|Commenced in January 2007||Frequency: Monthly||Edition: International||Paper Count: 16|
Background: Inter-individual variation in response to metformin, which has been considered as a first line therapy for T2DM treatment is considerable. In the current study, it was aimed to investigate the impact of two genetic variants Leu125Phe (rs77474263) and Gly64Asp (rs77630697) in gene SLC47A1 on the clinical efficacy of metformin in T2DM Pakistani patients. Methods: The study included 800 T2DM patients (400 metformin responders and 400 metformin non-responders) along with 400 ethnically matched healthy individuals. The genotypes were determined by allele-specific polymerase chain reaction. In-silico analysis was done to confirm the effect of the two SNPs on the structure of genes. Association was statistically determined using SPSS software. Results: Minor allele frequency for rs77474263 and rs77630697 was 0.13 and 0.12. For SLC47A1 rs77474263 the homozygotes of one mutant allele ‘T’ (CT) of rs77474263 variant were fewer in metformin responders than metformin non-responders (29.2% vs. 35.5 %). Likewise, the efficacy was further reduced (7.2% vs. 4.0 %) in homozygotes of two copies of ‘T’ allele (TT). Remarkably, T2DM cases with two copies of allele ‘C’ (CC) had 2.11 times more probability to respond towards metformin monotherapy. For SLC47A1 rs77630697 the homozygotes of one mutant allele ‘A’ (GA) of rs77630697 variant were fewer in metformin responders than metformin non-responders (33.5% vs. 43.0 %). Likewise, the efficacy was further reduced (8.5% vs. 4.5%) in homozygotes of two copies of ‘A’ allele (AA). Remarkably, T2DM cases with two copies of allele ‘G’ (GG) had 2.41 times more probability to respond towards metformin monotherapy. In-silico analysis revealed that these two variants affect the structure and stability of their corresponding proteins. Conclusion: The present data suggest that SLC47A1 Leu125Phe (rs77474263) and Gly64Asp (rs77630697) polymorphisms were associated with the therapeutic response of metformin in T2DM patients of Pakistan.
No state can be progressive and prosperous in which a large number of people is deprived of their basic economic rights and freedoms. In the contemporary world of globalization, the right to development has gained a momentum force in the domain of International Development Law (IDL) and has integrated into the National Legal System (NLS) of the major developed states. The international experts on human rights argued that the right to development (RTD) is called a third-generation human right which tends to enhance the welfare and prosperity of individuals, and thus, it is a right to a process whose outcomes are human rights despite the controversy on the implications of RTD. In the Pakistan legal system, the RTD has not been expressly stated in the constitution of the Islamic Republic of Pakistan, 1973. However, there are some implied constitutional provisions which reflect the concept of RTD. The jurisprudence on RTD is still an evolving paradigm in the contextual perspective of Pakistan, and the superior court of diverse jurisdiction acts as a catalyst regarding the protection and enforcement of RTD in the interest of the public at large. However, the case law explores the positive inclination of the courts in Pakistan on RTD be incorporated as an express provision in the chapters of fundamental rights; in this scenario, the high court’s of Pakistan under Article 199 and the supreme court of Pakistan under Article 184(3) have exercised jurisdiction on the enforcement of RTD. This paper inter-alia examines the national dimensions of RTD from the standpoint of state practice in Pakistan and it analyzes the experience of judiciary in the protection and enforcement of RTD. Moreover, the paper highlights the social and cultural challenges to Pakistan in the implementation of RTD and possible solution to improve the conditions of human rights in Pakistan. This paper will also highlight the steps taken by Pakistan regarding the awareness, incorporation, and propagation of RTD at the national level.
Construction industry plays a significant role in fulfilling the major requirements of the human being. It is one of the major constituents of every developed country. Although the construction industry of both the developing and developed countries encompasses a major part of the economy, and millions of rupees are utilized every year on various kinds of construction projects. But, this industry is facing numerous hurdles in terms of its budget and timely completion. Construction projects generally consist of several phases like planning, designing, execution, and finishing. This research study aims to determine the significant factors of time overrun in pre-construction planning (PCP) phase of construction projects in Pakistan. Questionnaires were distributed by various means and responses of respondents were compiled and collected data were then analyzed through a statistical technique using SPSS version 24. Major causes of time overrun in pre-construction planning phase; which is an extremely important phase of construction projects, were revealed. The research conclusion will provide a pathway for stakeholders to pay attention to the mentioned causes to overcome the major issue of time overrun.
A major goal in animal genetics is to understand the role of common genetic variants in diseases susceptibility and production traits. Sahiwal cattle can be considered as a global animal genetic resource due to its relatively high milk producing ability, resistance against tropical diseases and heat tolerant. CYP11B1 gene provides instructions for making a mitochondrial enzyme called steroid 11-beta-hydroxylase. It catalyzes the 11deoxy-cortisol to cortisol and 11deoxycorticosterone to corticosterone in cattle. The bovine CYP11B1 gene is positioned on BTA14q12 comprises of eight introns and nine exons and protein is associated with mitochondrial epithelium. The present study was aimed to identify the single-nucleotide polymorphisms in CYP11B1 gene in Sahiwal cattle breed of Pakistan. Four polymorphic sites were identified in exon one of CYP11B1 gene through sequencing approach. Significant finding was the incidence of the C→T polymorphism in 5'-UTR, causing amino acid substitution from alanine to valine (A30V) in Sahiwal cattle breed. That Ala/Val polymorphism may serve as a powerful genetic tool for the development of DNA markers that can be used for the particular traits for different local cattle breeds.
A cross-sectional study was carried out to determine the prevalence, species characterization and associated risk factors with Eimeria (E.) in sheep of district Toba Tek Singh from April, 2009 to March, 2010. Of the total 486 faecal samples examined for Eimeria, 209 (43%) were found infected with five species of Eimeria. Amongst the identified species of Eimeria, E. ovinoidalis was the commonest one (48.32%), followed in order by E. ahsata, E. intricata, E. parva and E. faurei with prevalence of 45.45, 28.71, 24.40 and 19.14 percent respectively. Peak prevalence was observed in August. Wet season (rainy and post-rainy) was found to be favourable for Eimeria infection. Lambs had significantly higher prevalence (P < 0.05) of Eimeria than adults. Similarly higher prevalence of Eimeria was observed in female as compared to male. Among management and husbandry practices; watering system, housing system, floor type and herd size strongly influenced the prevalence of Eimeria. Coccidiosis was more prevalent in closed housing system, non-cemented floor type, pond watered animals and larger herds (P < 0.05) as compared to open housing system, partially cemented floor type, tap watered animals and smaller herds respectively. Feeding system, breed and body condition of animals were not found as risk factors (P>0.05) influencing prevalence of Eimeria.
This study employs auto-regressive distributed lag (ARDL) bounds approach to cointegration for long run and errorcorrection modeling (ECM) for short run analysis to examine the relationship between revenue gap and economic growth for Pakistan using annual time series data over the period 1980 to 2008. The short and long run results indicate that revenue gap is statistical significant and negatively effect economic growth. The significant and negative coefficient of error correction term in ECM indicates that after a shock, the long rum equilibrium will again converge towards equilibrium about 10.406 percent within a year.
The objective of this study is to examine the validity of Wagner-s law and relationship between economic growth, population and export for Pakistan. The ARDL Bounds cointegration and ECM are utilized for long and short run equilibrium for the period of 1972-2007. Population has considerable role in an economy and exports are the main source to raise the GDP. With the increase in GDP, the government expenditures may or may not increase. The empirical results indicate that the Wagner-s Law does hold, as economic growth is significantly and positively correlated with government expenditures. However, population and exports have also significant and positive impact on government expenditures both in short and long run. The significant and negative coefficient of error correction term in ECM indicates that after a shock, the long rum equilibrium will again converge towards equilibrium about 70.82 percent within a year.
The preparation of good-quality Environmental Impact Assessment (EIA) reports contribute to enhancing overall effectiveness of EIA. This component of the EIA process becomes more important in situation where public participation is weak and there is lack of expertise on the part of the competent authority. In Pakistan, EIA became mandatory for every project likely to cause adverse environmental impacts from July 1994. The competent authority also formulated guidelines for preparation and review of EIA reports in 1997. However, EIA is yet to prove as a successful decision support tool to help in environmental protection. One of the several reasons of this ineffectiveness is the generally poor quality of EIA reports. This paper critically reviews EIA reports of some randomly selected projects. Interviews of EIA consultants, project proponents and concerned government officials have also been conducted to underpin the root causes of poor quality of EIA reports. The analysis reveals several inadequacies particularly in areas relating to identification, evaluation and mitigation of key impacts and consideration of alternatives. The paper identifies some opportunities and suggests measures for improving the quality of EIA reports and hence making EIA an effective tool to help in environmental protection.