Search results for: Munazza A. Mirza

Authors: Fazle Rabbi, Mashuda Khanom Tithi, Tasnim Mirza, Sanjida Rowshan Anannya, Ahmed Hossain

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Background: Low Back Pain (LBP) is one of the common health problems among the garment workers that causes workers absenteeism from the work. The purpose of the study is to identify the association between occupational factors and LBP among the female garment workers in Bangladesh. Materials and Methods: A cross-sectional study was conducted with 487 female garment workers from three compliant garment factories of Bangladesh. Face-to-face interview on four different LBP measures along with questions on socio-demographic, occupational, and physical factors were used to collect the data. Result: The prevalence rates for LBP lasts for at least one day during the last six months, chronic pain, intense pain, and seeking medical care for LBP were found 63.04%, 38.60%, 13.76%, and 18.89%, respectively among the female garments workers. The multivariate logistic regression analysis indicates that duration of employment (>5 years), regular weight bearing and extended weekly working hours (>48 hours) are positively associated with LBP. Besides, age, BMI, family income, marital status and number of children are also found positively associated with the LBP measures. Conclusion: The prevalence of LBP among female garment workers in Bangladesh is found high. The duration of employment (>5 years), regular weight bearing and extended weekly working hours (>48 hours) play a significant role in developing LBP among the female workers. Factories need to consider training programs on the appropriate technique of weight bearing. It is also important to conduct regular screening programs to identify LBP, especially with married, overweight/obese and older age group to reduce the occurrence of LBP.

Keywords: Bangladesh, garment workers, low back pain, occupational health

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Authors: Zoaib Mirza

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Half of the Muslim countries in the world have declared Islam the state religion in their constitutions. Yet, none of these countries have implemented authentic Islamic laws in line with the Quran (Holy Book), practices of Prophet Mohammad (P.B.U.H) called the Sunnah, and his four successors known as the Rightly Guided - Khalifa. Since their independence, these countries have adopted different government systems like Democracy, Dictatorship, Republic, Communism, and Monarchy. Instead of benefiting the people, these government systems have put these countries into political, social, and economic crises. These Islamic countries do not have equal representation and membership in worldwide political forums. Western countries lead these forums. Therefore, it is now imperative for the Muslim leaders of all these countries to collaborate, reset, and implement the original Islamic form of government, which led to the prosperity and success of people, including non-Muslims, 1400 years ago. They should unite as one nation under Khalifat, which means establishing the authority of Allah (SWT) and following the divine commandments related to the social, political, and economic systems. As they have declared Islam in their constitution, they should work together to apply the divine framework of the governance revealed by Allah (SWT) and implemented by Prophet Mohammad (P.B.U.H) and his four successors called Khalifas. This paper provides an overview of the downfall and the end of the Khalifat system by 1924, the ways in which the West caused political, social, and economic crises in the Muslim countries, and finally, a summary of the social, political, and economic systems implemented by the Prophet Mohammad (P.B.U.H) and his successors, Khalifas, called the Rightly Guided – Hazrat Abu Bakr (RA), Hazrat Omar (RA), Hazrat Usman (RA), and Hazrat Ali (RA).

Keywords: khalifat, khilafat-e-Rashida, the rightly guided, colonization, capitalism, neocolonization, government systems

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Authors: Zoaib Mirza

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Pakistan is an Islamic country that got its partition from India in 1947 so that the people could practice the religion of Islam. The ideology of Pakistan was based on the notion that sovereignty only belonged to God Almighty (in Arabic, God means “Allah”), and Muslims will live in accordance with Islam principles. The Quran (Holy Book) and Sunnah (authentic practices of Prophet Mohammad, Peace Be Upon Him, that explains the application of the Quran) are foundations of the Islamic principles. It has been over 75 years, but unfortunately, Pakistan, due to its own political, social, and economic mistakes, is responsible for not being able to become a true Islamic nation to justify its partition from India. The rationale for writing this paper is to analyze the factors that led to changes in the democratic movements impacting the country's political, social, and economic growth. The methodology to examine the historical and political context of Pakistan’s history is by referencing the scholarly work of Israr Ahmed, a Pakistani Islamic theologian, philosopher, and Islamic scholar. While from a Western perspective, Karl Marx, Mar Weber, Hannah Arendt, Sheldon Wolin, Paulo Freire, and Jacques Ranciere's philosophies specific to totalitarianism, politics, military rule, religion, capitalism, and superpower are used as the framework to analyze Pakistan’s democracy. The study's findings conclude that Pakistan's democracy is unstable and has been impacted by military and civilian governance, which led to political, social, and economic downfall. To improve the current situation, the citizens of Pakistan have to realize that the success of a nation is only dependent on the level of consciousness of the leader and not the political system. Therefore, it is the responsibility of every citizen to be conscious of how they select their leader and take responsibility for the current situation in Pakistan.

Keywords: Pakistan, Islam, democracy, totalitarianism, military, religion, capitalism

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Authors: Sumera, Sanila Amber, Fatima Javed Mirza, Amjad Ali, Saadia Zahid

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Glioblastoma multiforme (GBM) is a widely spread and fatal primary brain tumor with an increased risk of relapse in spite of aggressive treatment. The current procedures for GBM diagnosis include invasive procedures i.e. resection or biopsy, to acquire tumor mass. Implementation of negligibly invasive tests as a potential diagnostic technique and biofluid-based monitoring of GBM stresses on discovering biomarkers in CSF and blood. Therefore, we performed a comprehensive in silico analysis to identify potential circulating biomarkers for GBM. Initially, six gene and protein databases were utilized to mine brain-specific proteins. The resulting proteins were filtered using a channel of five tools to predict the secretory proteins. Subsequently, the expression profile of the secreted proteins was verified in the brain and blood using two databases. Additional verification of the resulting proteins was done using Plasma Proteome Database (PPD) to confirm their presence in blood. The final set of proteins was searched in literature for their relationship with GBM, keeping a special emphasis on secretome proteome. 2145 proteins were firstly mined as brain-specific, out of which 69 proteins were identified as secretory in nature. Verification of expression profile in brain and blood eliminated 58 proteins from the 69 proteins, providing a final list of 11 proteins. Further verification of these 11 proteins further eliminated 2 proteins, giving a final set of nine secretory proteins i.e. OPCML, NPTX1, LGI1, CNTN2, LY6H, SLIT1, CREG2, GDF1 and SERPINI1. Out of these 9 proteins, 7 were found to be linked to GBM, whereas 2 proteins are not investigated in GBM so far. We propose that these secretory proteins can serve as potential circulating biomarker signatures of GBM and will facilitate the development of minimally invasive diagnostic methods and novel therapeutic interventions for GBM.

Keywords: glioblastoma multiforme, secretory proteins, brain secretome, biomarkers

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Authors: Kashan Bashir, Salah Naji Ahmed Sufyan, Mirza Umar Baig

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In this study, n-dodecane, tetralin, decalin, and tetramethybenzene (TMBE) were used as model compounds of alkanes, naphthenic-aromatic, cycloalkanes and alkyl-benzenes presented in hydro-diesel. The catalytic cracking properties of four model compounds over Y zeolite catalyst (Y-Cat.) and ZSM-5 zeolite catalysts (ZSM-5-Cat.) were probed. The experiment results revealed that high conversion of macromolecular paraffin and naphthenic aromatics were achieved over Y-Cat, whereas its low cracking activity of intermediate products micromolecules paraffin and olefin and high activity of hydride transfer reaction goes against the production of value-added products (light olefin and gasoline). In contrast, despite the fact that the hydride transfer reaction was greatly inhabited over ZSM-5-Cat, the low conversion of macromolecules was observed attributed to diffusion limitations. Interestingly, the mixed catalyst compensates for the shortcomings of the two catalysts, and a “relay reaction” between Y-Cat and ZSM-5-Cat was proposed. Specifically, the added Y-Cat acts as a “pre-cracking booster site” and promotes macromolecules conversion. The addition of ZSM-5-Cat not only significantly suppresses the hydride transfer reaction but also contributes to the cracking of immediate products paraffin and olefin into ethylene and propylene, resulting in a high yield of alkyl-benzene (gasoline), ethylene, and propylene with a low yield of naphthalene (LCO) and coke. The catalytic cracking evaluation experiments of mixed hydro-LCO were also performed to further clarify the “relay reaction” above, showing the highest yield of LPG and gasoline over mixed catalyst. The results indicate that the Y-cat and ZSM-5-cat have a synergistic effect on the conversion of hydro-diesel and corresponding value-added product yield and selective coke yield.

Keywords: synergistic effect, hydro-diesel cracking, FCC, zeolite catalyst, ethylene and propylene

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Authors: Mirza Waseem Abbas, Syed Danish Raza

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For many countries agriculture is still the major force driving the economy and a critically important socioeconomic sector, despite exceptional industrial development across the globe. In countries like Pakistan, this sector is considered the backbone of the economy, and most of the economic decision making revolves around agricultural outputs and data. Timely and accurate facts and figures about this vital sector hold immense significance and have serious implications for the long-term development of the economy. Therefore, any significant improvements in the statistics and other forms of data regarding agriculture sector are considered important by all policymakers. This is especially true for decision making for the betterment of crops and the agriculture sector in general. Provincial and federal agricultural departments collect data for all cash and non-cash crops and the sector, in general, every year. Traditional data collection for such a large sector i.e. agriculture, being time-consuming, prone to human error and labor-intensive, is slowly but gradually being replaced by remote sensing techniques. For this study, remotely sensed data were used for change detection (machine learning, supervised & unsupervised classification) to assess the increase or decrease in area under agriculture over the last fifteen years due to urbanization. Detailed Landsat Images for the selected agricultural districts were acquired for the year 2000 and compared to images of the same area acquired for the year 2016. Observed differences validated through detailed analysis of the areas show that there was a considerable decrease in vegetation during the last fifteen years in four major agricultural districts of the Punjab province due to urbanization (housing societies).

Keywords: change detection, area estimation, machine learning, urbanization, remote sensing

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Authors: Muhammad Tayyab Afzal, Muhammad Arslan, Mirza Muhammad Waqar

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One of the key components of the water cycle is evapotranspiration (ET), which represents water consumption by vegetated and non-vegetated surfaces. Conventional techniques for measurements of ET are point based and representative of the local scale only. Satellite remote sensing data with large area coverage and high temporal frequency provide representative measurements of several relevant biophysical parameters required for estimation of ET at regional scales. The objective is of this research is to exploit satellite data in order to estimate evapotranspiration. This study uses Surface Energy Balance System (SEBS) model to calculate daily actual evapotranspiration (ETa) in Larkana District, Sindh Pakistan using Landsat TM data for clouds-free days. As there is no flux tower in the study area for direct measurement of latent heat flux or evapotranspiration and sensible heat flux, therefore, the model estimated values of ET were compared with reference evapotranspiration (ETo) computed by FAO-56 Penman Monteith Method using meteorological data. For a country like Pakistan, agriculture by irrigation in the river basins is the largest user of fresh water. For the better assessment and management of irrigation water requirement, the estimation of consumptive use of water for agriculture is very important because it is the main consumer of water. ET is yet an essential issue of water imbalance due to major loss of irrigation water and precipitation on cropland. As large amount of irrigated water is lost through ET, therefore its accurate estimation can be helpful for efficient management of irrigation water. Results of this study can be used to analyse surface conditions, i.e. temperature, energy budgets and relevant characteristics. Through this information we can monitor vegetation health and suitable agricultural conditions and can take controlling steps to increase agriculture production.

Keywords: SEBS, remote sensing, evapotranspiration, ETa

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Authors: Muhammad Asif Syed, Mirza Amir Baig

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Background: Pakistan is one of the two remaining polio-endemic countries, posing a significant public health challenge for global polio eradication due to failure to interrupt polio transmission. Country specific seroprevalence studies help in the evaluation of immunization program performance, the susceptibility of population against polio virus and identification of existing level of immunity with factors that affect seroconversion of the oral polio vaccine (OPV). The objective of the study was to find out factors associated with seroconversion of the OPV among children 6-59 months in Pakistan. Methods: A Hospital based cross-sectional serosurvey was undertaken in May-June 2015 at District Mirpurkhas, Sindh-Pakistan. Total 180 children aged 6–59 months were selected by using systematic random sampling from Muhammad Medical College Hospital, Mirpurkhas. Demographic, vaccination history and risk factors information were collected from the parents/guardian. Blood sample was collected and tested for the detection of poliovirus IgG antibodies by using ELISA Kit. The IgG titer <10 IU/ml, 50 to <150 IU/ml and >150 IU/ml was defined as negative, weak positive and positive immunity respectively. Pearson Chi-square test was used to determine the difference in seroprevalence in univariate analysis. Results: A total of 180 subjects were enrolled mean age was 23 months (7 -59 months). Off these 160 (89%) children were well and 18 (10%) partially protected against polio virus. Two (1.1%) children had no protection against polio virus as they had <10 IU/ml poliovirus IgG antibodies titer. Both negative cases belong from the female gender, age group 12-23 months, urban area and BMI <50 percentile. There was a difference between normal and the wasting children; it did attain statistical significance (χ2= 35.5, p=0.00). The difference in seroconversion was also observed in relation to the gender (χ2=6.23, p=0.04), duration of breast feeding (χ2=18.6, p=0.04), history of diarrheal disease before polio vaccine administration (χ2=7.7, p=0.02), and stunting (χ2= 114, p=0.00). Conclusion: This study demonstrated that near 90% children achieve seroconversion of OPV and well protected against polio virus. There is an urgent need to focus on factors like duration of breast feeding, diarrheal diseases and malnutrition (acute and chronic) among the children as an immunization strategy.

Keywords: seroconversion, oral polio vaccine, Polio, Pakistan

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Authors: Sameer A. Pathan, Biswadev Mitra, Salman Mirza, Umais Momin, Zahoor Ahmed, Lubna G. Andraous, Dharmesh Shukla, Mohammed Y. Shariff, Magid M. Makki, Tinsy T. George, Saad S. Khan, Stephen H. Thomas, Peter A. Cameron

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Study objective: Emergency physician’s (EP) ability to identify hydronephrosis on point-of-care ultrasound (POCUS) has been assessed in the past using CT scan as the reference standard. We aimed to assess EP interpretation of POCUS to identify and grade the hydronephrosis in a direct comparison with the consensus-interpretation of POCUS by radiologists, and also to compare the EP and radiologist performance using CT scan as the criterion standard. Methods: Using data from a POCUS databank, a prospective interpretation study was conducted at an urban academic emergency department. All POCUS exams were performed on patients presenting with renal colic to the ED. Institutional approval was obtained for conducting this study. All the analyses were performed using Stata MP 14.0 (Stata Corp, College Station, Texas). Results: A total of 651 patients were included, with paired sets of renal POCUS video clips and the CT scan performed at the same ED visit. Hydronephrosis was reported in 69.6% of POCUS exams by radiologists and 72.7% of CT scans (p=0.22). The κ for consensus interpretation of POCUS between the radiologists to detect hydronephrosis was 0.77 (0.72 to 0.82) and weighted κ for grading the hydronephrosis was 0.82 (0.72 to 0.90), interpreted as good to very good. Using CT scan findings as the criterion standard, Eps had an overall sensitivity of 81.1% (95% CI: 79.6% to 82.5%), specificity of 59.4% (95% CI: 56.4% to 62.5%), PPV of 84.3% (95% CI: 82.9% to 85.7%), and NPV of 53.8% (95% CI: 50.8% to 56.7%); compared to radiologist sensitivity of 85.0% (95% CI: 82.5% to 87.2%), specificity of 79.7% (95% CI: 75.1% to 83.7%), PPV of 91.8% (95% CI: 89.8% to 93.5%), and NPV of 66.5% (95% CI: 61.8% to 71.0%). Testing for a report of moderate or high degree of hydronephrosis, specificity of EP was 94.6% (95% CI: 93.7% to 95.4%) and to 99.2% (95% CI: 98.9% to 99.5%) for identifying severe hydronephrosis alone. Conclusion: EP POCUS interpretations were comparable to the radiologists for identifying moderate to severe hydronephrosis using CT scan results as the criterion standard. Among patients with moderate or high pre-test probability of ureteric calculi, as calculated by the STONE-score, the presence of moderate to severe (+LR 6.3 and –LR 0.69) or severe hydronephrosis (+LR 54.4 and –LR 0.57) was highly diagnostic of the stone disease. Low dose CT is indicated in such patients for evaluation of stone size and location.

Keywords: renal colic, point-of-care, ultrasound, bedside, emergency physician

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Authors: Urooj Saeed, Sajid Rashid Ahmad, Iqra Khalid, Sahar Mirza, Imtiaz Younas

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Pakistan, a flood-prone country, has experienced worst floods in the recent past which have caused extensive damage to the urban and rural areas by loss of lives, damage to infrastructure and agricultural fields. Poor flood management system in the country has projected the risks of damages as the increasing frequency and magnitude of floods are felt as a consequence of climate change; affecting national economy directly or indirectly. To combat the needs of flood emergency, this paper focuses on remotely sensed data based approach for rapid mapping and monitoring of flood extent and its damages so that fast dissemination of information can be done, from local to national level. In this research study, spatial extent of the flooding caused by heavy rains of 2014 has been mapped by using space borne data to assess the crop damages and affected population in sixteen districts of Punjab. For this purpose, moderate resolution imaging spectroradiometer (MODIS) was used to daily mark the flood extent by using Normalised Difference Water Index (NDWI). The highest flood value data was integrated with the LandScan 2014, 1km x 1km grid based population, to calculate the affected population in flood hazard zone. It was estimated that the floods covered an area of 16,870 square kilometers, with 3.0 million population affected. Moreover, to assess the flood damages, Object Based Image Analysis (OBIA) aided with spectral signatures was applied on Landsat image to attain the thematic layers of healthy (0.54 million acre) and damaged crops (0.43 million acre). The study yields that the population of Jhang district (28% of 2.5 million population) was affected the most. Whereas, in terms of crops, Jhang and Muzzafargarh are the ‘highest damaged’ ranked district of floods 2014 in Punjab. This study was completed within 24 hours of the peak flood time, and proves to be an effective methodology for rapid assessment of damages due to flood hazard

Keywords: flood hazard, space borne data, object based image analysis, rapid damage assessment

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Authors: M. Mirza Y. Harahap

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This paper explores the interiority of children’s territorialisation in domestic space context by looking at their affective relations with their surroundings. Examining its spatiality, the research focuses on the interactions that developed between the children and the things which exist in their house, specifically those which left traces, indicating the very arena of their territory. As early learners, the children whose mind and body are still in the development stage are hypothetically distinct in the way they territorialise the space. Rule, common sense and other form of common acceptances among the adults might not be relevant with their way on territorialising the space. Unpredictability-ness, inappropriateness, and unimaginableness hypothetically characterise their unique endeavour when territorialising the space. The purpose might even be insignificant, expressing their very development which unrestricted. This indicates how the interiority of children’s territorialisation in a domestic space context actually is. It would also implicate on a new way of seeing territory since territorialisation act has natural purpose: to aim the space and regard them as his/her own. Aiming to disclose the above territorialisation characteristics, this paper addresses a qualitative study which covers a comprehensive analysis as follow: 1) Collecting various territorial traces left from the children activities within their respective houses. Further within this stage, the data is categorised based on the territorial strategy and tactic. This stage would particularly result in the overall map of the children’s territorial interiority which expresses its focuses, range and ways; 2) Examining the interactions occurred between the children and the spatial elements within the house. Stressing on the affective relations, this stage revealed the immaterial aspect of the children’s territorialisation, thus disclosed the unseen spatial aspect of territorialisation; and 3) Synthesising the previous two stages. Correlating the results from the two stages would then help us to understand the children’s unpredictable, inappropriate and unimaginable territorial interiority. This would also help us to justify how the children learn the space through territorialisation act, its importance and its position in interiority conception. The discussed relation between the children and the houses that cover both its physical and imaginary entity as part of their overall dwelling space would also help us to have a better understanding towards specific spatial elements which are significant and undeniably important for children’s spatial learning process. Particularly for this last finding, it would also help us to determine what kind of spatial elements which are necessary to be existed in a house, thus help for design development purpose. Overall, the study in this paper would help us to broaden our mindset regarding the territory, dwelling, interiority and the overall interior architecture conception, promising a chance for further research within interior architecture field.

Keywords: children, interiority, relation, territory

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Authors: Misha Mirza

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In recent years, the definition of journalism in Pakistan has changed, so has the mindset of people and their approach towards a news story. For the audience, news has become more interesting than a drama or a film. This research thus provides an insight into Pakistan’s evolving media landscape. It tries not only to bring forth the outcomes of cross-platform cooperation among print and broadcast journalism but also gives an insight into the interactive data visualization techniques being used. The storytelling in journalism in Pakistan has evolved from depicting merely the truth to tweaking, fabricating and producing docu-dramas. It aims to look into how news is translated to a visual. Pakistan acquires a diverse cultural heritage and by engaging audience through media, this history translates into the storytelling platform today. The paper explains how journalists are thriving in a converging media environment and provides an analysis of the narratives in television talk shows today.’ Jack of all, master of none’ is being challenged by the journalists today. One has to be a quality information gatherer and an effective storyteller at the same time. Are journalists really looking more into what sells rather than what matters? Express Tribune is a very popular news platform among the youth. Not only is their newspaper more attractive than the competitors but also their style of narrative and interactive web stories lead to well-rounded news. Interviews are used as the basic methodology to get an insight into how data visualization is compassed. The quest for finding out the difference between visualization of information versus the visualization of knowledge has led the author to delve into the work of David McCandless in his book ‘Knowledge is beautiful’. Journalism in Pakistan has evolved from information to combining knowledge, infotainment and comedy. What is being criticized the most by the society most often becomes the breaking news. Circulation in today’s world is carried out in cultural and social networks. In recent times, we have come across many examples where people have gained overnight popularity by releasing songs with substandard lyrics or senseless videos perhaps because creativity has taken over information. This paper thus discusses the various platforms of convergence journalism from Pakistan’s perspective. The study concludes with proving how Pakistani pop culture Truck art is coexisting with all the platforms in convergent journalism. The changing media landscape thus challenges the basic rules of journalism. The slapstick humor and ‘jhatka’ in Pakistani talk shows has evolved from the Pakistani truck art poetry. Mobile journalism has taken over all the other mediums of journalism; however, the Pakistani culture coexists with the converging landscape.

Keywords: convergence journalism in Pakistan, data visualization, interactive narrative in Pakistani news, mobile journalism, Pakistan's truck art culture

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Authors: Shahzad A. Mughal, Ameer A. P. Ghaloo, Faisal Laghari, Mohsin A. Mirza

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Job satisfaction and level of job stressors among employees of a university are considered as essential factors responsible for institutional success. Job satisfaction is usually believed as a single baseline variable for the evaluation of a university human resource area. The objectives of this study were to assess the level of job satisfaction and influence of job stressors among university teachers and their association with long term physical health of the employees in government sector universities in Pakistan. A cross-sectional study was conducted on university employees including faculty members and administrative staff of three government sector universities in Sindh province of Pakistan who have completed at least ten years of their job. The study period was six months. All the employees were randomly selected. The job satisfaction scale Questionnaire with yes and no options, together with questions regarding demographic factors, job stress or other working factors and physical health issues were administered in questionnaires. These questionnaires were handed out to 100 faculty members of both genders with permanent job and 50 non faculty staff of grade 17 and above with permanent employment status. Students’ T test and one way ANOVA was applied to categorical variables and Pearson’s correlation analysis was performed to evaluate the correlations between study variables. 121 successful responses were obtained (effective respondent rate 80.6%). The average score of overall job satisfaction was 65.6%. Statistical analysis revealed that the job satisfaction and work related stressors had negative impact on overall health status of the employees with resultant less efficacy and mental stress. The positive relation was perceived by employees for organizational support and high income with job satisfaction. Demographic features such as age and female gender were also linked to the level of job satisfaction and health related issues. The total variation among all responses regarding correlation between job satisfaction job stressors and health related issues was 55%. A study was conducted on University employees of government sector Universities in Pakistan, regarding association of job satisfaction and job stressors with long term physical health of the employees. Study revealed a moderate level of job satisfaction among the employees of all universities included in this study. Attitude and personal relations with heads of the departments and institution along with salary packages were considered as biggest job stressors related correlated directly with physical health. Demographic features and gender were associated factors for job satisfaction. Organizational support was the strongest factor for job satisfaction and results pointed out that by improving support level from University may improve the quality of job satisfaction and overall health of employees.

Keywords: job satisfaction, organizational support, physical health, university employees

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Authors: Anjali Roy, Mirza S. Baig

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Atherosclerosis is a chronic inflammatory disease characterized by the formation of lipid rich plaque enriched with necrotic core, modified lipid accumulation, smooth muscle cells, endothelial cells, leucocytes and macrophages. Macrophage foam cells play a critical role in the occurrence and development of inflammatory atherosclerotic plaque. Foam cells are the fat-laden macrophages in the initial stage atherosclerotic lesion formation. Foam cells are an indication of plaque build-up, or atherosclerosis, which is commonly associated with increased risk of heart attack and stroke as a result of arterial narrowing and hardening. The mechanisms that drive atherosclerotic plaque progression remain largely unknown. Dissecting the molecular mechanism involved in process of macrophage foam cell formation will help to develop therapeutic interventions for atherosclerosis. To investigate the mechanism, we studied the role of nitric oxide synthase 1(NOS1)-mediated nitric oxide (NO) on low-density lipoprotein (LDL) uptake by bone marrow derived macrophages (BMDM). Using confocal microscopy, we found that incubation of macrophages with NOS1 inhibitor, TRIM (1-(2-Trifluoromethylphenyl) imidazole) or L-NAME (N omega-nitro-L-arginine methyl ester) prior to LDL treatment significantly reduces the LDL uptake by BMDM. Further, addition of NO donor (DEA NONOate) in NOS1 inhibitor treated macrophages recovers the LDL uptake. Our data strongly suggest that NOS1 derived NO regulates LDL uptake by macrophages and foam cell formation. Moreover, we also checked proinflammatory cytokine mRNA expression through real time PCR in BMDM treated with LDL and copper oxidized LDL (OxLDL) in presences and absences of inhibitor. Normal LDL does not evoke cytokine expression whereas OxLDL induced proinflammatory cytokine expression which significantly reduced in presences of NOS1 inhibitor. Rapid NOS-1-derived NO and its stable derivative formation act as signaling agents for inducible NOS-2 expression in endothelial cells, leading to endothelial vascular wall lining disruption and dysfunctioning. This study highlights the role of NOS1 as critical players of foam cell formation and would reveal much about the key molecular proteins involved in atherosclerosis. Thus, targeting NOS1 would be a useful strategy in reducing LDL uptake by macrophages at early stage of disease and hence dampening the atherosclerosis progression.

Keywords: atherosclerosis, NOS1, inflammation, oxidized LDL

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Authors: Shiva Naidoo, Kristena Yossef, Grimm Jimm, Mirza Wasique, Eric Kemmerer, Joshua Obuch, Anand Mahadevan

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Background: Fiducial markers effectively enhance tumor target visibility prior to Stereotactic Body Radiation Therapy or Proton therapy. To streamline clinical practice, fiducial placement guidelines from a robotic radiosurgery vendor were examined with the goals of optimizing and standardizing feasible geometries for each treatment indication. Clinical examples of prostate, renal, and pancreatic cases are presented. Methods: Vendor guidelines (Accuray, Sunnyvale, Ca) suggest implantation of 4–6 fiducials at least 20 mm apart, with at least a 15-degree angular difference between fiducials, within 50 mm or less from the target centroid, to ensure that any potential fiducial motion (e.g., from respiration or abdominal/pelvic pressures) will mimic target motion. Also recommended is that all fiducials can be seen in 45-degree oblique views with no overlap to coincide with the robotic radiosurgery imaging planes. For the prostate, a standardized geometry that meets all these objectives is a 2 cm-by-2 cm square in the coronal plane. The transperineal implant of two pairs of preloaded tandem fiducials makes the 2 cm-by-2 cm square geometry clinically feasible. This technique may be applied for renal cancer, except repositioned in a sagittal plane, with the retroperitoneal placement of the fiducials into the tumor. Pancreatic fiducial placement via endoscopic ultrasound (EUS) is technically more challenging, as fiducial placement is operator-dependent, and lesion access may be limited by adjacent vasculature, tumor location, or restricted mobility of the EUS probe in the duodenum. Fluoroscopically assisted fiducial placement during EUS can help ensure fiducial markers are deployed with optimal geometry and visualization. Results: Among the first 22 fiducial cases on a newly installed robotic radiosurgery system, live x-ray images for all nine prostatic cases had excellent fiducial visualization at the treatment console. Renal and pancreatic fiducials were not as clearly visible due to difficult target access and smaller caliber insertion needle/fiducial usage. The geometry of the first prostate case was used to ensure accurate geometric marker placement for the remaining 8 cases. Initially, some of the renal and pancreatic fiducials were closer than the 20 mm recommendation, and interactive feedback with the proceduralists led to subsequent fiducials being too far to the edge of the tumor. Further feedback and discussion of all cases are being used to help guide standardized geometries and achieve ideal fiducial placement. Conclusion: The ideal tradeoffs of fiducial visibility versus the thinnest possible gauge needle to avoid complications needs to be systematically optimized among all patients, particularly in regards to body habitus. Multidisciplinary collaboration among proceduralists and radiation oncologists can lead to improved outcomes.

Keywords: fiducial, prostate cancer, renal cancer, pancreatic cancer, radiotherapy

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