235 research outputs found

    Contributing Factors of Time Overrun in Public Sector Construction Projects

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    Time overrun is a major issue in construction projects. Its causes vary, depending upon the nature and size of the project. Developing countries are more susceptible to this problem due to limited resources and lack of managerial skills. This paper focuses on the identification and classification of time overrun factors in public sector projects in Pakistan. Data was collected by the use of a questionnaire given to different professionals in the construction field. Average index (AI) was used to determine each factor’s relative importance. Results indicate that financial difficulties faced by constructor, inadequate planning and scheduling, financial difficulties faced by client, delays in payment by the client, delays in decision making by the client, design mistakes, frequent design changes, material shortage, incompetent sub-constructor assigned by the constructor, poor site management and supervision and inadequate constructor’s experience are the most significant factors of time overrun in public sector construction projects in Pakistan. This study aims to be useful in addressing the issue of time overrun in the construction industry

    A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease

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    Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association studies (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of 185 thousand CAD cases and controls, interrogating 6.7 million common (MAF>0.05) as well as 2.7 million low frequency (0.005<MAF<0.05) variants. In addition to confirmation of most known CAD loci, we identified 10 novel loci, eight additive and two recessive, that contain candidate genes that newly implicate biological processes in vessel walls. We observed intra-locus allelic heterogeneity but little evidence of low frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect siz

    An unbiased lipid phenotyping approach to study the genetic determinants of lipids and their association with coronary heart disease risk factors

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    Direct infusion high-resolution mass spectrometry (DIHRMS) is a novel, high-throughput approach to rapidly and accurately profile hundreds of lipids in human serum without prior chromatography, facilitating in-depth lipid phenotyping for large epidemiological studies to reveal the detailed associations of individual lipids with coronary heart disease (CHD) risk factors. Intact lipid profiling by DIHRMS was performed on 5662 serum samples from healthy participants in the Pakistan Risk of Myocardial Infarction Study (PROMIS). We developed a novel semi-targeted peak-picking algorithm to detect mass-to-charge ratios in positive and negative ionization modes. We analyzed lipid partial correlations, assessed the association of lipid principal components with established CHD risk factors and genetic variants, and examined differences between lipids for a common genetic polymorphism. The DIHRMS method provided information on 360 lipids (including fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, and sterol lipids), with a median coefficient of variation of 11.6% (range: 5.4–51.9). The lipids were highly correlated and exhibited a range of associations with clinical chemistry biomarkers and lifestyle factors. This platform can provide many novel insights into the effects of physiology and lifestyle on lipid metabolism, genetic determinants of lipids, and the relationship between individual lipids and CHD risk factors

    Strategies in a metallophyte species to cope with manganese excess

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    The effect of exposure to high Mn concentration was studied in a metallophyte species, Erica andevalensis, using hydroponic cultures with a range of Mn concentrations (0.06, 100, 300, 500, and 700 mg L-1). At harvest, biomass production, element uptake, and biochemical indicators of metal stress (leaf pigments, organic acids, amino acids, phenols, and activities of catalase, peroxidase, superoxide dismutase) were determined in leaves and roots. Increasing Mn concentrations led to a decrease in biomass accumulation, and tip leaves chlorosis was the only toxicity symptom detected. In a similar way, photosynthetic pigments (chlorophylls a and b, and carotenoids) were affected by high Mn levels. Among organic acids, malate and oxalate contents in roots showed a significant increase at the highest Mn concentration, while in leaves, Mn led to an increasing trend in citrate and malate contents. An increase of Mn also induced an increase in superoxide dismutase activity in roots and catalase activity in leaves. As well, significant changes in free amino acids were induced by Mn concentrations higher than 300 mg L-1, especially in roots. No significant changes in phenolic compounds were observed in the leaves, but root phenolics were significantly increased by increasing Mn concentrations in treatments. When Fe supply was increased 10 and 20 times (7–14 mg Fe L-1 as Fe-EDDHA) in the nutrient solutions at the highest Mn concentration (700 mg Mn L-1), it led to significant increases in photosynthetic pigments and biomass accumulation. Manganese was mostly accumulated in the roots, and the species was essentially a Mn excluder. However, considering the high leaf Mn concentration recorded without toxicity symptoms, E. andevalensis might be rated as a Mn-tolerant speciesinfo:eu-repo/semantics/publishedVersio

    BMI, Diet and Female Reproductive Factors as Risks for Thyroid Cancer: A Systematic Review

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    Background: Thyroid cancer incidence rates have been increasing worldwide but the reason behind this is unclear. Both the increasing use of diagnostic technologies allowing the detection of thyroid cancer and a true increase in thyroid cancer incidence have been proposed. This review assesses the role of body mass index (BMI), diet, and reproductive factors on the thyroid cancer trend. Methods: Epidemiologic studies of the selected risk factors up to June 2010 were reviewed and critically assessed. Results: Among the thirty-seven studies reviewed and despite variation in the risk estimates, most papers supported a small but positive association for BMI (risk estimate range: 1.1–2.3 in males and 1.0–7.4 in females.). Among specific dietary components, there was no consistent association of thyroid cancer risk with iodine intake through fortification (risk estimate range: 0.49–1.6) or fish consumption (risk estimate range 0.6–2.2), nor with diets high in cruciferous vegetables (risk estimate range 0.6–1.9). A small number of studies showed a consistent protective effect of diets high in non-cruciferous vegetable (risk estimate range: 0.71–0.92). Among reproductive factors (pregnancy, parity, number of live births, use of prescription hormones, menstrual cycle regularity, and menopausal status), none were consistently associated with higher thyroid cancer risk. Conclusions: BMI had the strongest link to thyroid cancer risk among those examined. Detailed examinations of populationleve

    Glucocorticoids in T cell apoptosis and function

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    Glucocorticoids (GCs) are a class of steroid hormones which regulate a variety of essential biological functions. The profound anti-inflammatory and immunosuppressive activity of synthetic GCs, combined with their power to induce lymphocyte apoptosis place them among the most commonly prescribed drugs worldwide. Endogenous GCs also exert a wide range of immunomodulatory activities, including the control of T cell homeostasis. Most, if not all of these effects are mediated through the glucocorticoid receptor, a member of the nuclear receptor superfamily. However, the signaling pathways and their cell type specificity remain poorly defined. In this review, we summarize our present knowledge on GC action, the mechanisms employed to induce apoptosis and the currently discussed models of how they may participate in thymocyte development. Although our knowledge in this field has substantially increased during recent years, we are still far from a comprehensive picture of the role that GCs play in T lymphocytes

    Genomic profiling distinguishes familial multiple and sporadic multiple meningiomas

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    <p>Abstract</p> <p>Background</p> <p>Meningiomas may occur either as familial tumors in two distinct disorders, familial multiple meningioma and neurofibromatosis 2 (NF2), or sporadically, as either single or multiple tumors in individuals with no family history. Meningiomas in NF2 and approximately 60% of sporadic meningiomas involve inactivation of the <it>NF2 </it>locus, encoding the tumor suppressor merlin on chromosome 22q. This study was undertaken to establish whether genomic profiling could distinguish familial multiple meningiomas from sporadic solitary and sporadic multiple meningiomas.</p> <p>Methods</p> <p>We compared 73 meningiomas presenting as sporadic solitary (64), sporadic multiple (5) and familial multiple (4) tumors using genomic profiling by array comparative genomic hybridization (array CGH).</p> <p>Results</p> <p>Sporadic solitary meningiomas revealed genomic rearrangements consistent with at least two mechanisms of tumor initiation, as unsupervised cluster analysis readily distinguished tumors with chromosome 22 deletion (associated with loss of the <it>NF2 </it>tumor suppressor) from those without chromosome 22 deletion. Whereas sporadic meningiomas without chromosome 22 loss exhibited fewer chromosomal imbalance events overall, tumors with chromosome 22 deletion further clustered into two major groups that largely, though not perfectly, matched with their benign (WHO Grade I) or advanced (WHO Grades II and III) histological grade, with the latter exhibiting a significantly greater degree of genomic imbalance (P < 0.001). Sporadic multiple meningiomas showed a frequency of genomic imbalance events comparable to the atypical grade solitary tumors. By contrast, familial multiple meningiomas displayed no imbalances, supporting a distinct mechanism for the origin for these tumors.</p> <p>Conclusion</p> <p>Genomic profiling can provide an unbiased adjunct to traditional meningioma classification and provides a basis for exploring the different genetic underpinnings of tumor initiation and progression. Most importantly, the striking difference observed between sporadic and familial multiple meningiomas indicates that genomic profiling can provide valuable information for differential diagnosis of subjects with multiple meningiomas and for considering the risk for tumor occurrence in their family members.</p

    Prevalence and etiology of community-acquired pneumonia in immunocompromised patients

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    Background. The correct management of immunocompromised patients with pneumonia is debated. We evaluated the prevalence, risk factors, and characteristics of immunocompromised patients coming from the community with pneumonia. Methods. We conducted a secondary analysis of an international, multicenter study enrolling adult patients coming from the community with pneumonia and hospitalized in 222 hospitals in 54 countries worldwide. Risk factors for immunocompromise included AIDS, aplastic anemia, asplenia, hematological cancer, chemotherapy, neutropenia, biological drug use, lung transplantation, chronic steroid use, and solid tumor. Results. At least 1 risk factor for immunocompromise was recorded in 18% of the 3702 patients enrolled. The prevalences of risk factors significantly differed across continents and countries, with chronic steroid use (45%), hematological cancer (25%), and chemotherapy (22%) the most common. Among immunocompromised patients, community-acquired pneumonia (CAP) pathogens were the most frequently identified, and prevalences did not differ from those in immunocompetent patients. Risk factors for immunocompromise were independently associated with neither Pseudomonas aeruginosa nor non\u2013community-acquired bacteria. Specific risk factors were independently associated with fungal infections (odds ratio for AIDS and hematological cancer, 15.10 and 4.65, respectively; both P = .001), mycobacterial infections (AIDS; P = .006), and viral infections other than influenza (hematological cancer, 5.49; P < .001). Conclusions. Our findings could be considered by clinicians in prescribing empiric antibiotic therapy for CAP in immunocompromised patients. Patients with AIDS and hematological cancer admitted with CAP may have higher prevalences of fungi, mycobacteria, and noninfluenza viruses
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