Search results for: population PK
4940 Simulation Studies of High-Intensity, Nanosecond Pulsed Electric Fields Induced Dynamic Membrane Electroporation
Authors: Jiahui Song
Abstract:
The application of an electric field can cause poration at cell membranes. This includes the outer plasma membrane, as well as the membranes of intracellular organelles. In order to analyze and predict such electroporation effects, it becomes necessary to first evaluate the electric fields and the transmembrane voltages. This information can then be used to assess changes in the pore formation energy that finally yields the pore distributions and their radii based on the Smolchowski equation. The dynamic pore model can be achieved by including a dynamic aspect and a dependence on the pore population density into the pore formation energy equation. These changes make the pore formation energy E(r) self-adjusting in response to pore formation without causing uncontrolled growth and expansion. By using dynamic membrane tension, membrane electroporation in response to a 180kV/cm trapezoidal pulse with a 10 ns on time and 1.5 ns rise- and fall-times is discussed. Poration is predicted to occur at times beyond the peak at around 9.2 ns. Modeling also yields time-dependent distributions of the membrane pore population after multiple pulses. It shows that the pore distribution shifts to larger values of the radius with multiple pulsing. Molecular dynamics (MD) simulations are also carried out for a fixed field of 0.5 V/nm to demonstrate nanopore formation from a microscopic point of view. The result shows that the pore is predicted to be about 0.9 nm in diameter and somewhat narrower at the central point.Keywords: high-intensity, nanosecond, dynamics, electroporation
Procedia PDF Downloads 1594939 Study on the Relationship between the Urban Geography and Urban Agglomeration to the Effects of Carbon Emissions
Authors: Peng-Shao Chen, Yen-Jong Chen
Abstract:
In recent years, global warming, the dramatic change in energy prices and the exhaustion of natural resources illustrated that energy-related topic cannot be ignored. Despite the relationship between the cities and CO₂ emissions has been extensively studied in recent years, little attention has been paid to differences in the geographical location of the city. However, the geographical climate has a great impact on lifestyle from city to city, such as the type of buildings, the major industry of the city, etc. Therefore, the paper instigates empirically the effects of kinds of urban factors and CO₂ emissions with consideration of the different geographic, climatic zones which cities are located. Using the regression model and a dataset of urban agglomeration in East Asia cities with over one million population, including 2005, 2010, and 2015 three years, the findings suggest that the impact of urban factors on CO₂ emissions vary with the latitude of the cities. Surprisingly, all kinds of urban factors, including the urban population, the share of GDP in service industry, per capita income, and others, have different level of impact on the cities locate in the tropical climate zone and temperate climate zone. The results of the study analyze the impact of different urban factors on CO₂ emissions in urban area with different geographical climate zones. These findings will be helpful for the formulation of relevant policies for urban planners and policy makers in different regions.Keywords: carbon emissions, urban agglomeration, urban factor, urban geography
Procedia PDF Downloads 2674938 Intensity Analysis to Link Changes in Land-Use Pattern in the Abuakwa North and South Municipalities, Ghana, from 1986 to 2017
Authors: Isaac Kwaku Adu, Jacob Doku Tetteh, John Joseph Puthenkalam, Kwabena Effah Antwi
Abstract:
The continuous increase in population implies increase in food demand. There is, therefore, the need to increase agricultural production and other forest products to ensure food security and economic development. This paper employs the three-level intensity analysis to assess the total change of land-use in two-time intervals (1986-2002 and 2002-2017), the net change and swap as well as gross gains and losses in the two intervals. The results revealed that the overall change in the 31-year period was greater in the second period (2002-2017). Agriculture and forest categories lost in the first period while the other land class gained. However, in the second period agriculture and built-up increased greatly while forest, water bodies and thick bushes/shrubland experienced loss. An assessment revealed a reduction of forest in both periods but was greater in the second period and expansion of agricultural land was recorded as population increases. The pixels gaining built-up targeted agricultural land in both intervals, it also targeted thick bushes/shrubland and waterbody in the second period only. Built-up avoided forest in both intervals as well as waterbody and thick bushes/shrubland. To help in developing the best land-use strategies/policies, a further validation of the social factors is necessary.Keywords: agricultural land, forest, Ghana, land-use, intensity analysis, remote sensing
Procedia PDF Downloads 1534937 Contents for the Maintenance and Troubleshooting of Anti-lock Braking System for Automobile Craftsmen in Nigeria
Authors: Arah Abubakar Saidu, Audu Rufai, Abdulkadir Mohammed, Ibrahim Yakubu Umar, Idris Abubakar Mohammed
Abstract:
The study determined the contents for the maintenance and troubleshooting of an anti-lock braking system for automobile craftsmen in Nigeria. Two research questions were raised and answered and two null hypotheses were formulated and tested at a .05 level of significance. The study adopted a descriptive survey research design. The study was conducted in Federal Capital Territory (FCT), Abuja, Kaduna, Kano, Lagos and Plateau States, Nigeria. The targeted population for the study was 99 consisting of all 43 non-teaching Subject Matter Experts (SMEs). The study utilized the whole population of the study. The instruments used for data collection were Anti-lock Braking System Maintenance and Troubleshooting Contents Questionnaire (ABSMTQ). Mean was used to analyze data that answered research questions and Z-test was used in testing the null hypotheses. Findings revealed, among others, that 81 items as content for the maintenance of ABS and 61 items as content for troubleshooting ABS for automobile craftsmen in Nigeria. Based on the findings of the study, the recommended, among others, that the National Board for Technical Education should include the contents for the maintenance and troubleshooting ABS in Motor Vehicle Mechanic Works curriculum used for training automobile craftsmen through the process of curriculum review in order to equip them with the competencies in troubleshooting and maintenance of ABS.Keywords: anti-lock braking system, maintenance, troubleshooting, automobile craftsmen
Procedia PDF Downloads 884936 Urban Metis Women’s Identity and Experiences with Health Services in Toronto, Ontario
Authors: Renee Monchalin
Abstract:
Métis peoples, while comprising over a third of the total Indigenous population in Canada, experience major gaps in health services that accommodate their cultural identities. This is problematic given Métis peoples experience severe disparities in health determinants and outcomes compared to the non-Indigenous Canadian population. At the same time, Métis are unlikely to engage in health services that do not value their cultural identities, often utilizing mainstream options. Given these contexts, this research aims to fill the culturally-safe health care gap for Métis peoples in Canada. It does this by engaging 56 urban Métis women who participated in a longitudinal cohort study, Our Health Counts (OHC) Toronto. Traditionally, Métis women were central to the health and well-being of their communities. However, due to decades of colonial legislation and forced land displacement, female narratives have been silenced, and Métis identities have been fractured. This has resulted in having direct implications on Métis people’s current health and access to health services. Solutions to filling the Métis health service gap may lie in the all too often unacknowledged or missing voices of Métis women. Through a conversational method, this research will explore urban Métis women’s perspectives on identity and their experiences with health services in Toronto. The goal of this research is to learn from urban Métis women on steps towards filling the health service gap. This research is currently in the data collection stage. Preliminary findings from the conversations will be disseminated. Policy recommendations for health service providers will be provided to better accommodate Métis people.Keywords: indigenous health, Metis health, urban, health service access, identity
Procedia PDF Downloads 2164935 HIV and AIDS in Kosovo, Stigma Persist!
Authors: Luljeta Gashi, Naser Ramadani, Zana Deva, Dafina Gexha-Bunjaku
Abstract:
The official HIV/AIDS data in Kosovo are based on HIV case reporting from health-care services, the blood transfusion system and Voluntary Counselling and Testing centres. Between 1986 and 2014, are reported 95 HIV and AIDS cases, of which 49 were AIDS, 46 HIV and 40 deaths. The majority (69%) of cases were men, age group 25 to 34 (37%) and route of transmission is: heterosexual (90%), MSM (7%), vertical transmission (2%) and IDU (1%). Based on existing data and the UNAIDS classification system, Kosovo is currently still categorised as having a low-level HIV epidemic. Even though with a low HIV prevalence, Kosovo faces a number of threatening factors, including increased number of drug users, a stigmatized and discriminated MSM community, high percentage of youth among general population (57% of the population under the age of 25), with changing social norms and especially the sexual ones. Methods: Data collection was done using self administered structured questionnaires amongst 249 high school students. Data were analysed using the Statistical Package for Social Sciences (SPSS). Results: The findings revealed that 68% of students know that HIV transmission can be reduced by having sex with only one uninfected partner who has no other partners, 94% know that the risk of getting HIV can be reduced by using a condom every time they have sex, 68% know that a person cannot get HIV from mosquito bites, 81% know that they cannot get HIV by sharing food with someone who is infected and 46% know that a healthy looking person can have HIV. Conclusions: Seventy one percent of high school students correctly identify ways of preventing the sexual transmission of HIV and who reject the major misconceptions about HIV transmission. The findings of the study indicate a need for more health education and promotion.Keywords: Kosovo, KPAR, HIV, high school
Procedia PDF Downloads 4784934 Impact of a Locally-Prepared Fermented Alcoholic Beverage from Jaggery on the Gut Bacterial Profile of the Tea-Tribal Populations of Assam, India
Authors: Rupamoni Thakur, Madhusmita Dehingia, Narayan C. Talukdar, Mojibur R. Khan
Abstract:
The human gut is an extremely active fermentation site and is inhabited by diverse bacterial species. Consumption of alcoholic beverages has been shown to substantially modulate the human gut bacterial profile (GBP) of an individual. Assam, a major north-eastern state of India, is home to a number of tribal populations of which the tea-tribes form a major community. These tea-tribal communities are known to prepare and consume a locally-prepared alcoholic beverage from fermented jaggery, whose chemical composition is unknown. In this study, we demonstrate the effect of daily intake of the locally-prepared alcoholic beverage on the GBP of the tea-tribal communities and correlate it with the changes in the biochemical biomarkers of the population. The fecal bacterial diversity of 40 drinkers and 35 non-drinking healthy individuals were analyzed by polymerase chain reaction (PCR)–denaturing gradient gel electrophoresis (DGGE). The results suggested that the GBP was significantly modulated in the fermented-beverage consuming subjects. Significant difference was also observed in the serum biochemical parameters such as triglyceride, total cholesterol and the liver marker enzymes (ASAT/ALAT and GGT). Further studies to identify the GBP of drinkers vs non-drinkers through Next-generation Sequencing (NGS) analysis and to correlate the changes with the biochemical biomarkers of the population is underway.Keywords: alcoholic beverage, gut bacterial profile, PCR-DGGE analysis, tea-tribes of India
Procedia PDF Downloads 3274933 Heuristic Approaches for Injury Reductions by Reduced Car Use in Urban Areas
Authors: Stig H. Jørgensen, Trond Nordfjærn, Øyvind Teige Hedenstrøm, Torbjørn Rundmo
Abstract:
The aim of the paper is to estimate and forecast road traffic injuries in the coming 10-15 years given new targets in urban transport policy and shifts of mode of transport, including injury cross-effects of mode changes. The paper discusses possibilities and limitations in measuring and quantifying possible injury reductions. Injury data (killed and seriously injured road users) from six urban areas in Norway from 1998-2012 (N= 4709 casualties) form the basis for estimates of changing injury patterns. For the coming period calculation of number of injuries and injury rates by type of road user (categories of motorized versus non-motorized) by sex, age and type of road are made. A prognosticated population increase (25 %) in total population within 2025 in the six urban areas will curb the proceeded fall in injury figures. However, policy strategies and measures geared towards a stronger modal shift from use of private vehicles to safer public transport (bus, train) will modify this effect. On the other side will door to door transport (pedestrians on their way to/from public transport nodes) imply a higher exposure for pedestrians (bikers) converting from private vehicle use (including fall accidents not registered as traffic accidents). The overall effect is the sum of these modal shifts in the increasing urban population and in addition diminishing return to the majority of road safety countermeasures has also to be taken into account. The paper demonstrates how uncertainties in the various estimates (prediction factors) on increasing injuries as well as decreasing injury figures may partly offset each other. The paper discusses road safety policy and welfare consequences of transport mode shift, including reduced use of private vehicles, and further environmental impacts. In this regard, safety and environmental issues will as a rule concur. However pursuing environmental goals (e.g. improved air quality, reduced co2 emissions) encouraging more biking may generate more biking injuries. The study was given financial grants from the Norwegian Research Council’s Transport Safety Program.Keywords: road injuries, forecasting, reduced private care use, urban, Norway
Procedia PDF Downloads 2374932 Monitoring Land Cover/Land Use Change in Rupandehi District by Optimising Remotely Sensed Image
Authors: Hritik Bhattarai
Abstract:
Land use and land cover play a crucial role in preserving and managing Earth's natural resources. Various factors, such as economic, demographic, social, cultural, technological, and environmental processes, contribute to changes in land use and land cover (LULC). Rupandehi District is significantly influenced by a combination of driving forces, including its geographical location, rapid population growth, economic opportunities, globalization, tourism activities, and political events. Urbanization and urban growth in the region have been occurring in an unplanned manner, with internal migration and natural population growth being the primary contributors. Internal migration, particularly from neighboring districts in the higher and lower Himalayan regions, has been high, leading to increased population growth and density. This study utilizes geospatial technology, specifically geographic information system (GIS), to analyze and illustrate the land cover and land use changes in the Rupandehi district for the years 2009 and 2019, using freely available Landsat images. The identified land cover categories include built-up area, cropland, Das-Gaja, forest, grassland, other woodland, riverbed, and water. The statistical analysis of the data over the 10-year period (2009-2019) reveals significant percentage changes in LULC. Notably, Das-Gaja shows a minimal change of 99.9%, while water and forest exhibit increases of 34.5% and 98.6%, respectively. Riverbed and built-up areas experience changes of 95.3% and 39.6%, respectively. Cropland and grassland, however, show concerning decreases of 102.6% and 140.0%, respectively. Other woodland also indicates a change of 50.6%. The most noteworthy trends are the substantial increase in water areas and built-up areas, leading to the degradation of agricultural and open spaces. This emphasizes the urgent need for effective urban planning activities to ensure the development of a sustainable city. While Das-Gaja seems unaffected, the decreasing trends in cropland and grassland, accompanied by the increasing built-up areas, are unsatisfactory. It is imperative for relevant authorities to be aware of these trends and implement proactive measures for sustainable urban development.Keywords: land use and land cover, geospatial, urbanization, geographic information system, sustainable urban development
Procedia PDF Downloads 604931 Evaluation of Urban Land Development Direction in Kabul City, Afghanistan
Authors: Ahmad Sharif Ahmadi, Yoshitaka Kajita
Abstract:
Kabul, the capital and largest city in Afghanistan has been experiencing a massive population expansion and fast economic development in last decade, in which urban land has increasingly expanded and formed a high informal development territory in the city. This paper investigates the urban land development direction based on the integrated urbanization trends in Kabul city since the last and the fastest ever urban land growth period (1999-2008), which is parallel with the establishment of the new government in Afghanistan. Considering the existing challenges in terms of informal settlements, squatter settlements, the population expansion of the city, and fast economic development, as well as the huge influx of returning refugees from neighboring countries, and the sprawl direction of urbanization of the Kabul city urban fringes, this research focuses on the possible urban land development direction and trends for the city. The paper studies the feasible future land development direction of Kabul city in the northern part called Shamali basin, in which district 17 is the gateway for future development. The area has much developable area including eight districts of Kabul province, and the vast area of Parwan and Kapisa provinces. The northern area of the Kabul city generally has favorable conditions for further urbanization from the city. It is a large and relatively flat area of area in the northern part of Kabul city, with ample water resources available from the Panjshir basin as a base principle of land development direction in the area.Keywords: Kabul city, land development trends, urban land development, urbanization
Procedia PDF Downloads 2814930 An Investigation into the Effect of Broken Homes on Students Academic Performance
Authors: Hafsat Mustapha Hanga
Abstract:
The purpose of the this study was to investigate the effect of broken home on students' academic performance. Therefore, it focused on academic performance and Parental care of the student from and intact home from a cognitive motivational perceptive. The broken and intact home and also to find out if they differ in parental care this is done by using 376 subjects out of the population of 21,378. The sample was obtained using stratified random sampling techniques as the population contained sub-groups the study design was ex-post facto. The data was collected using 3 kind of instruments. To test the first and second hypotheses. Junior secondary school placement examination result was obtained to test the academic performance of the boys fron broken home and boys from and boys from intact home and then girl from broken home and girls from intact home.T-Test was used in the analysis of first and second hypotheses. For the third hypotheses two different kind of questionnaires were developed, the first was used to identify student that are from broken home while the second was for testing parental care between the subject. Chi-square was used to analyze the third hypotheses. Alkh the three 3 hypotheses were tested and rejected and were all in favor of student from intact home. The study found that there was a significant difference in the academic performance of the boys from brokeb and boys from intact home. When boys from intact home better then those boys from broken home. It also reveals that a student from a intact from intact home receives good parental care, love and concern than those from broken home.on the strength of these findings the need to establish an institution which will help those parent who have parenting problems was stressed and also the need to foster. Home school partnership was also stressed and advocate.Keywords: broken homes, academic performance, parental care, foster
Procedia PDF Downloads 4634929 The Relationship between Infill Development Indicators and Quality of Life in Urban Neighborhoods
Authors: S. Mohammad Reza Khatibi
Abstract:
Statistics on urbanization in Iran and around the world show that urbanization rate and urban population had had an increasing growth and, during five decades, this trend shows the fact that growth will still continue for a long time. Therefore, instead of an irregular horizontal city development and growth, a sustainable development is achievable by filling the existing city fabric, organizing the density and changing the use of incompatible old or urban buildings. One approach is the infill development. Infill development is the development of vacant land or wasteland abandoned within built areas or where there already exist facilities and equipment. Simply put, infill development is the use of empty spaces or those lacking intra-city use for city development. Additionally, fulfillment of social justice and creating a safe, secure and desirable atmosphere for citizens to live and stay active along with acquiring equal life opportunities, are among the goals of vision plan of Iran in conflict with which, certain environments have been created by city neighborhoods having physical, social, economic, etc. problems. Accordingly, in order to meet the extensive need of many cities for openness to growing population, this paper aims to investigate the relationship between infill development indicators and life quality in urban neighborhoods, using descriptive-analytical research method. Findings show that infill development indicators in three physical, social and economic categories can be adapted with quality components of urban environments, especially urban neighborhoods, and related guidelines can be offered.Keywords: infill development, life quality, urban neighborhoods, indicator
Procedia PDF Downloads 3594928 Empirical Modeling and Spatial Analysis of Heat-Related Morbidity in Maricopa County, Arizona
Authors: Chuyuan Wang, Nayan Khare, Lily Villa, Patricia Solis, Elizabeth A. Wentz
Abstract:
Maricopa County, Arizona, has a semi-arid hot desert climate that is one of the hottest regions in the United States. The exacerbated urban heat island (UHI) effect caused by rapid urbanization has made the urban area even hotter than the rural surroundings. The Phoenix metropolitan area experiences extremely high temperatures in the summer from June to September that can reach the daily highest of 120 °F (48.9 °C). Morbidity and mortality due to the environmental heat is, therefore, a significant public health issue in Maricopa County, especially because it is largely preventable. Public records from the Maricopa County Department of Public Health (MCDPH) revealed that between 2012 and 2016, there were 10,825 incidents of heat-related morbidity incidents, 267 outdoor environmental heat deaths, and 173 indoor heat-related deaths. A lot of research has examined heat-related death and its contributing factors around the world, but little has been done regarding heat-related morbidity issues, especially for regions that are naturally hot in the summer. The objective of this study is to examine the demographic, socio-economic, housing, and environmental factors that contribute to heat-related morbidity in Maricopa County. We obtained heat-related morbidity data between 2012 and 2016 at census tract level from MCDPH. Demographic, socio-economic, and housing variables were derived using 2012-2016 American Community Survey 5-year estimate from the U.S. Census. Remotely sensed Landsat 7 ETM+ and Landsat 8 OLI satellite images and Level-1 products were acquired for all the summer months (June to September) from 2012 and 2016. The National Land Cover Database (NLCD) 2016 percent tree canopy and percent developed imperviousness data were obtained from the U.S. Geological Survey (USGS). We used ordinary least squares (OLS) regression analysis to examine the empirical relationship between all the independent variables and heat-related morbidity rate. Results showed that higher morbidity rates are found in census tracts with higher values in population aged 65 and older, population under poverty, disability, no vehicle ownership, white non-Hispanic, population with less than high school degree, land surface temperature, and surface reflectance, but lower values in normalized difference vegetation index (NDVI) and housing occupancy. The regression model can be used to explain up to 59.4% of total variation of heat-related morbidity in Maricopa County. The multiscale geographically weighted regression (MGWR) technique was then used to examine the spatially varying relationships between heat-related morbidity rate and all the significant independent variables. The R-squared value of the MGWR model increased to 0.691, that shows a significant improvement in goodness-of-fit than the global OLS model, which means that spatial heterogeneity of some independent variables is another important factor that influences the relationship with heat-related morbidity in Maricopa County. Among these variables, population aged 65 and older, the Hispanic population, disability, vehicle ownership, and housing occupancy have much stronger local effects than other variables.Keywords: census, empirical modeling, heat-related morbidity, spatial analysis
Procedia PDF Downloads 1264927 Perspectives on Educational Psychological Support Services in New Zealand and South African Schools
Authors: Johnnie Hay
Abstract:
New Zealand is well known for its natural beauty, diversity of people but also for its strong focus on mental health through the provision of a vast network of psycho-social support services. South African-trained psychologists often make New Zealand their new home when emigrating - as it is relatively simple to slot into the well-established mental health system. South Africa is bigger in size, population, GDP and probably people diversity than New Zealand but struggles to provide adequate educational and psychological support services to schools. This is mainly due to budgetary pressures brought about by the imperative to first ensure that the approximately 13 million learners all have a teacher in front of their classes and at an average ratio of not more than 40 learners per class. In this paper, perspectives on educational and psychological support in New Zealand and South African schools will be shared. Through basic qualitative research encompassing semi-structured interviews with two South African educational psychologists who returned from New Zealand, supplemented by document analysis, the New Zealand situation will be scrutinized. South African perspectives will be obtained through a number of semi-structured interviews and questionnaires administered by education support services specialists working in district-based support teams in three provinces of the country. This research is in process, but preliminary findings indicate large disparities between the two countries' emphasis, funding, post provisioning and structure regarding educational and psychological support services.Keywords: educational psychological support services, support for learners experiencing special needs, education support services, diverse learner population
Procedia PDF Downloads 714926 Impact of Economic Crisis on Secondary Education in Anambra State
Authors: Stella Nkechi Ezeaku, Ifunanya Nkechi Ohamobi
Abstract:
This study investigated the impact of economic crisis on education in Anambra state. The population of the study comprised of all principals and teachers in Anambra state numbering 5,887 (253 principles and 5,634 teachers). To guide the study, three research questions and one hypothesis were formulated correlational design was adopted. Stratified random sampling technique was used to select 200 principals and 300 teachers as respondents for the study. A researcher-developed instrument tagged Impact of Economic Crisis on Education questionnaire (IECEQ) was used to collect data needed for the study. The instrument was validated by experts in measurement and evaluation. The reliability of the instrument was established using randomly selected members of the population who did not take part in the study. The data obtained was analyzed using Cronbach alpha technique and reliability co-efficient of .801 and .803 was obtained. The data were analyzed using simple and Multiple Regression Analysis. The formulated hypothesis was tested at .05 level of significance. Findings revealed that: there is a significant relationship between economic crisis and realization of goals of secondary education. The result also shows that economic crisis affect students' academic performance, teachers' morale and productivity and principals' administrative capability. This study therefore concludes that certain strategies must be devised to minimize the impact of economic crisis on secondary education. It is recommended that all stakeholders to education should be more resourceful and self-sufficient in order to cushion the effects of economic crisis currently gripping most world economies Nigeria inclusive.Keywords: impact, economic, crisis, education
Procedia PDF Downloads 2444925 Population Pharmacokinetics of Levofloxacin and Moxifloxacin, and the Probability of Target Attainment in Ethiopian Patients with Multi-Drug Resistant Tuberculosis
Authors: Temesgen Sidamo, Prakruti S. Rao, Eleni Akllilu, Workineh Shibeshi, Yumi Park, Yong-Soon Cho, Jae-Gook Shin, Scott K. Heysell, Stellah G. Mpagama, Ephrem Engidawork
Abstract:
The fluoroquinolones (FQs) are used off-label for the treatment of multidrug-resistant tuberculosis (MDR-TB), and for evaluation in shortening the duration of drug-susceptible TB in recently prioritized regimens. Within the class, levofloxacin (LFX) and moxifloxacin (MXF) play a substantial role in ensuring success in treatment outcomes. However, sub-therapeutic plasma concentrations of either LFX or MXF may drive unfavorable treatment outcomes. To the best of our knowledge, the pharmacokinetics of LFX and MXF in Ethiopian patients with MDR-TB have not yet been investigated. Therefore, the aim of this study was to develop a population pharmacokinetic (PopPK) model of levofloxacin (LFX) and moxifloxacin (MXF) and assess the percent probability of target attainment (PTA) as defined by the ratio of the area under the plasma concentration-time curve over 24-h (AUC0-24) and the in vitro minimum inhibitory concentration (MIC) (AUC0-24/MIC) in Ethiopian MDR-TB patients. Steady-state plasma was collected from 39 MDR-TB patients enrolled in the programmatic treatment course and the drug concentrations were determined using optimized liquid chromatography-tandem mass spectrometry. In addition, the in vitro MIC of the patients' pretreatment clinical isolates was determined. PopPK and simulations were run at various doses, and PK parameters were estimated. The effect of covariates on the PK parameters and the PTA for maximum mycobacterial kill and resistance prevention was also investigated. LFX and MXF both fit in a one-compartment model with adjustments. The apparent volume of distribution (V) and clearance (CL) of LFX were influenced by serum creatinine (Scr), whereas the absorption constant (Ka) and V of MXF were influenced by Scr and BMI, respectively. The PTA for LFX maximal mycobacterial kill at the critical MIC of 0.5 mg/L was 29%, 62%, and 95% with the simulated 750 mg, 1000 mg, and 1500 mg doses, respectively, whereas the PTA for resistance prevention at 1500 mg was only 4.8%, with none of the lower doses achieving this target. At the critical MIC of 0.25 mg/L, there was no difference in the PTA (94.4%) for maximum bacterial kill among the simulated doses of MXF (600 mg, 800 mg, and 1000 mg), but the PTA for resistance prevention improved proportionately with dose. Standard LFX and MXF doses may not provide adequate drug exposure. LFX PopPK is more predictable for maximum mycobacterial kill, whereas MXF's resistance prevention target increases with dose. Scr and BMI are likely to be important covariates in dose optimization or therapeutic drug monitoring (TDM) studies in Ethiopian patients.Keywords: population PK, PTA, moxifloxacin, levofloxacin, MDR-TB patients, ethiopia
Procedia PDF Downloads 1204924 Educators’ Perceived Capacity to Create Inclusive Learning Environments: Exploring Individual Competencies and District Policy
Authors: Thuy Phan, Stephanie Luallin
Abstract:
Inclusive education policies have demonstrated benefits for students with and without disabilities in the US. There are several laws that relate to inclusive education, such as 'No Child Left Behind', 'The Individuals with Disabilities Education Act'. However, the application of these inclusive education laws and policies vary per state and school district. Classroom teachers in an inclusive classroom often experience confusion as to how to apply these policies in order to create appropriate inclusive learning environments that meet the abilities and needs of their diverse student population. The study aims to investigate teachers’ perspective of their capacities to create an appropriate learning environment for their diverse student population including students with disabilities. Qualitative method is implemented in this study, using open-end interview questions to investigate teachers’ perspective of their capacities to create an appropriate inclusive learning environment for all students based on current inclusive education laws and district policies in the state of Colorado, USA. These findings may indicate a lack of confidence in teachers’ capacity to create appropriate inclusive learning environments based on laws and district policies; including challenges that classroom teachers may experience in creating inclusive learning environments. The purpose of this study is to examine the adequate preparation of classroom teachers in creating inclusive classrooms with the intent of determining implications for developing policies in inclusive education.Keywords: educator’s capacity, inclusive education, inclusive learning environment, policy
Procedia PDF Downloads 1704923 An Immersive Serious Game for Firefighting and Evacuation Training in Healthcare Facilities
Authors: Anass Rahouti, Guillaume Salze, Ruggiero Lovreglio, Sélim Datoussaïd
Abstract:
In healthcare facilities, training the staff for firefighting and evacuation in real buildings is very challenging due to the presence of a vulnerable population in such an environment. In a standard environment, traditional approaches, such as fire drills, are often used to train the occupants and provide them with information about fire safety procedures. However, those traditional approaches may be inappropriate for a vulnerable population and can be inefficient from an educational viewpoint as it is impossible to expose the occupants to scenarios similar to a real emergency. Immersive serious games could be used as an alternative to traditional approaches to overcome their limitations. Serious games are already being used in different safety domains such as fires, earthquakes and terror attacks for several building types (e.g., office buildings, train stations, tunnels, etc.). In this study, we developed an immersive serious game to improve the fire safety skills of staff in healthcare facilities. An accurate representation of the healthcare environment was built in Unity3D by including visual and audio stimuli inspired from those employed in commercial action games. The serious game is organised in three levels. In each of them, the trainee is presented with a specific fire emergency and s/he can perform protective actions (e.g., firefighting, helping non-ambulant occupants, etc.) or s/he can ignore the opportunity for action and continue the evacuation. In this paper, we describe all the steps required to develop such a prototype, as well as the key questions that need to be answered, to develop a serious game for firefighting and evacuation in healthcare facilities.Keywords: fire safety, healthcare, serious game, training
Procedia PDF Downloads 4524922 Examining the Predictors of Non-Urgent Emergency Department Visits: A Population Based Study
Authors: Maher El-Masri, Jamie Crawley, Judy Bornais, Abeer Omar
Abstract:
Background: Misuse of Emergency Department (ED) for non-urgent healthcare results in unnecessary crowdedness that can result in long ED waits and delays in treatment, diversion of ambulances to other hospitals, poor health outcomes for patients, and increased risk of death Objectives: The main purpose of this study was to explore the independent predictors of non-urgent ED visits in Erie St. Clair LHIN. Secondary purposes of the study include comparison of the rates of non-urgent ED visits between urban and rural hospitals Design: A secondary analysis of archived population-based data on 597,373 ED visits in southwestern Ontario Results The results suggest that older (OR = .992; 95% CI .992 – .993) and female patients (OR = .940; 95% CI .929 - .950) were less likely to visit ED for non-urgent causes. Non-urgent ED visits during the winter, spring, and fall were 13%, 5.8%, and 7.5%, respectively, lesser than they were during the summer time. The data further suggest that non-urgent visits were 19.6% and 21.3% less likely to occur in evening and overnight shifts compared to the day shift. Non-urgent visits were 2.76 times more likely to present to small community hospitals than large community hospitals. Health care providers were 1.92 times more likely to refer patients with non-urgent health problem to the ED than the decision taken by patients, family member or caretakers. Conclusion: In conclusion, our study highlights a number of important factors that are associated with inappropriate use of ED visits for non-urgent health problems. Knowledge of these factors could be used to address the issue of unnecessary ED crowdedness.Keywords: emergency department, non-urgent visits, predictors, logistic regression
Procedia PDF Downloads 2474921 Pattern Discovery from Student Feedback: Identifying Factors to Improve Student Emotions in Learning
Authors: Angelina A. Tzacheva, Jaishree Ranganathan
Abstract:
Interest in (STEM) Science Technology Engineering Mathematics education especially Computer Science education has seen a drastic increase across the country. This fuels effort towards recruiting and admitting a diverse population of students. Thus the changing conditions in terms of the student population, diversity and the expected teaching and learning outcomes give the platform for use of Innovative Teaching models and technologies. It is necessary that these methods adapted should also concentrate on raising quality of such innovations and have positive impact on student learning. Light-Weight Team is an Active Learning Pedagogy, which is considered to be low-stake activity and has very little or no direct impact on student grades. Emotion plays a major role in student’s motivation to learning. In this work we use the student feedback data with emotion classification using surveys at a public research institution in the United States. We use Actionable Pattern Discovery method for this purpose. Actionable patterns are patterns that provide suggestions in the form of rules to help the user achieve better outcomes. The proposed method provides meaningful insight in terms of changes that can be incorporated in the Light-Weight team activities, resources utilized in the course. The results suggest how to enhance student emotions to a more positive state, in particular focuses on the emotions ‘Trust’ and ‘Joy’.Keywords: actionable pattern discovery, education, emotion, data mining
Procedia PDF Downloads 984920 Comparing Media-Based Strategies of Identity Formation in Chicanos and Cuban-Americans
Authors: Kwang Yeon Kim
Abstract:
This paper will explore the directly proportional relationship between the influence of Hispanophone media in U.S. markets and Hispanic population growth. Though this growth has origins across south and central America, in U.S. media markets Mexican and Cuban immigrants, have traditionally been considered the most influential. Having endured significant historical discrimination, disparagement, and ethnic framing from conventional Anglophone media, such groups have sought to form their own identities as media consuming and producing Americans of Latin American origin. Although immigrants to the U.S. have traditionally faced obstacles in access to education, children of Mexican-Americans (Chicanos) and Cuban-Americans have made significant progress in overcoming these obstacles, partly explaining their media dominance. This is particularly true in the case of Cuban-Americans, for whom such media presence is not predicted by share of population. By conducting comparative studies of Chicano media and Cuban-Americans media, common ground was found in strategies of reliance on media-driven identity formation. In contrast to the mainstream media portrayal of Latino/as with limiting, negative stereotypes, Spanish-language media’s goal is to form the identity of being Latino for those living in the United States. Providing both news from countries of origin and local news within the United States, Chicano and Cuban-American media performs rituals of recollection while rooting such populations in more proximate media paradigms.Keywords: Chicano identity, Cuban-Americans, Hispanophone media, Latino/a community
Procedia PDF Downloads 2074919 Design and in Slico Study of the Truncated Spike-M-N SARS-CoV-2 as a Novel Effective Vaccine Candidate
Authors: Aghasadeghi MR., Bahramali G., Sadat SM., Sadeghi SA., Yousefi M., Khodaei K., Ghorbani M., Sadat Larijani M.
Abstract:
Background:The emerging COVID-19 pandemic is a serious concernfor the public health worldwide. Despite the many mutations in the virus genome, it is important to find an effective vaccine against viral mutations. Therefore, in current study, we aimed at immunoinformatic evaluation of the virus proteins immunogenicity to design a preventive vaccine candidate, which could elicit humoral and cellular immune responses as well. Methods:Three antigenic regions are included;Spike, Membrane, and Nucleocapsid amino acid sequences were obtained, and possible fusion proteins were assessed andcompared by immunogenicity, structural features, and population coverage. The best fusion protein was also evaluated for MHC-I and MHC-II T-cell epitopes and the linear and conformational B-cell epitopes. Results: Among the four predicted models, the truncated Spike protein in fusion with M and N proteins is composed of 24 highly immunogenic human MHC class I and 29 MHC class II, along with 14 B-cell linear and 61 discontinues epitopes. Also, the selected protein has high antigenicity and acceptable population coverage of 82.95% in Iran and 92.51% in Europe. Conclusion: The data indicate that the truncated Spike-M-N SARS-CoV-2form which could be potential targets of neutralizing antibodies. The protein also has the ability to stimulate humoral and cellular immunity. The in silico study provided the fusion protein as a potential preventive vaccine candidate for further in vivo evaluation.Keywords: SARS-CoV-2, immunoinformatic, protein, vaccine
Procedia PDF Downloads 2234918 Variability in Contraception Choices and Abortion Rates among Female Garment Factory Workers in Urban and Rural Cambodia
Authors: Olalekan Olaluwoye, Joanne Williams, Elizabeth Hoban
Abstract:
Background: Modern contraceptives are effective in preventing unwanted pregnancies and therefore the potential to reduce abortion rates. There is a need for information about how rates of contraceptive use and abortion vary across Cambodia and the relationship between the prevalence of modern contraception use and abortion rates. This study compares the use of contraception and abortion among female garment factory workers in rural and urban areas of Cambodia. Method: Cross-sectional surveys were conducted with 1701 women working in eleven garment factories in rural and urban areas of Cambodia. Sexual and reproductive health data were collected using Audio-Assisted Survey Interviews and analysed using STATA 14 software. Findings: Over 70% of the respondents were less than 30 years of age across both rural and urban settings and over 50% have only primary education, thus the study population was largely young women with limited education. A significantly higher proportion of the rural women earned over $200 in the previous month compared with their urban counterparts. The majority of the urban women (51.5%) were married, while single women (46.9%) made up the largest group working in the rural factories. A significantly larger proportion of women in the rural areas (83.9%) were sexually active compared to the urban women (50.9%). More women from the rural areas (41.4%) had been pregnant at some time compared with the urban population (37.7%). The use of any contraceptive method among sexually active women was significantly higher in the rural areas (80.1%) compared to the urban areas (65.7%) with p-value=0.000. However, among those women who used contraception, the prevalence of modern contraception use was slightly higher in the urban population (68.8% urban, 63.4% rural, p-value=0.1). For women who had a history of pregnancy the abortion prevalence was higher among rural women (43.8%) compared to their urban counterparts (37.7%). Regression analysis showed that after adjustment for the demographic variables (age, relationship status, income, education) only age and relationship status had a significant influence on the use of modern contraception.Single females who were sexually active and older women, who had potentially completed their families, were more likely to choose modern contraception. Conclusion: Although overall the use of contraception was higher among rural women, the use of modern contraception was higher among urban women.This finding may partly explain the higher rates of abortion among women in the rural areas as traditional contraception methods have higher failure rates and are more likely to result in an unplanned pregnancy.Despite the regional variation, the high rates of abortion across the country suggest there is a need for improve education on family planning among female garment factory workers in Cambodia.Keywords: abortion, Cambodia, contraception, garment factory
Procedia PDF Downloads 1504917 Cultural Competence and Healthcare Challenges of Migrants in South Wales United Kingdom
Authors: Qirat Naz, Abasiokpon Udoakah
Abstract:
In developed countries, global migration is diversifying. The minority ethnic population, including refugees and asylum seekers who, fled their home countries due to war, terrorism, oppression, or natural disasters, and returning home is dangerous for them. They need sanctuary and peaceful environment in host countries. They begin the process of acculturation, in which a person adopts the social mores and behavioral patterns of the dominant culture, yet they still have unique multicultural needs that the dominant society fails to address. The aim of this research is to provide a holistic understanding of the living experiences of a minority population, particularly migrants, including asylum seekers and refugees, in the health and social care system of South Wales. The purpose of this study is to investigate three research objectives: the multicultural health care needs of minorities, as well as the barriers to seeking health and social care facilities. There are Welsh policies for promoting cultural competence in the health and social care sectors; this research will explore the implications and impact of these policies on the target population. This research study will be conducted using qualitative research methods, tools, and techniques. This research is an inductive approach to coming up with a grounded theory. The sample will be divided into two groups: migrants and professionals providing any kind of services to migrants; each group will contain 30 participants. Interpretive phenomenological analysis would be utilized during the process of coding and developing the main themes of this research. The positionality of the researcher would be minimized by unloaded and open-ended questions, researcher’s work experience in research, continuous evaluation of her positionality, daily base reflection of fieldwork and seeking the help of male and female gatekeepers. The research findings would be based on emic perspective, and by documenting the emic perspective of minorities, this research will contribute to the knowledge of appropriate channels, including organizations, academics, and policymakers, to discover possible solutions and coping mechanisms to deal with the challenges and meet the multicultural demands of minorities. This research will provide a more in-depth understanding of minorities and will help to promote the diversity of health and social care in South Wales.Keywords: migration, migrants, cultural competence, cultural barriers, healthcare challenges
Procedia PDF Downloads 604916 Evaluation of the Pain of Patients with Chronic Renal Disease in Hemodialysis
Authors: Fabiana Souza Orlandi, Izabel Cristina Chavez Gomes, Barbara Isabela De Paula Morais, Ana Carolina Ottaviani
Abstract:
Chronic Kidney Disease (CKD) is considered a public health problem. Patients who present CKD in their more advanced stages usually present several biopsychosocial changes, which may include pain. Pain can be considered subjective and personal, and its perception is characterized as a multidimensional experience. The objective of this study was to evaluate the level and descriptors of pain of adults and elderly patients with chronic kidney disease, through the Multidimensional Pain Evaluation Scale (EMADOR). This is a descriptive cross-sectional study with a quantitative approach. The sample consisted of 100 subjects with CKD in hemodialysis treatment at a Renal Replacement Therapy Service in the interior of the state of São Paulo. Data were collected through an individual interview, using a Sociodemographic Characterization and Multidimensional Pain Evaluation Scale (EMADOR). All ethical precepts were respected. The majority of the respondents were men (61.0%), white (56.0%) and with a high school education (34.0%). Regarding the pain of the individuals, 89 patients reported pain, with Chronic Pain predominating (50.0%, n = 50), followed by Acute Pain (39.0%, n = 39). Of the subjects who presented acute pain most of the 89.0% described the pain felt as unbearable, and of those who presented chronic pain, 35.0% described the pain felt as painful, unbearable and uncomfortable. It was concluded that there was a significant presence of pain, being the chronic pain dominant in the studied population. Faced with such factors, the present study motivates researches in this population, in order to establish interventions with the objective of improving the quality of life of these individuals.Keywords: pain, chronic kidney disease, dialysis, evaluation
Procedia PDF Downloads 4524915 Clinical Impact of Ultra-Deep Versus Sanger Sequencing Detection of Minority Mutations on the HIV-1 Drug Resistance Genotype Interpretations after Virological Failure
Authors: S. Mohamed, D. Gonzalez, C. Sayada, P. Halfon
Abstract:
Drug resistance mutations are routinely detected using standard Sanger sequencing, which does not detect minor variants with a frequency below 20%. The impact of detecting minor variants generated by ultra-deep sequencing (UDS) on HIV drug-resistance (DR) interpretations has not yet been studied. Fifty HIV-1 patients who experienced virological failure were included in this retrospective study. The HIV-1 UDS protocol allowed the detection and quantification of HIV-1 protease and reverse transcriptase variants related to genotypes A, B, C, E, F, and G. DeepChek®-HIV simplified DR interpretation software was used to compare Sanger sequencing and UDS. The total time required for the UDS protocol was found to be approximately three times longer than Sanger sequencing with equivalent reagent costs. UDS detected all of the mutations found by population sequencing and identified additional resistance variants in all patients. An analysis of DR revealed a total of 643 and 224 clinically relevant mutations by UDS and Sanger sequencing, respectively. Three resistance mutations with > 20% prevalence were detected solely by UDS: A98S (23%), E138A (21%) and V179I (25%). A significant difference in the DR interpretations for 19 antiretroviral drugs was observed between the UDS and Sanger sequencing methods. Y181C and T215Y were the most frequent mutations associated with interpretation differences. A combination of UDS and DeepChek® software for the interpretation of DR results would help clinicians provide suitable treatments. A cut-off of 1% allowed a better characterisation of the viral population by identifying additional resistance mutations and improving the DR interpretation.Keywords: HIV-1, ultra-deep sequencing, Sanger sequencing, drug resistance
Procedia PDF Downloads 3354914 Assess the Accessibility to Culturally Competent Mental Health Services for Haitian Communities in New York State
Authors: Natacha Julceus Fabien, Maryse Emmanuel Garcy
Abstract:
Mental illness encompasses more than two hundred types of mental troubles, and more than half of the American population is at risk of being affected. If not effectively treated, mental illness can have dire consequences on health, the economy, and society. New York State, the second state after Florida with the most prominent Haitian/American, counted 180,710 inhabitants distributed in 60321 households in 2021, with almost half 46.4% being less than 35 years old. Studies show that while blacks are resilient, they are more likely to have severe mental diseases leading to disabilities compared to their white counterparts. Cultural competence in mental health services can narrow health disparities. Achieving this cultural competency in the health system involves good coordination in a robust health system where everyone is ready to contribute to its practical implementation. An effective way to address the issue is to have good baseline knowledge. However, there is not enough data that specifically informs on the accessibility to culturally competent mental health services for the Haitian American communities in New York. The purpose of this Community Needs Assessment is to assess the accessibility of minorities, particularly Haitian communities in New York, to culturally competent mental health services. This assessment will be conducted in the ten regions of New York State. Providers, clients, members of the community, and minority organizations will be recruited to collect quantitative and qualitative data. The quantitative part will be done in two surveys, one collecting primary data from the general population receiving the services and the other from health providers that provide health services. The questions and answers will be saved in Excel and analyzed on SPSS. For qualitative data, focus groups and in-depth guide interviews will be conducted and analyzed through Strengths, Weaknesses, Opportunities, and Threats (SWOT) Analysis of how the population and critical informants understand and identify cultural competency components in the mental health system. This research will be presented at the HAFALI research forum and specific minority organizations in New York. It will be submitted to mental health conferences and specific journals for publication. It will be shared with the heads of the community health service and the heads of the New York State Office of Mental Health. This needs assessment will be used as a tool to improve access to culturally competent mental health services nationally and worldwide.Keywords: mental health, minorities, New York, needs assessment
Procedia PDF Downloads 84913 Yoga as a Tool for Public Health
Authors: Divya Kanchibhotla
Abstract:
Of all the major health threats to emerge, none has challenged the very foundation of public health so profoundly as the rise of non-communicable diseases (NCD). Encouraging a holistic health approach encompasses the community’s well-being. Competent public health grounded with holistic health approach can lay a better foundation in the modern world. Yoga has been increasingly explored as an adjunct therapy to major disorders. This study explores the efficacy of Yoga as a tool for public health. A survey was administered to 5500 adults, and 300 teens were selected from 25 states of India. The study explored the differences in health, happiness, and sustainable living between Yoga-practitioners and Non-yoga practitioners. The study also explored the practice and habits of yoga practitioners (frequency, place, reasons to practice) and Health, Happiness, and Sustainable Living. The subjects were grouped based on age, education, experience in yoga (years of practice), and occupational background. The study population comprised of 54% males and 46% females. Majority of the respondents (59%) were from 18 to 30 years age group. The study indicated that 96.4% of the total respondents have heard of Yoga. However, only 46.8% of the total study population practice yoga (YP) and the rest 53.2% were non-practitioners (NP). From a perspective of how Yoga and health, 72.7% yoga practitioners asserted a peaceful and happy life, 71.9% yoga practitioners felt satisfaction in life, and 70.2 % yoga practitioners had satisfactory health. 61.9% of yoga practitioners report being vegetarian, not eating junk food, and not drinking alcohol than 38.1% Non-Practitioners population. 47% of yoga practitioners found themselves to be more sensitive to the environment compared to only 40% of non-practitioners. India has been witnessing an unprecedented rise in the NCDs, accounting for 61% deaths. The importance of yoga as an adjunct therapy for various disorders and diseases is gaining momentum across the globe. There are various studies on yoga that have indicated benefits of yoga as a unique holistic approach towards lifestyle and a consistent, complementary solution that could be adopted for long-term viability for a well being. The comprehensive study is the first of its kind that takes a holistic look at the prevalence of Yoga for public health in India. Our study is unique and stands out as it is detailed in its outlook with extensive coverage of almost the whole country (surveying 25 out of 29 states) and contemplates on the benefits to an individual at the grass-root level – physical, mental and social outlook. The insights from the study will enable the health care systems and grassroots organizations to make the holistic practice of Yoga accessible to spread sustainable living for a healthy community.Keywords: non-communicable disease (NCD), sustainable development goal (SDG 3), public health, healthy living
Procedia PDF Downloads 1954912 Stature Prediction from Anthropometry of Extremities among Jordanians
Authors: Amal A. Mashali, Omar Eltaweel, Elerian Ekladious
Abstract:
Stature of an individual has an important role in identification, which is often required in medico-legal practice. The estimation of stature is an important step in the identification of dismembered remains or when only a part of a skeleton is only available as in major disasters or with mutilation. There is no published data on anthropological data among Jordanian population. The present study was designed in order to find out relationship of stature to some anthropometric measures among a sample of Jordanian population and to determine the most accurate and reliable one in predicting the stature of an individual. A cross sectional study was conducted on 336 adult healthy volunteers , free of bone diseases, nutritional diseases and abnormalities in the extremities after taking their consent. Students of Faculty of Medicine, Mutah University helped in collecting the data. The anthropometric measurements (anatomically defined) were stature, humerus length, hand length and breadth, foot length and breadth, foot index and knee height on both right and left sides of the body. The measurements were typical on both sides of the bodies of the studied samples. All the anthropologic data showed significant relation with age except the knee height. There was a significant difference between male and female measurements except for the foot index where F= 0.269. There was a significant positive correlation between the different measures and the stature of the individuals. Three equations were developed for estimation of stature. The most sensitive measure for prediction of a stature was found to be the humerus length.Keywords: foot index, foot length, hand length, humerus length, stature
Procedia PDF Downloads 3064911 Computer Based Identification of Possible Molecular Targets for Induction of Drug Resistance Reversion in Multidrug Resistant Mycobacterium Tuberculosis
Authors: Oleg Reva, Ilya Korotetskiy, Marina Lankina, Murat Kulmanov, Aleksandr Ilin
Abstract:
Molecular docking approaches are widely used for design of new antibiotics and modeling of antibacterial activities of numerous ligands which bind specifically to active centers of indispensable enzymes and/or key signaling proteins of pathogens. Widespread drug resistance among pathogenic microorganisms calls for development of new antibiotics specifically targeting important metabolic and information pathways. A generally recognized problem is that almost all molecular targets have been identified already and it is getting more and more difficult to design innovative antibacterial compounds to combat the drug resistance. A promising way to overcome the drug resistance problem is an induction of reversion of drug resistance by supplementary medicines to improve the efficacy of the conventional antibiotics. In contrast to well established computer-based drug design, modeling of drug resistance reversion still is in its infancy. In this work, we proposed an approach to identification of compensatory genetic variants reducing the fitness cost associated with the acquisition of drug resistance by pathogenic bacteria. The approach was based on an analysis of the population genetic of Mycobacterium tuberculosis and on results of experimental modeling of the drug resistance reversion induced by a new anti-tuberculosis drug FS-1. The latter drug is an iodine-containing nanomolecular complex that passed clinical trials and was admitted as a new medicine against MDR-TB in Kazakhstan. Isolates of M. tuberculosis obtained on different stages of the clinical trials and also from laboratory animals infected with MDR-TB strain were characterized by antibiotic resistance, and their genomes were sequenced by the paired-end Illumina HiSeq 2000 technology. A steady increase in sensitivity to conventional anti-tuberculosis antibiotics in series of isolated treated with FS-1 was registered despite the fact that the canonical drug resistance mutations identified in the genomes of these isolates remained intact. It was hypothesized that the drug resistance phenotype in M. tuberculosis requires an adjustment of activities of many genes to compensate the fitness cost of the drug resistance mutations. FS-1 cased an aggravation of the fitness cost and removal of the drug-resistant variants of M. tuberculosis from the population. This process caused a significant increase in genetic heterogeneity of the Mtb population that was not observed in the positive and negative controls (infected laboratory animals left untreated and treated solely with the antibiotics). A large-scale search for linkage disequilibrium associations between the drug resistance mutations and genetic variants in other genomic loci allowed identification of target proteins, which could be influenced by supplementary drugs to increase the fitness cost of the drug resistance and deprive the drug-resistant bacterial variants of their competitiveness in the population. The approach will be used to improve the efficacy of FS-1 and also for computer-based design of new drugs to combat drug-resistant infections.Keywords: complete genome sequencing, computational modeling, drug resistance reversion, Mycobacterium tuberculosis
Procedia PDF Downloads 263