ECONOMIC EVALUATION OF BULGHAH MINE PROJECT GOLD DEPOSIT IN SAUDI ARABIA

This project is an outcome of the postgraduate diploma course on Project evaluation, CESPROMIN, for the year 2008-09, one of the CESMAT cycles in the frame of MINES ParisTech. The objective of this project was to understand the methods of Economic Evaluation of a Mining Project, which includes the selection of Mining method & Reserve estimation & Financial Assessment. To present my understanding on Mine Economics & impact of different parameters of Project Finance, as a part of Final report for the CESPROMIN Course, I have tried to do the Economic Evaluation of Bulghah North Gold Mine, which is still in conceptual stage. From the limited data available, I with the help of Dr. Isabelle Thenevin tried to run Whittle software to optimize the Pit but due to improper block model I could not succeed in optimizing the Pit. The reason for that is the project is still geological evaluation stage, under the consultant engaged for the purpose. The Project evaluation has been done in three options. Option I &II with stripping ratio 1.4 t/ m3 and option III with stripping ratio 1.7t/m3 at Cut-off grade 0.3 g/t. To improvement the final product recovery of the fresh ore I suggested to up date the plant by adding new tertiary crusher parallel with old tertiary crusher to reduce the particle size

A Real-World Study in Patients with Type 2 Diabetes Treated with Gliclazide Modified Release during Fasting in Gulf Cooperation Council Countries: An Analysis from the International DIA-RAMADAN Study

Introduction: The safety and effectiveness of gliclazide modified release (MR) in patients with type 2 diabetes mellitus (T2DM) who fasted during Ramadan were previously published. Here, we carried out a regional analysis among patients living in Gulf Cooperation Council (GCC) countries. Patients and Methods: DIA-RAMADAN was a real-world, observational, international, noncomparative study conducted in nine countries that included >1200 T2DM adults receiving gliclazide MR for at least 90 days before inclusion. The study comprised 2 visits: at inclusion, 6–8 weeks before the start of Ramadan (V0) and 4–6 weeks after the end of Ramadan (V1). The primary endpoint was the proportion of patients reporting ≥1 symptomatic hypoglycemic event as collected using a patient diary. Changes in HbA1c, fasting plasma glucose (FPG), and weight were also analyzed. This manuscript represents data collected in GCC countries (Kuwait, Saudi Arabia, and United Arab Emirates). Results: Data from 161 patients were analyzed: mean (SD) age 56.8 (10.6) years, 30.4% women, body mass index 29.1 (3.7) kg/m2, T2DM disease duration 6.7 (3.3) years, baseline HbA1c 7.9% (0.8). The proportions of patients reporting ≥1 symptomatic hypoglycemic event or confirmed hypoglycemia during Ramadan were 4.3% and 0.6%, respectively. No cases of severe hypoglycemia were reported. Significant reductions in main variables were observed before the start of Ramadan (V0) and 4–6 weeks after the end of Ramadan (V1): HbA1c (from 7.9 [0.8] to 7.6 [0.7]%; p value <0.001), FPG (from 143.5 [24.3] to 137.9 [25.2] mg/dL; p value = 0.031), and weight (from 79.0 [73.0–86.0] to 78.0 [72.0–85.0] kg; p value = 0.018). Conclusions: These real-world data indicate that patients with T2DM treated with gliclazide MR during Ramadan in the selected GCC countries have a low risk of hypoglycemia and maintain glycemic control and weight while fasting

Advancing therapy in suboptimally controlled basal insulin-treated type 2 diabetes:Clinical outcomes with iGlarLixi versus premix BIAsp 30 in the SoliMix randomized controlled trial

OBJECTIVE: To directly compare the efficacy and safety of a fixed-ratio combination, of insulin glargine 100 units/mL and the glucagon-like peptide 1 receptor agonist lixisenatide (iGlarLixi), with those of a premix insulin analog, biphasic aspart insulin 30 (30% insulin aspart and 70% insulin aspart protamine) (BIAsp 30) as treatment advancement in type 2 diabetes suboptimally controlled on basal insulin plus oral antihyperglycemic drugs (OADs). RESEARCH DESIGN AND METHODS: In SoliMix, a 26-week, open-label, multicenter study, adults with suboptimally controlled basal insulin–treated type 2 diabetes (HbA(1c) ≥7.5% and ≤10%) were randomized to once-daily iGlarLixi or twice-daily BIAsp 30. Primary efficacy end points were noninferiority in HbA(1c) reduction (margin 0.3%) or superiority in body weight change for iGlarLixi versus BIAsp 30. RESULTS: Both primary efficacy end points were met: after 26 weeks, baseline HbA(1c) (8.6%) was reduced by 1.3% with iGlarLixi and 1.1% with BIAsp 30, meeting noninferiority (least squares [LS] mean difference −0.2% [97.5% CI −0.4, −0.1]; P < 0.001). iGlarLixi was also superior to BIAsp 30 for body weight change (LS mean difference −1.9 kg [95% CI −2.3, −1.4]) and percentage of participants achieving HbA(1c) <7% without weight gain and HbA(1c) <7% without weight gain and without hypoglycemia (all P < 0.001). iGlarLixi was also superior versus BIAsp 30 for HbA(1c) reduction (P < 0.001). Incidence and rates of American Diabetes Association level 1 and 2 hypoglycemia were lower with iGlarLixi versus BIAsp 30. CONCLUSIONS: Once-daily iGlarLixi provided better glycemic control with weight benefit and less hypoglycemia than twice-daily premix BIAsp 30. iGlarLixi is a more efficacious, simpler, and well-tolerated alternative to premix BIAsp 30 in suboptimally controlled type 2 diabetes requiring treatment beyond basal insulin plus OAD therapy. VIDEO 1: [Figure: see text] [Figure: see text

A Two-Gene Balance Regulates Salmonella Typhimurium Tolerance in the Nematode Caenorhabditis elegans

Lysozymes are antimicrobial enzymes that perform a critical role in resisting infection in a wide-range of eukaryotes. However, using the nematode Caenorhabditis elegans as a model host we now demonstrate that deletion of the protist type lysozyme LYS-7 renders animals susceptible to killing by the fatal fungal human pathogen Cryptococcus neoformans, but, remarkably, enhances tolerance to the enteric bacteria Salmonella Typhimurium. This trade-off in immunological susceptibility in C. elegans is further mediated by the reciprocal activity of lys-7 and the tyrosine kinase abl-1. Together this implies a greater complexity in C. elegans innate immune function than previously thought

Phenotypic covariance of longevity, immunity and stress resistance in the Caenorhabditis nematodes

Background \ud Ageing, immunity and stresstolerance are inherent characteristics of all organisms. In animals, these traits are regulated, at least in part, by forkhead transcription factors in response to upstream signals from the Insulin/Insulin– like growth factor signalling (IIS) pathway. In the nematode Caenorhabditis elegans, these phenotypes are molecularly linked such that activation of the forkhead transcription factor DAF-16 both extends lifespan and simultaneously increases immunity and stress resistance. It is known that lifespan varies significantly among the Caenorhabditis species but, although DAF-16 signalling is highly conserved, it is unclear whether this phenotypic linkage occurs in other species. Here we investigate this phenotypic covariance by comparing longevity, stress resistance and immunity in four \ud Caenorhabditis species. \ud \ud Methodology/Principal Findings \ud We show using phenotypic analysis of DAF-16 influenced phenotypes that among four closely related Caenorhabditis nematodes, the gonochoristic species (Caenorhabditis remanei and Caenorhabditis brenneri) have diverged \ud significantly with a longer lifespan, improved stress resistance and higher immunity than the hermaphroditic species (C. elegans and Caenorhabditis briggsae). Interestingly, we also observe significant differences in expression levels between the daf-16 homologues in these species using Real-Time PCR, which positively correlate with the observed phenotypes. Finally, we provide additional evidence in support of a role for DAF-16 in regulating phenotypic coupling by using a combination of wildtype isolates, constitutively active daf-16 mutants and bioinformatic analysis. \ud \ud Conclusions \ud The gonochoristic species display a significantly longer lifespan (p < 0.0001)and more robust immune and stress response (p<0.0001, thermal stress; p<0.01, heavy metal stress; p<0.0001, pathogenic stress) than the hermaphroditic species. Our data suggests that divergence in DAF-16 mediated phenotypes may underlie many of the differences observed between these four species of Caenorhabditis nematodes. These findings are further supported by the correlative higher daf-16 expression levels among the gonochoristic species and significantly higher lifespan, immunity and stress tolerance in the constitutively active daf-16 hermaphroditic mutants

Phenotypic covariance of Longevity, Immunity and Stress Resistance in the Caenorhabditis Nematodes

Background: Ageing, immunity and stresstolerance are inherent characteristics of all organisms. In animals, these traits are regulated, at least in part, by forkhead transcription factors in response to upstream signals from the Insulin/Insulin–like growth factor signalling (IIS) pathway. In the nematode Caenorhabditis elegans, these phenotypes are molecularly linked such that activation of the forkhead transcription factor DAF-16 both extends lifespan and simultaneously increases immunity and stress resistance. It is known that lifespan varies significantly among the Caenorhabditis species but, although DAF-16 signalling is highly conserved, it is unclear whether this phenotypic linkage occurs in other species. Here we investigate this phenotypic covariance by comparing longevity, stress resistance and immunity in four Caenorhabditis species. \ud \ud Methodology/Principal Findings: We show using phenotypic analysis of DAF-16 influenced phenotypes that among four closely related Caenorhabditis nematodes, the gonochoristic species (Caenorhabditis remanei and Caenorhabditis brenneri) have diverged significantly with a longer lifespan, improved stress resistance and higher immunity than the hermaphroditic species (C. elegans and Caenorhabditis briggsae). Interestingly, we also observe significant differences in expression levels between the daf-16 homologues in these species using Real-Time PCR, which positively correlate with the observed phenotypes. Finally, we provide additional evidence in support of a role for DAF-16 in regulating phenotypic coupling by using a combination of wildtype isolates, constitutively active daf-16 mutants and bioinformatic analysis. \ud \ud Conclusions: The gonochoristic species display a significantly longer lifespan (p<0.0001) and more robust immune and stress response (p<0.0001, thermal stress; p<0.01, heavy metal stress; p<0.0001, pathogenic stress) than the hermaphroditic species. Our data suggests that divergence in DAF-16 mediated phenotypes may underlie many of the differences observed between these four species of Caenorhabditis nematodes. These findings are further supported by the correlative higher daf-16 expression levels among the gonochoristic species and significantly higher lifespan, immunity and stress tolerance in the constitutively active daf-16 hermaphroditic mutants

A Role for the RNA Chaperone Hfq in Controlling Adherent-Invasive Escherichia coli Colonization and Virulence

Adherent-invasive Escherichia coli (AIEC) has been linked with the onset and perpetuation of inflammatory bowel diseases. The AIEC strain LF82 was originally isolated from an ileal biopsy from a patient with Crohn's disease. The pathogenesis of LF82 results from its abnormal adherence to and subsequent invasion of the intestinal epithelium coupled with its ability to survive phagocytosis by macrophages once it has crossed the intestinal barrier. To gain further insight into AIEC pathogenesis we employed the nematode Caenorhabditis elegans as an in vivo infection model. We demonstrate that AIEC strain LF82 forms a persistent infection in C. elegans, thereby reducing the host lifespan significantly. This host killing phenotype was associated with massive bacterial colonization of the nematode intestine and damage to the intestinal epithelial surface. C. elegans killing was independent of known LF82 virulence determinants but was abolished by deletion of the LF82 hfq gene, which encodes an RNA chaperone involved in mediating posttranscriptional gene regulation by small non-coding RNAs. This finding reveals that important aspects of LF82 pathogenesis are controlled at the posttranscriptional level by riboregulation. The role of Hfq in LF82 virulence was independent of its function in regulating RpoS and RpoE activity. Further, LF82Δhfq mutants were non-motile, impaired in cell invasion and highly sensitive to various chemical stress conditions, reinforcing the multifaceted function of Hfq in mediating bacterial adaptation. This study highlights the usefulness of simple non-mammalian infection systems for the identification and analysis of bacterial virulence factors