rigid tactile sensor arrays from normal stress data. From the analysis of a software implementation of such a model, this implementation proposes the parallelization of tasks that facilitate the execution of matrix operations and a two-dimensional optimization function to obtain a vector force by each taxel in the array. This work seeks to take advantage of the parallel hardware characteristics of Field Programmable Gate Arrays, FPGAs, and the possibility of applying appropriate techniques for algorithms parallelization using as a guide the rules of generalization, efficiency, and scalability in the tactile decoding process and considering the low latency, low power consumption, and real-time execution as the main parameters of design. The results show a maximum estimation error of 32% in the tangential forces and 22% in the normal forces with respect to the simulation by the Finite Element Modeling (FEM) technique of Hertzian and non-Hertzian contact events, over sensor arrays of 10×10 taxels of different sizes. The hardware implementation was carried out on an MPSoC XCZU9EG-2FFVB1156 platform of Xilinx® that allows the reconstruction of force vectors following a scalable approach, from the information captured by means of tactile sensor arrays composed of up to 48 × 48 taxels that use various transduction technologies. The proposed implementation demonstrates a reduction in estimation time of x / 180 compared to software implementations. Despite the relatively high values of the estimation errors, the information provided by this implementation on the tangential and normal tractions and the triaxial reconstruction of forces allows to adequately reconstruct the tactile properties of the touched object, which are similar to those obtained in the software implementation and in the two FEM simulations taken as reference. Although errors could be reduced, the proposed implementation is useful for decoding contact forces for portable tactile sensing systems, thus helping to expand electronic skin applications in robotic and biomedical contexts.

Keywords: contact forces reconstruction, forces estimation, tactile sensor array, hardware implementation

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Authors: N. Uaphongsathorn, C. Worawong, S. Thaewpia

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Background and significance: The population is aging in Thai society, the elderly dependent is at great risk of various functional, psychological, and socio-economic problems as well as less access to health care. They may require long term care at home to maximize their functional abilities and activities of daily living and to improve their quality of life during their own age. Therefore, there is a need to develop a home-based long term care to meet the long term care needs of elders dependent. Methods: The research purpose was to develop long term care model among the elderly dependent in Chaiyaphum province in Northeast region of Thailand. Action Research which is composing of planning, action, observation, and reflection phases was used. Research was carried out for 12 months in all sub-districts of 6 districts in Chaiyaphum province. Participants (N = 1,010) participating in the processes of model development were comprised of 3 groups: a) a total of 110 health care professionals, b) a total of 600 health volunteers and family caregivers and c) a total of 300 the elderly dependent with chronically medical illnesses or disabilities. Descriptive statistics and content analysis were used to analyze data. Findings: Results have shown that the most common health problems among elders dependent with physical disabilities to function independently were cardiovascular disease, dementia, and traffic injuries. The development of home-based long term care model among elders dependent in Chaiyaphum province was composed of six key steps. They are: a) initiating policies supporting formal and informal caregivers for the elder dependent in all sub-districts, b) building network and multidisciplinary team, c) developing 3-day care manager training program and 3-day care provider training program d) training case managers and care providers for the elderly dependent through team and action learning, e) assessing, planning and providing care based on care individual’s needs of the elderly dependent, and f) sharing experiences for good practice and innovation for long term care at homes in district urban and rural areas. Among all care managers and care providers, the satisfaction level for training programs was high with a mean score of 3.98 out of 5. The elders dependent and family caregivers addressed that long term care at home could contribute to improving life’s daily activities, family relationship, health status, and quality of life. Family caregivers and volunteers have feeling a sense of personal satisfaction and experiencing providing meaningful care and support for elders dependent. Conclusion: In conclusion, a home-based long term care is important to Thai elders dependent. Care managers and care providers play a large role and responsibility to provide appropriate care to meet the elders’ needs in both urban and rural areas in Thai society. Further research could be rigorously studied with a larger group of populations in similar socio-economic and cultural contexts.

Keywords: elderly people, care manager, care provider, long term care

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Authors: Carla M. Machado, André A. Silva, Armando Bastos, Telmo G. Santos, J. Pamies Teixeira

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Advanced high-strength steels (AHSS) are increasingly being used in automotive components. The use of AHSS sheets plays an important role in reducing weight, as well as increasing the resistance to impact in vehicle components. However, the large-scale use of these sheets becomes more difficult due to the limitations during the forming process. Such limitations are due to the elastically driven change of shape of a metal sheet during unloading and following forming, known as the springback effect. As the magnitude of the springback tends to increase with the strength of the material, it is among the most worrisome problems in the use of AHSS steels. The prediction of strain hardening, especially under non-proportional loading conditions, is very limited due to the lack of constitutive models and mainly due to very limited experimental tests. It is very clear from the literature that in experimental terms there is not much work to evaluate deformation behavior under real conditions, which implies a very limited and scarce development of mathematical models for these conditions. The Bauschinger effect is also fundamental to the difference between kinematic and isotropic hardening models used to predict springback in sheet metal forming. It is of major importance to deepen the phenomenological knowledge of the mechanical and microstructural behavior of the materials, in order to be able to reproduce with high fidelity the behavior of extension of the materials by means of computational simulation. For this, a multi phenomenological analysis and characterization are necessary to understand the various aspects involved in plastic deformation, namely the stress-strain relations and also the variations of electrical conductivity and magnetic permeability associated with the metallurgical changes due to plastic deformation. Aiming a complete mechanical-microstructural characterization, uniaxial tensile tests involving successive cycles of loading and unloading were performed, as well as biaxial tests such as the Erichsen test. Also, nondestructive evaluation comprising eddy currents to verify microstructural changes due to plastic deformation and ultrasonic tests to evaluate the local variations of thickness were made. The material parameters for the stable yield function and the monotonic strain hardening were obtained using uniaxial tension tests in different material directions and balanced biaxial tests. Both the decrease of the modulus of elasticity and Bauschinger effect were determined through the load-unload tensile tests. By means of the eddy currents tests, it was possible to verify changes in the magnetic permeability of the material according to the different plastically deformed areas. The ultrasonic tests were an important aid to quantify the local plastic extension. With these data, it is possible to parameterize the different models of kinematic hardening to better approximate the results obtained by simulation with the experimental results, which are fundamental for the springback prediction of the stamped parts.

Keywords: advanced high strength steel, Bauschinger effect, sheet metal forming, springback

Procedia PDF Downloads 227

Authors: Maria Luisa Barcena De Arellano, Sofya Pozdniakova, Pavelas Karkacas, Anja Kuhl, Istvan Baczko, Yury Ladilov, Vera Regitz-Zagrosek

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Introduction: Aging is associated with deterioration of the physiological function, leading to systemic inflammation and mitochondrial dysfunction that promote the development of cardiovascular diseases. Sex differences in aging-related cardiovascular diseases have been postulated. However, their precise mechanisms remain unclear. In the current study, we aimed to investigate the sex difference in the age-related alteration in Sirt1-AMPK signaling and its relation to the mitochondrial biogenesis and inflammation. Methods: Male and female human non-disease lateral left ventricular wall tissue (young (17–40 years; n= 7 male and 7 female) and old (50–68 years; n= 9 male and 8 female)) were used. qRT-PCR, western blot and immunohistochemistry assays were performed for expression analyses of Sirt1, AMPK, pAMPK, ac-Ku70, TFAM, PGC-1α, Sirt3, SOD2 and catalase. CD68 was used as a marker for macrophages and the ratio of IL-12:IL10 (pro-inflammatory phenotype (high IL-12/low IL-10) and anti-inflammatory phenotype (low IL-12/high IL-10) was used to examine the inflammatory stage in the heart. Results: Sirt1 expression was significantly higher in young females compared to young males, whereas in aged hearts Sirt1 expression was significantly downregulated in females, but not in males. In line with the Sirt1 downregulation in aged females, acetylation of nuclear Ku70, a direct target of Sirt1, in aged female hearts was significantly elevated. The activity of AMPK was significantly decreased in aged individuals, however no sex differences in the AMPK expression or activity were found in young or old individuals. The expression of mitochondrial proteins TOM40, SOD2 and Sirt3 was significantly higher in young females compared to young males, while in aged female hearts SOD2 and TOM40 were downregulated. In addition, the expression of catalase, a key cytosolic and mitochondrial anti-oxidative enzyme was significantly higher in young females and this female sex benefit was lost in aged hearts. In addition, the number of cardiac macrophages was significantly increased in old female, but not in male hearts. Consistently, the pro-inflammatory shift in old females was further confirmed by differences in the IL12/IL10 ratio in young female cardiac tissue in a favour of the anti-inflammatory mediator IL-10 (ratio 1:4) compared to young males (ratio 1:1). The anti-inflammatory environment in the heart was lost in aged females (ratio 1:1). Conclusion: Aging leads to the significant downregulation of Sirt1 expression and elevated acetylation of Ku70 in female, but not in male hearts. Furthermore, a beneficial upregulation of mitochondrial and anti-oxidative proteins in young females is lost with aging. Moreover, the malfunctions in the expression of Sirt1 and mitochondrial proteins in aged female hearts is accompanied by a significant pro-inflammatory shift. The study provides a molecular basis for the increased incidence of cardiovascular diseases in old women.

Keywords: inflammation, mitochondrial dysfunction, aging, Sirt1-AMPK axis

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Authors: Nadine Maier, Martin Mensinger, Enea Tallushi

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In general, today, two types of launching bearings are used in the construction of large steel and steel concrete composite bridges. These are sliding rockers and systems with hydraulic bearings. The advantages and disadvantages of the respective systems are under discussion. During incremental launching, the center of the webs of the superstructure is not perfectly in line with the center of the launching bearings due to unavoidable tolerances, which may have an influence on the buckling behavior of the web plates. These imperfections are not considered in the current design against plate buckling, according to DIN EN 1993-1-5. It is therefore investigated whether the design rules have to take into account any eccentricities which occur during incremental launching and also if this depends on the respective launching bearing. Therefore, at the Technical University Munich, large-scale buckling tests were carried out on longitudinally stiffened plates under biaxial stresses with the two different types of launching bearings and eccentric load introduction. Based on the experimental results, a numerical model was validated. Currently, we are evaluating different parameters for both types of launching bearings, such as load introduction length, load eccentricity, the distance between longitudinal stiffeners, the position of the rotation point of the spherical bearing, which are used within the hydraulic bearings, web, and flange thickness and imperfections. The imperfection depends on the geometry of the buckling field and whether local or global buckling occurs. This and also the size of the meshing is taken into account in the numerical calculations of the parametric study. As a geometric imperfection, the scaled first buckling mode is applied. A bilinear material curve is used so that a GMNIA analysis is performed to determine the load capacity. Stresses and displacements are evaluated in different directions, and specific stress ratios are determined at the critical points of the plate at the time of the converging load step. To evaluate the load introduction of the transverse load, the transverse stress concentration is plotted on a defined longitudinal section on the web. In the same way, the rotation of the flange is evaluated in order to show the influence of the different degrees of freedom of the launching bearings under eccentric load introduction and to be able to make an assessment for the case, which is relevant in practice. The input and the output are automatized and depend on the given parameters. Thus we are able to adapt our model to different geometric dimensions and load conditions. The programming is done with the help of APDL and a Python code. This allows us to evaluate and compare more parameters faster. Input and output errors are also avoided. It is, therefore, possible to evaluate a large spectrum of parameters in a short time, which allows a practical evaluation of different parameters for buckling behavior. This paper presents the results of the tests as well as the validation and parameterization of the numerical model and shows the first influences on the buckling behavior under eccentric and multi-axial load introduction.

Keywords: buckling behavior, eccentric load introduction, incremental launching, large scale buckling tests, multi axial stress states, parametric numerical modelling

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Authors: Lina Psarra, Manogj Sundaresan, Purjeet Sutar

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In response to the global imperative for sustainable solutions, this article proposes the development of a comprehensive circularity index applicable to a wide range of products across various industries. The absence of a consensus on using a universal metric to assess circularity performance presents a significant challenge in prioritizing and effectively managing sustainable initiatives. This circularity index serves as a quantitative measure to evaluate the adherence of products, processes, and systems to the principles of a circular economy. Unlike traditional distinct metrics such as recycling rates or material efficiency, this index considers the entire lifecycle of a product in one single metric, also incorporating additional factors such as reusability, scarcity of materials, reparability, and recyclability. Through a systematic approach and by reviewing existing metrics and past methodologies, this work aims to address this gap by formulating a circularity index that can be applied to diverse product portfolio and assist in comparing the circularity of products on a scale of 0%-100%. Project objectives include developing a formula, designing and implementing a pilot tool based on the developed Product Circularity Index (PCI), evaluating the effectiveness of the formula and tool using real product data, and assessing the feasibility of integration into various sustainability initiatives. The research methodology involves an iterative process of comprehensive research, analysis, and refinement where key steps include defining circularity parameters, collecting relevant product data, applying the developed formula, and testing the tool in a pilot phase to gather insights and make necessary adjustments. Major findings of the study indicate that the PCI provides a robust framework for evaluating product circularity across various dimensions. The Excel-based pilot tool demonstrated high accuracy and reliability in measuring circularity, and the database proved instrumental in supporting comprehensive assessments. The PCI facilitated the identification of key areas for improvement, enabling more informed decision-making towards circularity and benchmarking across different products, essentially assisting towards better resource management. In conclusion, the development of the Product Circularity Index represents a significant advancement in global sustainability efforts. By providing a standardized metric, the PCI empowers companies and stakeholders to systematically assess product circularity, track progress, identify improvement areas, and make informed decisions about resource management. This project contributes to the broader discourse on sustainable development by offering a practical approach to enhance circularity within industrial systems, thus paving the way towards a more resilient and sustainable future.

Keywords: circular economy, circular metrics, circularity assessment, circularity tool, sustainable product design, product circularity index

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Authors: Sonia Bautista Carrascosa, Carlos Renedo Sanchez

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The effect of a rapid drawdown is a classical scenario to be considered in slope stability under submerged conditions. This situation arises when totally or partially submerged slopes experience a descent of the external water level and is a typical verification to be done in a dam engineering discipline, as reservoir water levels commonly fluctuate noticeably during seasons and due to operational reasons. Although the scenario is well known and predictable in general, site conditions can increase the complexity of its assessment and external factors are not always expected, can cause a reduction in the stability or even a failure in a slope under a rapid drawdown situation. The present paper describes and discusses the interaction between two different infrastructures, a dam and a highway, and the impact on the stability of a natural rock slope overlaid by the north abutment of a viaduct of the A-44 Highway due to the rapid drawdown of the Rules Dam, in the province of Granada (south of Spain). In the year 2011, with both infrastructures, the A-44 Highway and the Rules Dam already constructed, delivered and under operation, some movements start to be recorded in the approximation embankment and north abutment of the Guadalfeo Viaduct, included in the highway and developed to solve the crossing above the tail of the reservoir. The embankment and abutment were founded in a low-angle natural rock slope formed by grey graphic phyllites, distinctly weathered and intensely fractured, with pre-existing fault and weak planes. After the first filling of the reservoir, to a relative level of 243m, three consecutive drawdowns were recorded in the autumns 2010, 2011 and 2012, to relative levels of 234m, 232m and 225m. To understand the effect of these drawdowns in the weak rock mass strength and in its stability, a new geological model was developed, after reviewing all the available ground investigations, updating the geological mapping of the area and supplemented with an additional geotechnical and geophysical investigations survey. Together with all this information, rainfall and reservoir level evolution data have been reviewed in detail to incorporate into the monitoring interpretation. The analysis of the monitoring data and the new geological and geotechnical interpretation, supported by the use of limit equilibrium software Slide2, concludes that the movement follows the same direction as the schistosity of the phyllitic rock mass, coincident as well with the direction of the natural slope, indicating a deep-seated movement of the whole slope towards the reservoir. As part of these conclusions, the solutions considered to reinstate the highway infrastructure to the required FoS will be described, and the geomechanical characterization of these weak rocks discussed, together with the influence of water level variations, not only in the water pressure regime but in its geotechnical behavior, by the modification of the strength parameters and deformability.

Keywords: monitoring, rock slope stability, water drawdown, weak rock

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Authors: Zahra Mohajer, Afsaneh Soltani

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Doping is a major issue in competitive sports and is favored by vast groups of athletes. The feeling of being higher-ranking than others and gaining fame has caused many athletes to misuse drugs. The definition of doping is to use prohibited substances and/or methods that help physical or mental performances or both. Doping counts as the illegal use of chemical substances or drugs, excessive amounts of physiological substances to increase the performance at or out of competition or even the use of inappropriate medications to treat an injury to gain the ability to participate in a competition. The International Olympic Committee (IOC) and World Anti-Doping Agency (WADA) have forbidden these substances to ensure fair and equal competition and also the health of the competitors. As of 2004 WADA has published an international list of illegal substances used for doping, which is updated annually. In the process of the Genome Project scientists have gained the ability to treat numerous diseases by gene therapy, which may result in bodily performance increase and therefore a potential opportunity to misuse by some athletes. Gene doping is defined as the non-therapeutic direct and indirect genetic modifications using genetic materials that can improve the performances in sports events. Biosynthetic drugs are a form of indirect genetic engineering. The method can be performed in three ways such as injecting the DNA directly into the muscle, inserting the genetically engineered cells, or transferring the DNA using a virus as a vector. Erythropoietin is a hormone majorly released by the kidney and in small amounts by the liver. Its function is to stimulate the erythropoiesis and therefore the more production of red blood cells (RBC) which causes an increase in Hemoglobin (Hb). During this process, the oxygen delivery to muscles will increase, which will improve athletic performance and postpone exhaustion. There are ways to increase the oxygen transferred to muscles such as blood transfusion, stimulating the production of red blood cells by using Erythropoietin (EPO), and also using allosteric effectors of Hemoglobin. EPO can either be injected as a protein or can be inserted into the cells as the gene which encodes EPO. Adeno-associated viruses have been employed to deliver the EPO gene to the cells. Employing the genes that naturally exist in the human body such as the EPO gene can reduce the risk of detecting gene doping. The first research about blood doping was conducted in 1947. The study has shown that an increase in hematocrit (HCT) up to 55% following homologous transfusion makes it more unchallenging for the body to perform the exercise at the altitude. Thereafter athletes’ attraction to blood infusion escalated. Also, a study has demonstrated that by reinfusing their own blood 4 weeks after being drawn, three men have shown a rise in Hb level which improved the oxygen uptake, and a delay in exhaustion. The list of performance-enhancing drugs is published by WADA annually and includes the following drugs: anabolic agents, hormones, Beta-2 agonists, Beta-blockers, Diuretics, Stimulants, narcotics, cannabinoids, and corticosteroids.

Keywords: doping, PEDs, sports, WADA

Procedia PDF Downloads 106

Authors: Rahaba Marima, Clement Penny

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The Health-related quality of life (HRQoL) for HIV positive patients has improved since the introduction of the highly active antiretroviral treatment (HAART). However, in the present HAART era, HIV co-morbidities such as lung cancer, a non-AIDS (NAIDS) defining cancer have been documented to be on the rise. Under normal physiological conditions, cells grow, repair and proliferate through the cell-cycle as cellular homeostasis is important in the maintenance and proper regulation of tissues and organs. Contrarily, the deregulation of the cell-cycle is a hallmark of cancer, including lung cancer. The association between lung cancer and the use of HAART components such as Efavirenz (EFV) is poorly understood. This study aimed at elucidating the effects of EFV on the cell-cycle genes’ expression in lung cancer. For this purpose, the human cell-cycle gene array composed of 84 genes was evaluated on both normal lung fibroblasts (MRC-5) cells and adenocarcinoma (A549) lung cells, in response to 13µM EFV or 0.01% vehicle. The ±2 up or down fold change was used as a basis of target selection, with p < 0.05. Additionally, RT-qPCR was done to validate the gene array results. Next, In-silico bio-informatics tools, Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), Reactome, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Ingenuity Pathway Analysis (IPA) were used for gene/gene interaction studies as well as to map the molecular and biological pathways influenced by the identified targets. Interestingly, the DNA damage response (DDR) pathway genes such as p53, Ataxia telangiectasia mutated and Rad3 related (ATR), Growth arrest and DNA damage inducible alpha (GADD45A), HUS1 checkpoint homolog (HUS1) and Role of radiation (RAD) genes were shown to be upregulated following EFV treatment, as revealed by STRING analysis. Additionally, functional enrichment analysis by the KEGG pathway revealed that most of the differentially expressed gene targets function at the cell-cycle checkpoint such as p21, Aurora kinase B (AURKB) and Mitotic Arrest Deficient-Like 2 (MAD2L2). Core analysis by IPA revealed that p53 downstream targets such as survivin, Bcl2, and cyclin/cyclin dependent kinases (CDKs) complexes are down-regulated, following exposure to EFV. Furthermore, Reactome analysis showed a significant increase in cellular response to stress genes, DNA repair genes, and apoptosis genes, as observed in both normal and cancerous cells. These findings implicate the genotoxic effects of EFV on lung cells, provoking the DDR pathway. Notably, the constitutive expression of this pathway (DDR) often leads to uncontrolled cell proliferation and eventually tumourigenesis, which could be the attribute of HAART components’ (such as EFV) effect on human cancers. Targeting the cell-cycle and its regulation holds a promising therapeutic intervention to the potential HAART associated carcinogenesis, particularly lung cancer.

Keywords: cell-cycle, DNA damage response, Efavirenz, lung cancer

Procedia PDF Downloads 156

Authors: B. Neethu, Diptesh Das

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The present study investigates the performance of a semi-active controller using magneto-rheological dampers (MR) for seismic response reduction of a multi-span bridge. The application of structural control to the structures during earthquake excitation involves numerous challenges such as proper formulation and selection of the control strategy, mathematical modeling of the system, uncertainty in system parameters and noisy measurements. These problems, however, need to be tackled in order to design and develop controllers which will efficiently perform in such complex systems. A control algorithm, which can accommodate un-certainty and imprecision compared to all the other algorithms mentioned so far, due to its inherent robustness and ability to cope with the parameter uncertainties and imprecisions, is the sliding mode algorithm. A sliding mode control algorithm is adopted in the present study due to its inherent stability and distinguished robustness to system parameter variation and external disturbances. In general a semi-active control scheme using an MR damper requires two nested controllers: (i) an overall system controller, which derives the control force required to be applied to the structure and (ii) an MR damper voltage controller which determines the voltage required to be supplied to the damper in order to generate the desired control force. In the present study a sliding mode algorithm is used to determine the desired optimal force. The function of the voltage controller is to command the damper to produce the desired force. The clipped optimal algorithm is used to find the command voltage supplied to the MR damper which is regulated by a semi active control law based on sliding mode algorithm. The main objective of the study is to propose a robust semi active control which can effectively control the responses of the bridge under real earthquake ground motions. Lumped mass model of the bridge is developed and time history analysis is carried out by solving the governing equations of motion in the state space form. The effectiveness of MR dampers is studied by analytical simulations by subjecting the bridge to real earthquake records. In this regard, it may also be noted that the performance of controllers depends, to a great extent, on the characteristics of the input ground motions. Therefore, in order to study the robustness of the controller in the present study, the performance of the controllers have been investigated for fourteen different earthquake ground motion records. The earthquakes are chosen in such a way that all possible characteristic variations can be accommodated. Out of these fourteen earthquakes, seven are near-field and seven are far-field. Also, these earthquakes are divided into different frequency contents, viz, low-frequency, medium-frequency, and high-frequency earthquakes. The responses of the controlled bridge are compared with the responses of the corresponding uncontrolled bridge (i.e., the bridge without any control devices). The results of the numerical study show that the sliding mode based semi-active control strategy can substantially reduce the seismic responses of the bridge showing a stable and robust performance for all the earthquakes.

Keywords: bridge, semi active control, sliding mode control, MR damper

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Authors: Juliana Shimara Pires Ferrão, Letícia Palmeira Pinto, Francisco Palma Rennó, Francisco Javier Hernandez Blazquez

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The ruminant stomach is a complex and multi-chambered organ. Although the true stomach (abomasum) is fully differentiated and functional at birth, the same does not occur with the rumen chamber. At this moment, rumen papillae are small or nonexistent. The papillae only fully develop after weaning and during calf growth. Papillae development and ruminal epithelium specialization during the fetus growth and at birth must be two interdependent processes that will prepare the rumen to adapt to ruminant adult feeding. The microscopic study of rumen epithelium at these early phases of life is important to understand how this structure prepares the rumen to deal with the following weaning processes and its functional activation. Samples of ruminal mucosa of bovine fetuses (110- and 150 day-old) and newborn calves were collected (dorsal and ventral portions) and processed for light and electron microscopy and immunohistochemistry. The basal cell layer of the stratified pavimentous epithelium present in different ruminal portions of the fetuses was thicker than the same portions of newborn calves. The superficial and intermediate epithelial layers of 150 day-old fetuses were thicker than those found in the other 2 studied ages. At this age (150 days), dermal papillae begin to invade the intermediate epithelial layer which gradually disappears in newborn calves. At birth, the ruminal papillae project from the epithelial surface, probably by regression of the epithelial cells (transitory cells) surrounding the dermal papillae. The PCNA cell proliferation index (%) was calculated for all epithelial samples. Fetuses 150 day-old showed increased cell proliferation in basal cell layer (Dorsal Portion: 84.2%; Ventral Portion: 89.8%) compared to other ages studied. Newborn calves showed an intermediate index (Dorsal Portion: 65.1%; Ventral Portion: 48.9%), whereas 110 day-old fetuses had the lowest proliferation index (Dorsal Portion: 57.2%; Ventral Portion: 20.6%). Regarding the transitory epithelium, 110 day-old fetuses showed the lowest proliferation index (Dorsal Portion: 44.6%; Ventral Portion: 20.1%), 150 day-old fetuses showed an intermediate proliferation index (Dorsal Portion: 57.5%; Ventral Portion: 71.1%) and newborn calves presented a higher proliferation index (Dorsal Portion: 75.1%; Ventral Portion: 19.6%). Under TEM, the 110- and 150 day-old fetuses presented thicker and poorly organized basal cell layer, with large nuclei and dense cytoplasm. In newborn calves, the basal cell layer was more organized and with fewer layers, but typically similar in both regions of the rumen. For the transitory epithelium, fetuses displayed larger cells than those found in newborn calves with less electrondense cytoplasm than that found in the basal cells. The ruminal dorsal portion has an overall higher cell proliferation rate than the ventral portion. Thus we can infer that the dorsal portion may have a higher cell activity than the ventral portion during ruminal development. Moreover, the basal cell layer is thicker in the 110- and 150 day-old fetuses than in the newborn calves. The transitory epithelium, which is much reduced, at birth may have a structural support function of the developing dermal papillae. When it regresses or is sheared off, the papillae are “carved out” from the surrounding epithelial layer.

Keywords: bovine, calf, epithelium, fetus, hematoxylin-eosin, immunohistochemistry, TEM, Rumen

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Authors: Taner Izzet Acarer, Ece Ceylan Baba

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This paper examines green building certification systems and their current processes in comparison with anticipatory systems. Rapid growth of human population and depletion of natural resources are causing irreparable damage to urban and natural environment. In this context, the concept of ‘sustainable architecture’ has emerged in the 20th century so as to establish and maintain standards for livable urban spaces, to improve quality of urban life, and to preserve natural resources for future generations. The construction industry is responsible for a large part of the resource consumption and it is believed that the ‘green building’ designs that emerge in construction industry can reduce environmental problems and contribute to sustainable development around the world. A building must meet a specific set of criteria, set forth through various certification systems, in order to be eligible for designation as a green building. It is disputable whether methods used by green building certification systems today truly serve the purposes of creating a sustainable world. Accordingly, this study will investigate the sets of rating systems used by the most popular green building certification programs, including LEED (Leadership in Energy and Environmental Design), BREEAM (Building Research Establishment's Environmental Assessment Methods), DGNB (Deutsche Gesellschaft für Nachhaltiges Bauen System), in terms of ‘Anticipatory Systems’ in accordance with the certification processes and their goals, while discussing their contribution to architecture. The basic methodology of the study is as follows. Firstly analyzes of brief historical and literature review of green buildings and certificate systems will be stated. Secondly, processes of green building certificate systems will be disputed by the help of anticipatory systems. Anticipatory Systems is a set of systems designed to generate action-oriented projections and to forecast potential side effects using the most current data. Anticipatory Systems pull the future into the present and take action based on future predictions. Although they do not have a claim to see into the future, they can provide foresight data. When shaping the foresight data, Anticipatory Systems use feedforward instead of feedback, enabling them to forecast the system’s behavior and potential side effects by establishing a correlation between the system’s present/past behavior and projected results. This study indicates the goals and current status of LEED, BREEAM and DGNB rating systems that created by using the feedback technique will be examined and presented in a chart. In addition, by examining these rating systems with the anticipatory system that using the feedforward method, the negative influences of the potential side effects on the purpose and current status of the rating systems will be shown in another chart. By comparing the two obtained data, the findings will be shown that rating systems are used for different goals than the purposes they are aiming for. In conclusion, the side effects of green building certification systems will be stated by using anticipatory system models.

Keywords: anticipatory systems, BREEAM, certificate systems, DGNB, green buildings, LEED

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Authors: Robert Rorie, Lisa Fern

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The integration of Unmanned Aircraft Systems (UAS) into the National Airspace System (NAS) poses a variety of technical challenges to UAS developers and aviation regulators. In response to growing demand for access to civil airspace in the United States, the Federal Aviation Administration (FAA) has produced a roadmap identifying key areas requiring further research and development. One such technical challenge is the development of a ‘detect and avoid’ system (DAA; previously referred to as ‘sense and avoid’) to replace the ‘see and avoid’ requirement in manned aviation. The purpose of the DAA system is to support the pilot, situated at a ground control station (GCS) rather than in the cockpit of the aircraft, in maintaining ‘well clear’ of nearby aircraft through the use of GCS displays and alerts. In addition to its primary function of aiding the pilot in maintaining well clear, the DAA system must also safely interoperate with existing NAS systems and operations, such as the airspace management procedures of air traffic controllers (ATC) and collision avoidance (CA) systems currently in use by manned aircraft, namely the Traffic alert and Collision Avoidance System (TCAS) II. It is anticipated that many UAS architectures will integrate both a DAA system and a TCAS II. It is therefore necessary to explicitly study the integration of DAA and TCAS II alerting structures and maneuver guidance formats to ensure that pilots understand the appropriate type and urgency of their response to the various alerts. This paper presents a concept of interoperability for the two systems. The concept was developed with the goal of avoiding any negative impact on the performance level of TCAS II (understanding that TCAS II must largely be left as-is) while retaining a DAA system that still effectively enables pilots to maintain well clear, and, as a result, successfully reduces the frequency of collision hazards. The interoperability concept described in the paper focuses primarily on facilitating the transition from a late-stage DAA encounter (where a loss of well clear is imminent) to a TCAS II corrective Resolution Advisory (RA), which requires pilot compliance with the directive RA guidance (e.g., climb, descend) within five seconds of its issuance. The interoperability concept was presented to 10 participants (6 active UAS pilots and 4 active commercial pilots) in a medium-fidelity, human-in-the-loop simulation designed to stress different aspects of the DAA and TCAS II systems. Pilot response times, compliance rates and subjective assessments were recorded. Results indicated that pilots exhibited comprehension of, and appropriate prioritization within, the DAA-TCAS II combined alert structure. Pilots demonstrated a high rate of compliance with TCAS II RAs and were also seen to respond to corrective RAs within the five second requirement established for manned aircraft. The DAA system presented under test was also shown to be effective in supporting pilots’ ability to maintain well clear in the overwhelming majority of cases in which pilots had sufficient time to respond. The paper ends with a discussion of next steps for research on integrating UAS into civil airspace.

Keywords: detect and avoid, interoperability, traffic alert and collision avoidance system (TCAS II), unmanned aircraft systems

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Authors: Henry Lau, Dilupa Nakandala, Li Zhao

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In today’s business, it is well-recognized that risk is an important factor that needs to be taken into consideration before a decision is made. Studies indicate that both the number of risks faced by organizations and their potential consequences are growing. Supply chain risk management has become one of the major concerns for practitioners and researchers. Supply chain leaders and scholars are now focusing on the importance of managing supply chain risk. In order to meet the challenge of managing and mitigating supply chain risk (SCR), we must first identify the different dimensions of SCR and assess its relevant probability and severity. SCR has been classified in many different ways, and there are no consistently accepted dimensions of SCRs and several different classifications are reported in the literature. Basically, supply chain risks can be classified into two dimensions namely disruption risk and operational risk. Disruption risks are those caused by events such as bankruptcy, natural disasters and terrorist attack. Operational risks are related to supply and demand coordination and uncertainty, such as uncertain demand and uncertain supply. Disruption risks are rare but severe and hard to manage, while operational risk can be reduced through effective SCM activities. Other SCRs include supply risk, process risk, demand risk and technology risk. In fact, the disorganized classification of SCR has created confusion for SCR scholars. Moreover, practitioners need to identify and assess SCR. As such, it is important to have an overarching framework tying all these SCR dimensions together for two reasons. First, it helps researchers use these terms for communication of ideas based on the same concept. Second, a shared understanding of the SCR dimensions will support the researchers to focus on the more important research objective: operationalization of SCR, which is very important for assessing SCR. In general, fresh food supply chain is subject to certain level of risks, such as supply risk (low quality, delivery failure, hot weather etc.) and demand risk (season food imbalance, new competitors). Effective strategies to mitigate fresh food supply chain risk are required to enhance operations. Before implementing effective mitigation strategies, we need to identify the risk sources and evaluate the risk level. However, assessing the supply chain risk is not an easy matter, and existing research mainly use qualitative method, such as risk assessment matrix. To address the relevant issues, this paper aims to analyze the risk factor of the fresh food supply chain using an approach comprising both fuzzy logic and hierarchical holographic modeling techniques. This novel approach is able to take advantage the benefits of both of these well-known techniques and at the same time offset their drawbacks in certain aspects. In order to develop this integrated approach, substantial research work is needed to effectively combine these two techniques in a seamless way, To validate the proposed integrated approach, a case study in a fresh food supply chain company was conducted to verify the feasibility of its functionality in a real environment.

Keywords: fresh food supply chain, fuzzy logic, hierarchical holographic modelling, operationalization, supply chain risk

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Authors: E. Poupelloz, S. Gauffinet

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Ettringite Ca₆Al₂(SO₄)₃(OH)₁₂26H₂O is one of the major hydrates formed during cement hydration. Ettringite forms in Portland cement from the reaction between tricalcium aluminate Ca₃Al₂O₆ and calcium sulfate. Ettringite is also present in calcium sulfoaluminate cement in which it is the major hydrate, formed by the reaction between yeelimite Ca₄(AlO₂)₆SO₄ and calcium sulfate. About the formation of ettringite, numerous results are available in the literature even if some issues are still under discussion. However, almost all published work about ettringite was done on cementitious systems. Yet in cement, hydration reactions are very complex, the result of dissolution-precipitation processes and are submitted to various interactions. Understanding the formation process of a phase alone, here ettringite, is the first step to later understand the much more complex reactions happening in cement. This study is crucial for the comprehension of early cement hydration and physical behavior. Indeed formation of hydrates, in particular, ettringite, will have an influence on the rheological properties of the cement paste and on the need for admixtures. To make progress toward the understanding of existing phenomena, a specific study of nucleation and growth processes of ettringite was conducted. First ettringite nucleation was studied in ionic aqueous solutions, with controlled but different experimental conditions, as different supersaturation degrees (β), different pH or presence of exogenous ions. Through induction time measurements, interfacial ettringite crystals solution energies (γ) were determined. Growth of ettringite in supersaturated solutions was also studied through chain crystallization reactions. Specific BET surface area measurements and Scanning Electron Microscopy observations seemed to prove that growth process is favored over the nucleation process when ettringite crystals are initially present in a solution with a low supersaturation degree. The influence of stirring on ettringite formation was also investigated. Observation was made that intensity and nature of stirring have a high influence on the size of ettringite needles formed. Needle sizes vary from less than 10µm long depending on the stirring to almost 100µm long without any stirring. During all previously mentioned experiments, initially present ions are consumed to form ettringite in such a way that the supersaturation degree with regard to ettringite is decreasing over time. To avoid this phenomenon a device compensating the drop of ion concentrations by adding some more solutions, and therefore always have constant ionic concentrations, was used. This constant β recreates the conditions of the beginning of cement paste hydration, when the dissolution of solid reagents compensates the consumption of ions to form hydrates. This device allowed the determination of the ettringite precipitation rate as a function of the supersaturation degree β. Taking samples at different time during ettringite precipitation and doing BET measurements allowed the determination of the interfacial growth rate of ettringite in m²/s. This work will lead to a better understanding and control of ettringite formation alone and thus during cements hydration. This study will also ultimately define the impact of ettringite formation process on the rheology of cement pastes at early age, which is a crucial parameter from a practical point of view.

Keywords: cement hydration, ettringite, morphology of crystals, nucleation-growth process

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Authors: Sweta Agrawal, Sachin Chaugule, Gargi Rane, Shashank More, Madhavi Indap

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Angiogenesis and metastasis are two of the most important hallmarks of cancer. Hence, most of the cancer therapies nowadays are multi-targeted so as to reduce resistance and have better efficacy. As synthetic molecules arise with a burden of their toxicities and side-effects, more and more research is being focussed on exploiting the vast natural resources of drugs, in the form of plants and animals. Although, the idea of using marine organisms as a source of pharmaceuticals is not new, the pace at which marine drugs are being discovered, has definitely up surged! In the present study, we have assessed the anti-angiogenic and in vitro anti-metastatic activity of aqueous fraction from the extract of marine gastropod Euchelus asper. The soft body of Euchelus Asper was extracted with methanol and named EAME. Partition chromatography of EAME gave three fractions EAME I, II and III. Biochemical analysis revealed the presence of proteins in EAME III. Preliminary analysis had revealed the anti-angiogenic activity was exhibited by EAME III out of the three fractions. Hereafter, EAME III (concentration 25µg/ml-400µg/ml) was tested on chick chorioallantoic membrane (CAM) model for the detailed analysis of its potential anti-angiogenic effect. In vitro testing of the fraction (concentration 0.25µg/ml - 1µg/ml), involved cytotoxicity by SRB assay, cell cycle analysis by flow cytometry and anti-proliferative effect by scratch wound healing assay on A549 lung carcinoma cells. Apart from this, a portion of treated CAM as well as conditioned medium from treated A549 were subjected to gelatin zymography for assessment of matrix metalloproteinases MMP-2 and MMP-9 levels. Our results revealed that EAME III exhibited significant anti-angiogenic activity on CAM which was also supported by histological observations. During histological studies of CAM, it was found that EAME III caused reduction in angiogenesis by altering the extracellular matrix of the CAM membrane. In vitro analysis disclosed that EAME III exhibited moderate cytotoxic effect on A549 cells and its effect was not dose-dependent. The results of flow cytometry confirmed that EAME III caused cell cycle arrest in A549 cell line as almost all of the treated cells were found in G1 phase. Further, the migration and proliferation of A549 was significantly reduced by EAME III as observed from the scratch wound assay. Moreover, Gelatin zymography analysis revealed that EAME III caused suppression of MMP-2 in CAM membrane and reduced MMP-9 and MMP-2 expression in A549 cells. This verified that the anti-angiogenic and anti-metastatic effects of EAME III were correlated with the suppression of MMP-2 and -9. To conclude, EAME III shows dual anti-tumour action by reducing angiogenesis and exerting anti-metastatic effect on lung cancer cells, thus it has the potential to be used as an anti-cancer agent against lung carcinoma.

Keywords: angiogenesis, anti-cancer, marine drugs, matrix metalloproteinases

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Authors: Mariia A. Parfenenko, Ilya S. Dantsev, Sergei V. Bochenkov, Natalia V. Vinogradova, Olga S. Groznova, Victoria Yu. Voinova

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Introduction: Autism is the most common neurodevelopmental disorder. Autism is characterized by difficulties in social interaction and adherence to stereotypic behavioral patterns and frequently co-occurs with epilepsy, intellectual disabilities, connective tissue disorders, and other conditions. CHD8 codes for chromodomain-helicase-DNA-binding protein 8 - a chromatin remodeler that regulates cellular proliferation and neurodevelopment in embryogenesis. CHD8 is one of the genes most frequently involved in autism. Patients and methods: 2 unrelated male patients, P3 and P12, aged 3 and 12 years old, underwent whole genome sequencing, which determined that they both had different likely pathogenic variants, both previously undescribed in literature. Sanger sequencing later determined that P12 inherited the variant from his affected mother. Results: P3 and P12 presented with autism, a developmental delay, ataxia, sleep disorders, overgrowth, and macrocephaly, as well as other clinical features typically present in patients with causative variants in CHD8. The mother of P12 also has autistic traits, as well as ataxia, hypotonia, sleep disorders, and other symptoms. However, P3 and P12 also have different cardiac abnormalities. P3 had signs of a repolarization disorder: a flattened T wave in the III and aVF derivations and a negative T wave in the V1-V2 derivations. He also had structural valve anomalies with associated regurgitation, local contractility impairment of the left ventricular, and diastolic dysfunction of the right ventricle. Meanwhile, P12 had Wolff-Parkinson-White syndrome and underwent radiofrequency ablation at the age of 2 years. At the time of observation, P12 had mild sinus arrhythmia and an incomplete right bundle branch block, as well as arterial hypertension. Discussion: Cardiac abnormalities were not previously reported in patients with causative variants in CHD8. The underlying mechanism for the formation of those abnormalities is currently unknown. However, the two hypotheses are either a disordered interaction with CHD7 – another chromodomain remodeler known to be directly involved in the cardiophenotype of CHARGE syndrome – a rare condition characterized by coloboma, heart defects and growth abnormalities, or the disrupted functioning of CHD8 as an A-Kinase Anchoring Protein, which are known to modulate cardiac function. Conclusion: We observed 2 unrelated autistic males with likely pathogenic variants in CHD8 that presented with typical symptoms of CHD8-related neurodevelopmental disorder, as well as cardiac abnormalities. Cardiac abnormalities have, until now, been considered uncharacteristic for patients with causative variants in CHD8. Further accumulation of data, including experimental evidence of the involvement of CHD8 in heart formation, will elucidate the mechanism underlying the cardiophenotype of those patients. Acknowledgements: Molecular genetic testing of the patients was made possible by the Charity Fund for medical and social genetic aid projects «Life Genome.»

Keywords: autism spectrum disorders, chromodomain-helicase-DNA-binding protein 8, neurodevelopmental disorder, cardio phenotype

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Authors: Majid Manawer Alenezi, Gavin Lawrence, Hans-Peter Kubis

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Imagery training could be an important treatment for muscle function improvements in patients who are facing limitations in exercise training by pain or other adverse symptoms. However, recent studies are mostly limited to small muscle groups and are often contradictory. Moreover, a possible bilateral transfer effect of imagery training has not been examined. We, therefore, investigated the effectiveness of unilateral imagery training in comparison with exercise training on hip abductor muscle strength and EMG. Additionally, both limbs were assessed to investigate bilateral transfer effects. Healthy individuals took part in an imagery or exercise training intervention for two weeks and were assesses pre and post training. Participants (n=30), after randomization into an imagery and an exercise group, trained 5 times a week under supervision with additional self-performed training on the weekends. The training consisted of performing, or to imagine, 5 maximal isometric hip abductor contractions (= one set), repeating the set 7 times. All measurements and trainings were performed laying on the side on a dynamometer table. The imagery script combined kinesthetic and visual imagery with internal perspective for producing imagined maximal hip abduction contractions. The exercise group performed the same number of tasks but performing the maximal hip abductor contractions. Maximal hip abduction strength and EMG amplitudes were measured of right and left limbs pre- and post-training period. Additionally, handgrip strength and right shoulder abduction (Strength and EMG) were measured. Using mixed model ANOVA (strength measures) and Wilcoxen-tests (EMGs), data revealed a significant increase in hip abductor strength production in the imagery group on the trained right limb (~6%). However, this was not reported for the exercise group. Additionally, the left hip abduction strength (not used for training) did not show a main effect in strength, however, there was a significant interaction of group and time revealing that the strength increased in the imagery group while it remained constant in the exercise group. EMG recordings supported the strength findings showing significant elevation of EMG amplitudes after imagery training on right and left side, while the exercise training group did not show any changes. Moreover, measures of handgrip strength and shoulder abduction showed no effects over time and no interactions in both groups. Experiments showed that imagery training is a suitable method for effectively increasing functional parameters of larger limb muscles (strength and EMG) which were enhanced on both sides (trained and untrained) confirming a bilateral transfer effect. Indeed, exercise training did not reveal any increases in the parameters above omitting functional improvements. The healthy individuals tested might not easily achieve benefits from exercise training within the time tested. However, it is evident that imagery training is effective in increasing the central motor command towards the muscles and that the effect seems to be segmental (no increase in handgrip strength and shoulder abduction parameters) and affects both sides (trained and untrained). In conclusion, imagery training was effective in functional improvements in limb muscles and produced a bilateral transfer on strength and EMG measures.

Keywords: imagery, exercise, physiotherapy, motor imagery

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Authors: Rongrong Liu, Li Wang, Hui Xu, Jianpei Fang, Sixi Liu, Xiaolin Yin, Junbin Liang, Gaohui Yan, Yaoyun Li, Yali Zhou, Xinyu Li, Yue Li, Lei Shi, Yongrong Lai, Junjiu Huang, Xinhua Zhang

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Background: Beta-Thalassemia is caused by reduced (β+) or absent (β0) synthesis of the β-globin chains of hemoglobin. Transfusions and oral iron chelation therapy have improved the quality of life for patients with Transfusion-Dependent thalassemia (TDT). Recent advances in genome editing platforms of CRISPR-Cas9 have paved the way for induction of HbF by reactivating expression of γ-chain.Aims: We performed CRISPR-Cas9-mediated genome editing of hematopoietic stem cells to mutate HBG1/HBG2 promoter sequence, thereby representing a naturally occurring HPFH-liked mutation, producing RM-001. Here, we present an initial assessment of safety and efficacy of RM-001 in patients with TDT. Methods: Patients (6–35 y of age) with TDT receiving packed red blood cell (pRBC) transfusions of ≥100 mL/kg/y or ≥10 units/y in the previous 2 y were eligible. CD34+ cells were edited with CRISPR-Cas9 using a guide RNA specific for the binding site of BCL11A on the HBG1/2 promoter. Prior to RM-001 product infusion (day 0), patients received myeloablative conditioning with Busulfan from day-7 to day-4. Patients were monitored for AEs Hb expression.Results: Data cut as of 28 Feb 2024, 16 TDT patients have been treated with RM-001 and followed ≥3 months. 5 of these 16 patients had finished their 24 months follow up. Eleven patients have β0/β0 genotype and five patients have β0/β+ genotype. In addition to β-thalassemia, two patients had α- deletion with the genotype of --/αα. Efficacy:All patients received a single dose intravenous infusion of RM-001 cells. 5 of them had been followed 24 months or longer. All patients achieved transfusion-independent (TI, total Hb continued ≥ 9g/dL) (Figure1). Patients demonstrated sustained and clinically meaningful increases in HbF levels since 4 month post-RM-001 infusion (Figure.2). Total hemoglobin in all patients was stable at 10-12g/dL during the follow-up period. Safety:The adverse events observed after RM-001 infusion were consistent with those that are typical of Busulfan-based myeloablation. The allelic editing analysis at 6-month visit showed that the on-target allelic editing frequency in bone marrow cells was 73.44% (64.65% to 84.6%, n=13).Summary/Conclusion: This interim analysis, in which all the 19 patients age from 7.9 to 25yo met the success criteria for the trial with respect to transfusion independence, showed that autologous HBG1/2 promoter-modified CD34+ HSPCs gene therapy resulted in an adequate amount of HbF as early as 2 months after infusion led to near-normal hemoglobin levels, remained transfusion-free through the reported period without product related SAE. After RM-001 infusion, high levels of HbF proportion and on-target editing in bone marrow cells were maintained. Submitted on behalf of the RM-001 Investigators.

Keywords: thalassemian, genetherapy, CRISPR/Cas9, HbF

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