Search results for: postmenopausal period

Authors: Ahmad Saleem

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Ethereum is the second largest crypto currency in blockchain ecosystem. Along with standard transactions, it supports smart contracts and NFT’s. Current research trends are focused on analyzing the overall structure of the network its growth and behavior. Ethereum addresses are anonymous and can be created on fly. The nature of Ethereum network and addresses make it hard to predict their behavior. The activity period of an ethereum address is not much analyzed. Using machine learning we can make early prediction about the disposability of the address. In this paper we analyzed the lifetime of the addresses. We also identified and predicted the disposable addresses using machine learning models and compared the results.

Keywords: blockchain, Ethereum, cryptocurrency, prediction

Procedia PDF Downloads 97

Authors: Hamed Hedayatnia, Nathan Van Den Bossche

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Understanding the ways in which climate change accelerates or slows down the process of material deterioration is the first step towards assessing adaptive approaches for the conservation of historical heritage. Analysis of the climate change effects on the degradation risk assessment parameters like freeze-thaw cycles and wind erosion is also a key parameter when considering mitigating actions. Due to the vulnerability of cultural heritage to climate change, the impact of this phenomenon on material degradation criteria with the focus on brick masonry walls in Timurid heritage, located in Iran, was studied. The Timurids were the final great dynasty to emerge from the Central Asian steppe. Through their patronage, the eastern Islamic world in northwestern of Iran, especially in Mashhad and Herat, became a prominent cultural center. Goharshad Mosque is a mosque in Mashhad of the Razavi Khorasan Province, Iran. It was built by order of Empress Goharshad, the wife of Shah Rukh of the Timurid dynasty in 1418 CE. Choosing an appropriate regional climate model was the first step. The outputs of two different climate model: the 'ALARO-0' and 'REMO,' were analyzed to find out which model is more adopted to the area. For validating the quality of the models, a comparison between model data and observations was done in 4 different climate zones in Iran for a period of 30 years. The impacts of the projected climate change were evaluated until 2100. To determine the material specification of Timurid bricks, standard brick samples from a Timurid mosque were studied. Determination of water absorption coefficient, defining the diffusion properties and determination of real density, and total porosity tests were performed to characterize the specifications of brick masonry walls, which is needed for running HAM-simulations. Results from the analysis showed that the threatening factors in each climate zone are almost different, but the most effective factor around Iran is the extreme temperature increase and erosion. In the north-western region of Iran, one of the key factors is wind erosion. In the north, rainfall erosion and mold growth risk are the key factors. In the north-eastern part, in which our case study is located, the important parameter is wind erosion.

Keywords: brick, climate change, degradation criteria, heritage, Timurid period

Procedia PDF Downloads 119

Authors: M. V. Shivaani, P. K. Jain, Surendra S. Yadav

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Worldwide regulators, practitioners and researchers view risk-disclosure as one of the most important steps that will promote corporate accountability and transparency. Recognizing this growing significance of risk disclosures, the paper first develops a risk disclosure index. Covering 69 risk items/themes, this index is developed by employing thematic content analysis and encompasses three attributes of disclosure: namely, nature (qualitative or quantitative), time horizon (backward-looking or forward-looking) and tone (no impact, positive impact or negative impact). As the focus of study is on substantive rather than symbolic disclosure, content analysis has been carried out manually. The study is based on non-financial companies of Nifty500 index and covers a ten year period from April 1, 2005 to March 31, 2015, thus yielding 3,872 annual reports for analysis. The analysis reveals that (on an average) only about 14% of risk items (i.e. about 10 out 69 risk items studied) are being disclosed by Indian companies. Risk items that are frequently disclosed are mostly macroeconomic in nature and their disclosures tend to be qualitative, forward-looking and conveying both positive and negative aspects of the concerned risk. The second objective of the paper is to gauge the factors that affect the level of disclosures in annual reports. Given the panel nature of data, and possible endogeneity amongst variables, Diff-GMM regression has been applied. The results indicate that age and size of firms have a significant positive impact on disclosure quality, whereas growth rate does not have a significant impact. Further, post-recession period (2009-2015) has witnessed significant improvement in quality of disclosures. In terms of corporate governance variables, board size, board independence, CEO duality, presence of CRO and constitution of risk management committee appear to be significant factors in determining the quality of risk disclosures. It is noteworthy that the study contributes to literature by putting forth a variant to existing disclosure indices that not only captures the quantity but also the quality of disclosures (in terms of semantic attributes). Also, the study is a first of its kind attempt in a prominent emerging market i.e. India. Therefore, this study is expected to facilitate regulators in mandating and regulating risk disclosures and companies in their endeavor to reduce information asymmetry.

Keywords: risk disclosure, voluntary disclosures, corporate governance, Diff-GMM

Procedia PDF Downloads 162

Authors: Ö. Şenyiğit, A. Çolak

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It is of great importance for an architectural student to know the parameters through which he/she can conduct his/her design and makes his/her design effective in architectural education. Therefore; an empirical application study was carried out through the designing activity using the emulation model to support the design and design approaches of architectural students. During the investigation period, studies were done on the basic design elements and principles of the fall semester, and the emulation model, one of the designing methods that constitute the subject of the study, was fictionalized as three phased “recognition-interpretation-application”. As a result of the study, it was observed that when students were given a key method during the design process, their awareness increased and their aspects improved as well.

Keywords: basic design, design education, design methods, emulation

Procedia PDF Downloads 236

Authors: Meskure Pak, Nihal Buyukuslu

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During Ramadan Muslims refrain from eating and drinking from dawn to sunset. Transformation of the eating habits cause profound changes in body composition. This study was performed during Ramadan of June-July 2015 with the regular fasting healthy adults (15 women and 15 men). The participants who were not fasting the whole month, have chronic diseases, pregnant and lactated were excluded. All attendances were informed about study. Written informed consent was taken from the voluntary participants. The work was approved by the Ethics and Research Committee of Istanbul Medipol University, Turkey. A questionnaire was conducted to determine the nutritional status, demographic and anthropometric data at the beginning, in the middle and at the end of Ramadan. Statistical Package for Social Sciences version 18.0 (SPSS, Chicago, IL, USA) was used for analyses. The mean ages of women and men were 34.4±9.45 and 28.9±10.55 years respectively. The BMI values (kg/m2) were slightly increased in men (26.5±3.9 to 26.2±3.7) and decreased in women (22.5±3.5 to 23.3±4.5). However the differences in BMI values between genders were not significant. Waist circumferences (WC) (cm) decreased in both women (80.2±14.6 to 79.4±17.7) and men (98.9±8.4 to 95.2±11.0) through the Ramadan. Fat percentages of women (27.0±71) increased in the middle of Ramadan (28.4±7.8) and decreased at the end of Ramadan (27.8±8.3). The fat percentages of men (21.5±6.3) were not affected in the middle of Ramadan (21.5±6.4) however decreased at the end of Ramadan (20.8±6.2). The total change in fat mass from beginning to end of Ramadan was higher in women than in men. The daily energy intake was higher in men than in women during Ramadan. In the middle of Ramadan energy intake (kcal) was reached to the highest level (2057.8±693.1) and at the end of Ramadan it decreased to the beginning level (1656.7±553.2) for men. However, daily energy intake of women slightly decreased from the beginning (1410.0±359.7) to the end (1409.2±366.7) of Ramadan. The comparison of energy intake between men and women was significant in the middle of Ramadan (p < 0.05). Water consumptions for both groups were increased in Ramadan fasting period. In comparison with the beginning of Ramadan, daily carbohydrate and fat consumptions increased and the consumption of protein decreased for men and for women at the end of Ramadan. The gender comparison resulted in a significant increase for protein and carbohydrate consumption of men in the middle of Ramadan (p < 0.05). In the first two weeks, the daily energy intake, the consumption of carbohydrates and fats seemed to increase for both men and women. However the later days of Ramadan daily fat consumption decreased to the level of beginning consumption levels which may indicate the nutritional adaptation period. In spite of the consumption of protein sources such as meat, poultry and egg increased, the decrease in the total amount of protein consumed in Ramadan may be due to a decrease in the consumption of milk and dairy products. In conclusion, the nutritional habits and preferred foods changed during Ramadan as a result affected the body composition.

Keywords: body composition, fasting, nutritional status, Ramadan

Procedia PDF Downloads 224

Authors: Abdullah Al Mamoon, Niels E. Joergensen, Ataur Rahman, Hassan Qasem

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Intergovernmental Panel for Climate Change (IPCC) in its fourth Assessment Report AR4 predicts a more extreme climate towards the end of the century, which is likely to impact the design of engineering infrastructure projects with a long design life. A recent study in 2013 developed new design rainfall for Qatar, which provides an improved design basis of drainage infrastructure for the State of Qatar under the current climate. The current design standards in Qatar do not consider increased rainfall intensity caused by climate change. The focus of this paper is to update recently developed design rainfalls in Qatar under the changing climatic conditions based on IPCC's AR4 allowing a later revision to the proposed design standards, relevant for projects with a longer design life. The future climate has been investigated based on the climate models released by IPCC’s AR4 and A2 story line of emission scenarios (SRES) using a stationary approach. Annual maximum series (AMS) of predicted 24 hours rainfall data for both wet (NCAR-CCSM) scenario and dry (CSIRO-MK3.5) scenario for the Qatari grid points in the climate models have been extracted for three periods, current climate 2010-2039, medium term climate (2040-2069) and end of century climate (2070-2099). A homogeneous region of the Qatari grid points has been formed and L-Moments based regional frequency approach is adopted to derive design rainfalls. The results indicate no significant changes in the design rainfall on the short term 2040-2069, but significant changes are expected towards the end of the century (2070-2099). New design rainfalls have been developed taking into account climate change for 2070-2099 scenario and by averaging results from the two scenarios. IPCC’s AR4 predicts that the rainfall intensity for a 5-year return period rain with duration of 1 to 2 hours will increase by 11% in 2070-2099 compared to current climate. Similarly, the rainfall intensity for more extreme rainfall, with a return period of 100 years and duration of 1 to 2 hours will increase by 71% in 2070-2099 compared to current climate. Infrastructure with a design life exceeding 60 years should add safety factors taking the predicted effects from climate change into due consideration.

Keywords: climate change, design rainfalls, IDF, Qatar

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Authors: Getalem E. Haylia

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The Ribb dam is one of the irrigation projects in the Upper Blue Nile basin, Ethiopia, to irrigate the Fogera plain. Reservoir sedimentation is a major problem because it reduces the useful reservoir capacity by the accumulation of sediments coming from the watersheds. Estimates of sediment yield are needed for studies of reservoir sedimentation and planning of soil and water conservation measures. The objective of this study was to simulate the Ribb dam catchment sediment yield using SWAT model and to estimate Ribb reservoir effective life according to trap efficiency methods. The Ribb dam catchment is found in North Western part of Ethiopia highlands, and it belongs to the upper Blue Nile and Lake Tana basins. Soil and Water Assessment Tool (SWAT) was selected to simulate flow and sediment yield in the Ribb dam catchment. The model sensitivity, calibration, and validation analysis at Ambo Bahir site were performed with Sequential Uncertainty Fitting (SUFI-2). The flow data at this site was obtained by transforming the Lower Ribb gauge station (2002-2013) flow data using Area Ratio Method. The sediment load was derived based on the sediment concentration yield curve of Ambo site. Stream flow results showed that the Nash-Sutcliffe efficiency coefficient (NSE) was 0.81 and the coefficient of determination (R²) was 0.86 in calibration period (2004-2010) and, 0.74 and 0.77 in validation period (2011-2013), respectively. Using the same periods, the NS and R² for the sediment load calibration were 0.85 and 0.79 and, for the validation, it became 0.83 and 0.78, respectively. The simulated average daily flow rate and sediment yield generated from Ribb dam watershed were 3.38 m³/s and 1772.96 tons/km²/yr, respectively. The effective life of Ribb reservoir was estimated using the developed empirical methods of the Brune (1953), Churchill (1948) and Brown (1958) methods and found to be 30, 38 and 29 years respectively. To conclude, massive sediment comes from the steep slope agricultural areas, and approximately 98-100% of this incoming annual sediment loads have been trapped by the Ribb reservoir. In Ribb catchment, as well as reservoir systematic and thorough consideration of technical, social, environmental, and catchment managements and practices should be made to lengthen the useful life of Ribb reservoir.

Keywords: catchment, reservoir effective life, reservoir sedimentation, Ribb, sediment yield, SWAT model

Procedia PDF Downloads 187

Authors: Mimoza Canga, Irene Malagnino, Vergjini Mulo, Alketa Qafmolla, Vito Antonio Malagnino

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Background: Dental caries is the most common dental disease and pregnancy represents a special process of physical, hormonal and metabolic changes in pregnant women, which is accompanied by an imbalance in the oral cavity. Objective: The objective of this study is to evaluate caries reduction after dental visits, the scaling of teeth, fluoridated water, brushing of the teeth and using fluoride toothpaste before and during pregnancy. Materials and methods: This study was conducted in the time period March 2018- September 2021, the age range of the participants was: 18-41 years old. The sample taken under observation was composed of 84 pregnant women. The questionnaire included the demographic characteristics of the sample, such as age, women's education level was primary, secondary, and higher education. Based on women's education level, our analysis found that 25.9% of pregnant women had completed primary education, 35.2% of them had secondary education and 38.9% of pregnant women had higher education. The descriptive and analytical research analysis is formulated as a longitudinal study. Statistical analysis was performed using IBM SPSS Statistics 23.0. The significance level (α) was set at 0.05, whereas P-value and analysis of variance (ANOVA) were used to analyze the data. Results: In the present study, it was observed that there is a strong relationship between dental visits and the scaling of the teeth with the value of P˂ .0001. While the number of teeth with caries before pregnancy and fluoridated water have a P-value=0.002. If we compare the same factor with the number of teeth with dental caries during pregnancy, the correlation is P-value = 0.0001. The number of teeth with caries before pregnancy and carbohydrates consumption has a strong relation with P-value=0.05. According to the present research, the number of teeth with dental caries before pregnancy in relation to brushing the teeth has a P-value ˂ 0.05. Furthermore, in the actual research, it was established that using fluoride toothpaste doesn’t affect the number of teeth with caries before pregnancy with a P-value= .314. Conclusion: According to the results of the present study performed in Albania, it was found out that the periodical dental visits, scaling of the teeth, fluoridated water, brushing of the teeth influenced caries reduction before and during pregnancy. In comparison, the usage of fluoride toothpaste did not have any effect on dental caries reduction in the same time period. The recommendations are as follows: maintaining oral hygiene, using fluoridated water and brushing the teeth regularly. Healthcare providers should inform pregnant women about the importance of oral health and the implementation of measures to manage dental caries.

Keywords: brushing of the teeth, dental visits, dental scaling, fluoridated water, pregnancy

Procedia PDF Downloads 194

Authors: Asrat Agalu Abejew

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Background: Antimicrobial resistance (AMR) is a silent tsunami and one of the top global threats to health care and public health. It is one of the common agendas globally and in Ethiopia. Emerging AMR will be a double burden to Ethiopia, which is facing a series of problems from infectious disease morbidity and mortality. In Ethiopia, although there are attempts to document AMR in healthcare institutions, comprehensive and all-inclusive analysis is still lacking. Thus, this study is aimed to determine trends in AMR from 2016-2021. Methods: A retrospective analysis of secondary data recorded in the Amhara Public Health Institute (APHI) from 2016 to 2021 G.C was conducted. Blood, Urine, Stool, Swabs, Discharge, body effusions, and other Microbiological specimens were collected from each study participants, and Bacteria identification and Resistance tests were done using the standard microbiologic procedure. Data was extracted from excel in August 2022, Trends in AMR were analyzed, and the results were described. In addition, the chi-square (X2) test and binary logistic regression were used, and a P. value < 0.05 was used to determine a significant association. Results: During 6 years period, there were 25143 culture and susceptibility tests. Overall, 265 (46.2%) bacteria were resistant to 2-4 antibiotics, 253 (44.2%) to 5-7 antibiotics, and 56 (9.7%) to >=8 antibiotics. The gram-negative bacteria were 166 (43.9%), 155 (41.5%), and 55 (14.6%) resistant to 2-4, 5-7, and ≥8 antibiotics, respectively, whereas 99(50.8%), 96(49.2% and 1 (0.5%) of gram-positive bacteria were resistant to 2-4, 5-7 and ≥8 antibiotics respectively. K. pneumonia 3783 (15.67%) and E. coli 3199 (13.25%) were the most commonly isolated bacteria, and the overall prevalence of AMR was 2605 (59.9%), where K. pneumonia 743 (80.24%), E. cloacae 196 (74.81%), A. baumannii 213 (66.56%) being the most common resistant bacteria for antibiotics tested. Except for a slight decline during 2020 (6469 (25.4%)), the overall trend of AMR is rising from year to year, with a peak in 2019 (8480 (33.7%)) and in 2021 (7508 (29.9%). If left un-intervened, the trend in AMR will increase by 78% of variation from the study period, as explained by the differences in years (R2=0.7799). Ampicillin, Augmentin, ciprofloxacin, cotrimoxazole, tetracycline, and Tobramycin were almost resistant to common bacteria they were tested. Conclusion: AMR is linearly increasing during the last 6 years. If left as it is without appropriate intervention after 15 years (2030 E.C), AMR will increase by 338.7%. A growing number of multi-drug resistant bacteria is an alarm to awake policymakers and those who do have the concern to intervene before it is too late. This calls for a periodic, integrated, and continuous system to determine the prevalence of AMR in commonly used antibiotics.

Keywords: AMR, trend, pattern, MDR

Procedia PDF Downloads 76

Authors: Maryam Shayani Rad, Seyed Ahmad Mohajeri, Mohsen Mouhebati, Seyed Danial Mousavi

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High blood pressure is one of the most important and serious health-threatening because of no symptoms in most people, which can lead to sudden heart attack, heart failure, and stroke. Nowadays, herbal medicine is one of the best and safest strategies for treatment that have no adverse effects. Apium graveolens (celery) can be used as an alternative treatment for many health conditions such as hypertension. Natural compounds reduce blood pressure via different mechanisms in which Apium graveolens extract provides potent calcium channel blocking properties. A randomized, double-blind, placebo-controlled, cross-over clinical trial was done to evaluate the efficacy of formulated Apium graveolens extract with a maximum yield of 3-n-butylphthalide to reduce systolic and diastolic blood pressure in patients with hypertension. 54 hypertensive patients in the range of 20-68 years old were randomly assigned to the treatment group (26 cases) and the placebo control group (26 cases) and were crossed over after washout duration. The treatment group received at least 2 grams of formulated powder in hard capsules orally, before each meal, 2 times daily. The control group received 2 grams of placebo in hard capsules orally, exactly as the same as shape, time, and doses of treatment group. Treatment was administrated in 12 weeks with 4 weeks washout period at the middle of the study, meaning 4 weeks drug consumption for the treatment group, 4 weeks washout and 4 weeks placebo consumption, and vice versa for the placebo control group. The clinical assessment was done 4 times, including at the beginning and ending of the drug and placebo consumption period by 24-hour ambulatory blood pressure monitoring (ABPM) holter, which measured blood pressure every 15 minutes continuously. There was a statistically significant decrease in both systolic blood pressure (SBP) and diastolic blood pressure (DBP) at the end of drug duration compared to baseline. The changes after 4 weeks on average was about 12.34 mm Hg for the SBP (P < 0.005) and 7.83 mm Hg for the DBP (P < 0.005). The results from this clinical trial study showed this Apium graveolens extract formulation in the mentioned dosage had a significant effect on blood pressure-lowering for hypertensive patients.

Keywords: Apium graveolens extract, clinical trial, cross-over, hypertension

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Authors: Larisa Liamina, Vasily Lavrushin, Salvatore Inguaggiato

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This study presents and summarizes the results of researching the isotopic signature of helium in the deep fluid eastern part of the Southern slope of the Greater Caucasus and the Lesser Caucasus (Azerbaijan and Armenia) for the period from 2010 to 2016. The results of isotope ratios of 3He/4He in 59 samples of the gas phase of geothermal fluids and mud volcanoes are presented. New data have been obtained not only on the isotopic ratios of helium, but also neon and argon. The R/Ra ratio was analyzed along the Ankara-Sevan ophiolite structure. The patterns of lateral variations of the 3He/4He ratio of different geological structural elements of the studied region are revealed.

Keywords: isotopes helium, deep fluids, tectonic structures, Caucasus

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Authors: Yun Chen, David Penton, Fazlul Karim, Santosh Aryal, Shahriar Wahid, Peter Taylor, Susan M. Cuddy

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Droughts have severely affected Afghanistan over the last four decades, leading to critical food shortages where two-thirds of the country’s population are in a food crisis. Long years of conflict have lowered the country’s ability to deal with hazards such as drought, which can rapidly escalate into disasters. Understanding the spatial and temporal distribution of droughts is needed to be able to respond effectively to disasters and plan for future occurrences. This study used Standardized Precipitation Evapotranspiration Index (SPEI) at monthly, seasonal, and annual temporal scales to map the spatiotemporal change dynamics of drought characteristics (distribution, frequency, duration, and severity) in Afghanistan. SPEI indices were mapped for river basins, disaggregated into 189 sub-catchments, using monthly precipitation and potential evapotranspiration derived from temperature station observations from 1980 to 2017. The results show these multi-dimensional drought characteristics vary along different years, change among sub-catchments, and differ across temporal scales. During the 38 years, the driest decade and period are the 2000s and 1999–2022, respectively. The 2000–01 water year is the driest, with the whole country experiencing ‘severe’ to ‘extreme’ drought, more than 53% (87 sub-catchments) suffering the worst drought in history, and about 58% (94 sub-catchments) having ‘very frequent’ drought (7 to 8 months) or ‘extremely frequent’ drought (9 to 10 months). The estimated seasonal duration and severity present significant variations across the study area and throughout the study period. The nation also suffered from recurring droughts with varying length and intensity in 2004, 2006, 2008, and, most recently, 2011. There is a trend towards increasing drought with longer duration and higher severity extending all over sub-catchments from southeast to north and central regions. These datasets and maps help to fill the knowledge gap on detailed sub-catchment scale meteorological drought characteristics in Afghanistan. The study findings improve our understanding of the influences of climate change on drought dynamics and can guide catchment planning for reliable adaptation to and mitigation against future droughts.

Keywords: SPEI, precipitation, evapotranspiration, climate extremes

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Authors: Mercia I. Van Der Walt, Suzan Sayegh, Izzeldin E. L. J. Ibrahim, Mohamed G. Al-Kuwari, Manaf Kamil

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Background: Increased physical activity is associated with improvements in health conditions. Walking is recognized as an easy form of physical activity and a strategy used in health promotion. Step into Health (SIH), a national community program, was established in Qatar to support physical activity promotion through the monitoring of step counts. This study aims to assess the physical activity levels of the adult population in Qatar through a pedometer-based community program over a three-year-period. Methodology: This cross-sectional longitudinal study was conducted between from January 2013 and December 2015 based on daily step counts. A total of 15,947 adults (8,551 males and 7,396 females), from different nationalities enrolled in the program and aged 18 to 64, are included. The program involves free distribution of pedometers to members who voluntarily choose to register. It is also supported by a self-monitoring online account and linked to a web-database. All members are informed about the 10,000 steps/day target and automated emails as well as text messages are sent as reminders to upload data. Daily step counts were measured through the Omron HJ-324U pedometer (Omron Healthcare Co., Ltd., Japan). Analyses are done on the data extracted from the web-database. Results: Daily average step count for the overall community increased from 4,830 steps/day (2013) to 6,124 steps /day (2015). This increase was also observed within the three age categories (18–30), (31-45) and (>45) years. Average steps per day were found to be more among males compared with females in each of the aforementioned age groups. Moreover, males and females in the age group (>45 years) show the highest average step count with 7,010 steps/day and 5,564 steps/day respectively. The 21% increase in overall step count throughout the study period is associated with well-resourced program and ongoing impact in smaller communities such as workplaces and universities, a step in the right direction. However, the average step count of 6,124 steps/day in the third year is still classified as the low active category. Although the program showed an increase step count we found, 33% of the study population are low active, 35 % are sedentary with only 32% being active. Conclusion: This study indicates that the pedometer-based intervention was effective in increasing the daily physical activity of participants. However, alternative approaches need to be incorporated within the program to educate and encourage the community to meet the physical activity recommendations in relation to step count.

Keywords: pedometer, physical activity, Qatar, step count

Procedia PDF Downloads 250

Authors: Christine Y. Yeh, Brian D. Piening, Sarah M. Totten, Kimberly Kukurba, Wenyu Zhou, Kevin P. F. Contrepois, Gucci J. Gu, Sharon Pitteri, Michael Snyder

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Three million deaths worldwide are attributed to obesity. However, the biomolecular mechanisms that describe the link between adiposity and subsequent disease states are poorly understood. Insulin resistance characterizes approximately half of obese individuals and is a major cause of obesity-mediated diseases such as Type II diabetes, hypertension and other cardiovascular diseases. This study makes use of longitudinal quantitative and high-throughput multi-omics (genomics, epigenomics, transcriptomics, glycoproteomics etc.) methodologies on blood samples to develop multigenic and multi-analyte signatures associated with weight gain and insulin resistance. Participants of this study underwent a 30-day period of weight gain via excessive caloric intake followed by a 60-day period of restricted dieting and return to baseline weight. Blood samples were taken at three different time points per patient: baseline, peak-weight and post weight loss. Patients were characterized as either insulin resistant (IR) or insulin sensitive (IS) before having their samples processed via longitudinal multi-omic technologies. This comparative study revealed a wealth of biomolecular changes associated with weight gain after using methods in machine learning, clustering, network analysis etc. Pathways of interest included those involved in lipid remodeling, acute inflammatory response and glucose metabolism. Some of these biomolecules returned to baseline levels as the patient returned to normal weight whilst some remained elevated. IR patients exhibited key differences in inflammatory response regulation in comparison to IS patients at all time points. These signatures suggest differential metabolism and inflammatory pathways between IR and IS patients. Biomolecular differences associated with weight gain and insulin resistance were identified on various levels: in gene expression, epigenetic change, transcriptional regulation and glycosylation. This study was not only able to contribute to new biology that could be of use in preventing or predicting obesity-mediated diseases, but also matured novel biomedical informatics technologies to produce and process data on many comprehensive omics levels.

Keywords: insulin resistance, multi-omics, next generation sequencing, proteogenomics, type ii diabetes

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Authors: Jozef Mindas, Jana Skvareninova

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Wetlands are a main natural source of methane emissions, but they also represent the important biodiversity reservoirs in the landscape. There are about 26 thousands hectares of wetlands in Slovakia identified via the wetlands monitoring program. Created database of wetlands in Slovakia allows to analyze several ecological processes including also the methane emissions estimate. Based on the information from the database, the first estimate of the methane emissions from wetlands in Slovakia has been done. The IPCC methodology (Tier 1 approach) has been used with proposed emission factors for the ice-free period derived from the climatic data. The highest methane emissions of nearly 550 Gg are associated with the category of fens. Almost 11 Gg of methane is emitted from bogs, and emissions from flooded lands represent less than 8 Gg.

Keywords: bogs, methane emissions, Slovakia, wetlands

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Authors: Ila Shukla, Lubna Azmi, Shyam Sunder Gupta, C. V. Rao

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Treatments against Hepatitis-C virus (HCV) are already available, but the current high cost of such treatments limit them to wealthy patients only. Hence our current study is aimed at the rectification of HCV infection by using Lichen rangiferinus (LRE) extract in in vitro cultures. Anti-HCV activity of the given extract was evaluated using the virus grown in cell culture (HCVcc). Two control inhibitors, erlotinib and telaprevir, were systematically included in each experiment. At the end of the incubation period, we evaluated cell viability and viral replication. The LRE inhibited the growth of HCV in a dose dependent manner.

Keywords: Erlotinib, Hepatitis C, Lichen rangiferinus, Telaprevir

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Authors: Ahmed Hamza Yache

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The main purpose of this study is to estimate the distribution of shear forces in building structures with asymmetries in the plan submitted to seismic forces can cause, in this case, simultaneous deformations of translation and torsion. To this end, the distribution of shear forces is obtained by seismic forces calculated from the equivalent static method of the Algerian earthquake code RPA 99 (2003 version) and spectral modal analysis for an irregular building plan without kinks. Comparison of the results obtained by these two methods used to highlight the difference in terms of distributions of shear forces in such structures.

Keywords: structure, irregular, code, seismic, method, force, period

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Authors: Pradip Kumar Das

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India is a developing country and is also one of the most industrialized developing countries of the world. In post-independence period, industry has grown rapidly in India and with industrialization corporate sector in the country has been growing day after day. Nowadays, the investment is not limited to be shareholders alone, apart from the shareholders the common people of the society have also started investing in shares of the corporate sectors. Thus, the responsibilities of the corporate sectors have increased much. Corporate financial reporting refers to a system which provides valuable information to different types of users in the society for taking resourceful decisions with regards to investment policy, organization credit worthiness, profitability, liquidity, provision of taxation etc. The quality of information available to different users fosters the efficient allocation of resources which are very urgent for economic development of a country like India. It is the responsibility of the management of the corporate sector to convey reliable and authentic information with the help of generally accepted accounting principles. Corporate sectors which disclose information through annual reports should be sufficient enough for the purpose of bringing out the salient features relating to business performances and other activities. However, the disclosures practices of the corporate sectors though annual reports have undergone several major changes from time to time. Many a time, these vital changes are in the fashion of presenting information in the annual reports and addition of so many non-statutory disclosures of the company. Very often managements of the corporate sectors are blamed for concealing true picture which is not desirable at all. The corporate financial reporting practice which in the current period has gained a place of prime importance suffers from certain limitations and invites question from the public about its reliability. Thus, the wide gap created by management between the exhibited picture and the real picture sometimes attains to such extent that the purpose of the reporting practice loses its importance. The requirement of full and adequate disclosure of information including information relating to human resources in the annual report in free trade economy of India helps the prospective investors to select the best portfolio of their investments. This paper is a reflection of a modest attempt of the author to highlight the corporate reporting practices followed in India. A cursory glance of the conceptual study shows limitations along with reliability of the reporting practices and suggests measures to overcome the shortcomings of the financial reporting practices.

Keywords: corporate enterprise, cursory glance, portfolio, yawning gap

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Authors: Stamatis Zoras, Vasilis Evagelopoulos, Theodoros Staurakas

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The association between elevated air pollution levels and extreme climate conditions (temperature, particulate matter, ozone levels, etc.) and mental consequences has been, recently, the focus of significant number of studies. It varies depending on the time of the year it occurs either during the hot period or cold periods but, specifically, when extreme air pollution and weather events are observed, e.g. air pollution episodes and persistent heatwaves. It also varies spatially due to different effects of air quality and climate extremes to human health when considering metropolitan or rural areas. An air pollutant concentration and a climate extreme are taking a different form of impact if the focus area is countryside or in the urban environment. In the built environment the climate extreme effects are driven through the formed microclimate which must be studied more efficiently. Variables such as biological, age groups etc may be implicated by different environmental factors such as increased air pollution/noise levels and overheating of buildings in comparison to rural areas. Gridded air quality and climate variables derived from the land surface observations network of West Macedonia in Greece will be analysed against mortality data in a spatial format in the region of West Macedonia. Artificial intelligence (AI) tools will be used for data correction and prediction of health deterioration with climatic conditions and air pollution at local scale. This would reveal the built environment implications against the countryside. The air pollution and climatic data have been collected from meteorological stations and span the period from 2000 to 2009. These will be projected against the mortality rates data in daily, monthly, seasonal and annual grids. The grids will be operated as AI-based warning models for decision makers in order to map the health conditions in rural and urban areas to ensure improved awareness of the healthcare system by taken into account the predicted changing climate conditions. Gridded data of climate conditions, air quality levels against mortality rates will be presented by AI-analysed gridded indicators of the implicated variables. An Al-based gridded warning platform at local scales is then developed for future system awareness platform for regional level.

Keywords: air quality, artificial inteligence, climatic conditions, mortality

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Authors: Adhinarayanan Venkatasubramanian

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For design of high speed digital circuit wave pipeline is the best approach this can be operated at higher operating frequencies by adjusting clock periods and skews so as latch the o/p of combinational logic circuit at the stable period. In this paper, there are two methods are proposed in automation task one is BIST (Built in self test) and second method is Reconfigurable technique. For the above two approaches dedicated AND gate (multiplier) by applying wave pipeline technique. BIST approach is implemented by Xilinx Spartan-II device. In reconfigurable technique done by ASIC. From the results, wave pipeline circuits are faster than nonpipeline circuit and area, power dissipation are reduced by reconfigurable technique.

Keywords: SOC, wave-pipelining, FPGA, self-testing, reconfigurable, ASIC

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Authors: Abraham Dayan

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Remediation of soil containing volatile contaminants is often conducted by vapor extraction (SVE) technique. The operation is based on injection of air at ambient temperatures with or without thermal soil warming. Thermal enhancements of soil vapor extraction (TESVE) processes are usually conducted by soil heating, sometimes assisted by added steam injections. The current study addresses a technique which has not received adequate attention and is based on using exclusively hot air as an alternative to the common TESVE practices. To demonstrate the merit of the hot air TESVE technique, a sandy soil containing contaminated water is studied. Numerical and analytical tools were used to evaluate the rate of decontamination processes for various geometries and operating conditions. The governing equations are based on the Darcy law and are applied to an expanding compressible flow within a sandy soil. The equations were solved to determine the minimal time required for complete soil remediation. An approximate closed form solution was developed based on the assumption of local thermodynamic equilibrium and on a linearized representation of temperature dependence of the vapor to air density ratio. The solution is general in nature and offers insight into the governing processes of the soil remediation operation, where self-similar temperature profiles under certain conditions may exist, and the noticeable role of the contaminants evaporation and recondensation processes in affecting the remediation time. Based on analyses of the hot air TESVE technique, it is shown that it is sufficient to heat the air during a certain period of the decontamination process without compromising its full advantage, and thereby, entailing a minimization of the air-heating-energy requirements. This in effect is achieved by regeneration, leaving the energy stored in the soil during the early period of the remediation process to heat the subsequently injected ambient air, which infiltrates through it for the decontamination of the remaining untreated soil zone. The characteristic time required to complete SVE operations are calculated as a function of, both, the injected air temperature and humidity. For a specific set of conditions, it is demonstrated that elevating the injected air temperature by 20oC, the hot air injection technique reduces the soil remediation time by 50%, while requiring 30% of additional energy consumption. Those evaluations clearly unveil the advantage of the hot air SVE process, which for insignificant cost of added air heating energy, the substantial cost expenditures for manpower and equipment utilization are reduced.

Keywords: Porous Media, Soil Decontamination, Hot Air, Vapor Extraction

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Authors: Yuko Ishiwaka, Tomohiro Yoshida, Tadateru Itoh

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Human makes preparation called readiness potential unconsciously (RP) before awareness of their own decision. For example, when recognizing a button and pressing the button, the RP peaks are observed 200 ms before the initiation of the movement. It has been known that the preparatory movements are acquired before actual movements, but it has not been still well understood how humans can obtain the RP during their growth. On the proposition of why the brain must respond earlier, we assume that humans have to adopt the dangerous environment to survive and then obtain the behavior to cover the various time lags distributed in the body. Without RP, humans cannot take action quickly to avoid dangerous situations. In taking action, the brain makes decisions, and signals are transmitted through the Spinal Cord to the muscles to the body moves according to the laws of physics. Our research focuses on the time lag of the neuron signal transmitting from a brain to muscle via a spinal cord. This time lag is one of the essential factors for readiness potential. We propose a firing pattern controller model of a motor nerve system considered innervation and jitter, which produces time lag. In our simulation, we adopt innervation and jitter in our proposed muscle-skeleton model, because these two factors can create infinitesimal time lag. Q10 Hodgkin Huxley model to calculate action potentials is also adopted because the refractory period produces a more significant time lag for continuous firing. Keeping constant power of muscle requires cooperation firing of motor neurons because a refractory period stifles the continuous firing of a neuron. One more factor in producing time lag is slow or fast-twitch. The Expanded Hill Type model is adopted to calculate power and time lag. We will simulate our model of muscle skeleton model by controlling the firing pattern and discuss the relationship between the time lag of physics and neurons. For our discussion, we analyze the time lag with our simulation for knee bending. The law of inertia caused the most influential time lag. The next most crucial time lag was the time to generate the action potential induced by innervation and jitter. In our simulation, the time lag at the beginning of the knee movement is 202ms to 203.5ms. It means that readiness potential should be prepared more than 200ms before decision making.

Keywords: firing patterns, innervation, jitter, motor nerve system, readiness potential

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Authors: Fatiha Boudjema, Samia Boudergua, Abdallah Elhirtsi Nour El Houda, Ahmed Mbarek Kaouther

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The main objective of our work is to prepare and characterize a moisturizing lip balm based on natural ingredients such as waxes, vegetable oils, and shea butter. First, the vegetable and essential oils were extracted, and then lip balm was prepared. The extracted oils and the lip balm were submitted to many tests in order to guarantee their quality and effectiveness. These tests show that our balm has a shear thinning behavior with a melting point of 58 °C and that it spreads easily on the skin without showing an allergic reaction. The balm showed a moisturising effect and stability over the two-month period at storage room temperature condition.

Keywords: lip balm, natural products, rheological study, antioxydant activity

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Authors: Sebastian Wójtowicz, Anna Mosiołek, Anna Słupik, Zbigniew Wroński, Dariusz Białoszewski

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Introduction: In whole-body vibration (WBV) high-frequency mechanical stimuli is generated by a vibration plate and is transferred through bone, muscle and connective tissues to the whole body. The research has shown that the implementation of a vibration plate training over a long period of time leads to improvement of neuromuscular facilitation, especially in afferent neural pathways, which are responsible for the conduction of vibration and proprioceptive stimuli, muscle function, balance, and proprioception. The vibration stimulus is suggested to briefly inhibit the conduction of afferent signals from proprioceptors and may hinder the maintenance of body balance. The purpose of this study was to evaluate the result of a single set of exercises connected with whole-body vibration on the proprioception. Material and Methods: The study enrolled 60 people aged 19-24 years. These individuals were divided into a test group (group A) and a control group (group B). Both groups consisted of 30 persons and performed the same set of exercises on a vibration plate. The following vibration parameters: frequency of 20Hz and amplitude of 3mm, were used in the group A. The vibration plate was turned off while the control group did their exercises. All participants performed six dynamic 30-seconds-long exercises with a 60-second resting period between them. Large muscle groups of the trunk, pelvis, and lower limbs were involved while taking the exercises. The results were measured before and immediately after the exercises. The proprioception of lower limbs was measured in a closed kinematic chain using a Humac 360®. Participants were instructed to perform three squats with biofeedback in a defined range of motion. Then they did three squats without biofeedback which were measured. The final result was the average of three measurements. Statistical analysis was performed using Statistica 10.0 PL software. Results: There were no significant differences between the groups, both before and after the exercise (p > 0.05). The proprioception did not change in both the group A and the group B. Conclusions: 1. Deterioration in proprioception was not observed immediately after the vibration stimulus. This suggests that vibration-induced blockage of proprioceptive stimuli conduction can only have a short-lasting effect occurring only in the presence of the vibration stimulus. 2. Short-term use of vibration seems to be safe for patients with proprioceptive impairment due to the fact that the treatment does not decrease proprioception. 3. There is a need for supplementing the results with evaluation of proprioception while vibration stimuli are being applied. Moreover, the effects of vibration parameters used in the exercises should be evaluated.

Keywords: joint position sense, proprioception, squat, whole body vibration

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Authors: Mohd Shazad, K. K. Gupta

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Vector borne diseases are a serious global concern. Aedes aegypti, the primary vector for viruses that cause dengue fever, dengue haemorrhagic fever, chikungunya and yellow fever is widespread over large areas of the tropics and subtropics. In last decade, diseases transmitted by Aedes aegypti are of serious concern. In past decade, number of cases of dengue fever, dengue hemorrhagic fever, and chikungunya has increased multifold. Present research work focused on impact of ethanol extract of Ocimum sanctum on dengue vector Aedes aegypti. 0-24 hr. old fourth instar larvae of lab-bred population of Aedes aegypti were exposed to ethanol leaf extract of Ocimum with concentrations ranging from 50 ppm to 400 ppm. Survival and development and the treated larvae and reproductive behaviour of the adults emerged from the treated larvae was evaluated. Our results indicated larvicidal potential of the leaf ethanol extract. The influence of the extract was dose dependent. 77.2% mortality was observed in the larvae exposed to 400 ppm for 24 hr. Treatment at lower concentrations revealed delayed toxicity. The larvae survived after treatment showed severe developmental anomalies. Consequently, there was the significant increase in duration of fourth instar larva. The L4 treated with 400-ppm extract moulted after 4.6 days; this was in sharp contrast to control where the larval period of the fourth instar lasts three days. The treated fourth instar larvae in many cases transformed into larva-pupa intermediates with the combination of larva, pupa characters. The larva-pupa intermediates had reduced life span and failed to moult successfully. The adults emerged from the larvae treated with lower doses had reduced reproductive potential. The females exhibited longer preoviposition period, reduced oviposition rate, abnormal oviposition behaviour and decreased fertility. Our studies indicated the possibility of the presence of JH mimic or JH analogue in the leaf ethanol extract of Ocimum. The present research work explored the potentials of Ocimum sanctum, also known as the queen of herbs, in integrated vector management programme of Aedes aegypti, which is a serious threat to human health.

Keywords: Aedes aegypti, development, mortality, Ocimum sanctum reproduction

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Authors: Gaurav Gupta, Jitendra Mahakud

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This study focuses on the significance of internal financing constraints on the determination of corporate fixed investments in the case of Indian manufacturing companies. Financing constraints companies which have less internal fund or retained earnings face more transaction and borrowing costs due to imperfections in the capital market. The period of study is 1999-2000 to 2013-2014 and we consider 618 manufacturing companies for which the continuous data is available throughout the study period. The data is collected from PROWESS data base maintained by Centre for Monitoring Indian Economy Pvt. Ltd. Panel data methods like fixed effect and random effect methods are used for the analysis. The Likelihood Ratio test, Lagrange Multiplier test, and Hausman test results conclude the suitability of the fixed effect model for the estimation. The cash flow and liquidity of the company have been used as the proxies for the internal financial constraints. In accordance with various theories of corporate investments, we consider other firm specific variable like firm age, firm size, profitability, sales and leverage as the control variables in the model. From the econometric analysis, we find internal cash flow and liquidity have the significant and positive impact on the corporate investments. The variables like cost of capital, sales growth and growth opportunities are found to be significantly determining the corporate investments in India, which is consistent with the neoclassical, accelerator and Tobin’s q theory of corporate investment. To check the robustness of results, we divided the sample on the basis of cash flow and liquidity. Firms having cash flow greater than zero are put under one group, and firms with cash flow less than zero are put under another group. Also, the firms are divided on the basis of liquidity following the same approach. We find that the results are robust to both types of companies having positive and negative cash flow and liquidity. The results for other variables are also in the same line as we find for the whole sample. These findings confirm that internal financing constraints play a significant role for determination of corporate investment in India. The findings of this study have the implications for the corporate managers to focus on the projects having higher expected cash inflows to avoid the financing constraints. Apart from that, they should also maintain adequate liquidity to minimize the external financing costs.

Keywords: cash flow, corporate investment, financing constraints, panel data method

Procedia PDF Downloads 241

Authors: W. Hajuthman, R. Warner, S. Rahman, M. Abraham, H. Helliwell, D. Bodiwala

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Context: Prostate cancer is a prevalent cancer in males in Europe and the US, with diagnosis primarily relying on PSA testing, mpMRI, and subsequent biopsies. However, this diagnostic strategy may lead to complications for patients. Research Aim: The aim of this study is to assess compliance with trust guidelines for antibiotic prophylaxis in patients undergoing transperineal template biopsies of the prostate and evaluate the rate of post-procedure complications. Methodology: This study is conducted retrospectively over an 8-month period. Data collection includes patient demographics, compliance with trust guidelines, associated risk factors, and post-procedure complications such as infection, haematuria, and urinary retention. Findings: The audit includes 100 patients with a median age of 66.11. The compliance with pre-procedure antibiotics was 98%, while compliance with antibiotic prophylaxis recommended by trust guidelines was 68%. Among the patients, 3% developed post-procedure sepsis, with 2 requiring admission for intravenous antibiotics. No evident risk factors were identified in these cases. Additionally, post-procedure urinary retention occurred in 3% of patients and post-procedure haematuria in 2%. Theoretical Importance: This study highlights the increasing use of transperineal template biopsies across UK centres and suggests that having a standardized protocol and compliance with guidelines can reduce confusion, ensure appropriate administration of antibiotics, and mitigate post-procedure complications. Data Collection and Analysis Procedures: Data for this study is collected retrospectively, involving the extraction and analysis of relevant information from patient records over the specified 8-month period. Question Addressed: This study addresses the following research questions: (1) What is the compliance rate with trust guidelines for antibiotic prophylaxis in transperineal template biopsies of the prostate? (2) What is the rate of post-procedure complications, such as infection, haematuria, and urinary retention? Conclusion: Transperineal template biopsies are becoming increasingly prevalent in the UK. Implementing a standardized protocol and ensuring compliance with guidelines can reduce confusion, ensure proper administration of antibiotics, and potentially minimize post-procedure complications. Additionally, considering that studies show no difference in outcomes when prophylactic antibiotics are not used, the reminder to follow trust guidelines may prompt a re-evaluation of antibiotic prescribing practices.

Keywords: prostate, transperineal template biopsies of prostate, antibiotics, complications, microbiology, guidelines

Procedia PDF Downloads 79

Authors: Y. S. Yusoff, G. Streftaris, H. R Waters

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Death within 30 days is an important factor to be looked into, as there is a significant risk of deaths immediately following or soon after, Myocardial Infarction (MI) or stroke. In this paper, we will model the deaths within 30 days following a Myocardial Infarction (MI) or stroke in the UK. We will see how the probabilities of sudden deaths from MI or stroke have changed over the period 1981-2000. We will model the sudden deaths using a Generalized Linear Model (GLM), fitted using the R statistical package, under a Binomial distribution for the number of sudden deaths. We parameterize our model using the extensive and detailed data from the Framingham Heart Study, adjusted to match UK rates. The results show that there is a reduction for the sudden deaths following a MI over time but no significant improvement for sudden deaths following a stroke.

Keywords: sudden deaths, myocardial infarction, stroke, ischemic heart disease

Procedia PDF Downloads 286

Authors: Franklin Chu Buh, Irene Ule Ngole Sumbele, Andrew I. R. Maas, Mathieu Motah, Jogi V. Pattisapu, Eric Youm, Basil Kum Meh, Firas H. Kobeissy, Kevin W. Wang, Peter J. A. Hutchinson, Germain Sotoing Taiwe

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Introduction: Studying TBI characteristics and their relation to outcomes can identify initiatives to improve TBI prevention and care. The objective of this study was to define the features and outcomes of TBI patients seen over a 1-year period in a level-I trauma center in Cameroon. Methods: Data on demographics, causes, injury mechanisms, clinical aspects, and discharge status were prospectively collected over a period of 12 months. The Glasgow Outcome Scale-Extended (GOSE) and the Quality of Life Questionnaire after Brain Injury (QoLIBRI) were used to evaluate outcomes 6-months after TBI. Categorical variables were described as frequencies and percentages. Comparisons between 2 categorical variables were done using Pearson's Chi-square test or Fisher's exact test. Results: A total of 160 TBI patients participated in the study. The age group 15-45 years (78%; 125) was most represented. Males were more affected (90%; 144). Low educational level was recorded in 122 (76%) cases. Road traffic incidents (RTI) were the main cause of TBI (85%), with professional bike riders being frequently involved (27%, 43/160). Assaults (7.5%) and falls (2.5%) represent the second and third most common causes of TBI in Cameroon, respectively. Only 15 patients were transported to the hospital by ambulance, and 14 of these were from a referring hospital. CT-imaging was performed in 78% (125/160) of cases intracranial traumatic abnormality was identified in 77/125 (64%) cases. Financial constraints were the main reason for not performing a CT scan on 35 patients. A total of 46 (33%) patients were discharged against medical advice (DAMA) due to financial constraints. Mortality was 14% (22/160) but disproportionately high in patients with severe TBI (46%). DAMA had poor outcomes with QoLIBRI. Only 4 patients received post-injury physiotherapy services. Conclusion: TBI in Cameroon mainly results from RTIs and commonly affects young adult males, and low educational or socioeconomic status and commercial bike riding appear to be predisposing factors. Lack of pre-hospital care, financial constraints limiting both CT-scanning and medical care, and lack of acute physiotherapy services likely influenced care and outcomes adversely.

Keywords: characteristics, traumatic brain injury, outcome, disparities in care, prospective study

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Authors: Narin Ozturk, Xiao-Mei Li, Sylvie Giachetti, Francis Levi, Alper Okyar

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P-glycoprotein (P-gp, MDR1, ABCB1) is a transmembrane protein acting as an ATP-dependent efflux pump and functions as a biological barrier by extruding drugs and xenobiotics out of cells in healthy tissues especially in intestines, liver and brain as well as in tumor cells. The circadian timing system controls a variety of biological functions in mammals including xenobiotic metabolism and detoxification, proliferation and cell cycle events, and may affect pharmacokinetics, toxicity and efficacy of drugs. Selective mTOR (mammalian target of rapamycin) inhibitor everolimus is an immunosuppressant and anticancer drug that is active against many cancers, and its pharmacokinetics depend on P-gp. The aim of this study was to investigate the dosing time-dependent toxicity of everolimus with respect to the intestinal P-gp expression rhythms in mdr1a::Luc mice using Real Time-Biolumicorder (RT-BIO) System. Mdr1a::Luc male mice were synchronized with 12 h of Light and 12 h of Dark (LD12:12, with Zeitgeber Time 0 – ZT0 – corresponding Light onset). After 1-week baseline recordings, everolimus (5 mg/kg/day x 14 days) was administered orally at ZT1-resting period- and ZT13-activity period- to mdr1a::Luc mice singly housed in an innovative monitoring device, Real Time-Biolumicorder units which let us monitor real-time and long-term gene expression in freely moving mice. D-luciferin (1.5 mg/mL) was dissolved in drinking water. Mouse intestinal mdr1a::Luc oscillation profile reflecting P-gp gene expression and locomotor activity pattern were recorded every minute with the photomultiplier tube and infrared sensor respectively. General behavior and clinical signs were monitored, and body weight was measured every day as an index of toxicity. Drug-induced body weight change was expressed relative to body weight on the initial treatment day. Statistical significance of differences between groups was validated with ANOVA. Circadian rhythms were validated with Cosinor Analysis. Everolimus toxicity changed as a function of drug timing, which was least following dosing at ZT13, near the onset of the activity span in male mice. Mean body weight loss was nearly twice as large in mice treated with 5 mg/kg everolimus at ZT1 as compared to ZT13 (8.9% vs. 5.4%; ANOVA, p < 0.001). Based on the body weight loss and clinical signs upon everolimus treatment, tolerability for the drug was best following dosing at ZT13. Both rest-activity and mdr1a::Luc expression displayed stable 24-h periodic rhythms before everolimus and in both vehicle-treated controls. Real-time bioluminescence pattern of mdr1a revealed a circadian rhythm with a 24-h period with an acrophase at ZT16 (Cosinor, p < 0.001). Mdr1a expression remained rhythmic in everolimus-treated mice, whereas down-regulation was observed in P-gp expression in 2 of 4 mice. The study identified the circadian pattern of intestinal P-gp expression with an unprecedented precision. The circadian timing depending on the P-gp expression rhythms may play a crucial role in the tolerability/toxicity of everolimus. The circadian changes in mdr1a genes deserve further studies regarding their relevance for in vitro and in vivo chronotolerance of mdr1a-transported anticancer drugs. Chronotherapy with P-gp-effluxed anticancer drugs could then be applied according to their rhythmic patterns in host and tumor to jointly maximize treatment efficacy and minimize toxicity.

Keywords: circadian rhythm, chronotoxicity, everolimus, mdr1a::Luc mice, p-glycoprotein

Procedia PDF Downloads 342