LUCRATIVENESS OF ISLAMIC VS CONVENTIONAL MUTUAL FUNDS IN PAKISTAN

The purpose of this study is to conduct a comparative riskadjusted performance, selectivity skills and market timing abilitiesanalysis of Islamic and Conventional mutual funds in Pakistan. Thestudy utilizes various risk-adjusted performance measures to evaluaterisk and return characteristics. The study also used techniqueproposed by (Treynor and Mazuy 1966) and (Henriksson and Merton1981) to appraise selectivity skills and timing abilities on the dataset ranging 2009-2013 of Islamic and Conventional mutual funds. Inthis study, four categories Aggressive Fixed Income, Asset Allocation,Equity and Balanced open end mutual funds are analysed. On thebasis of evidences found, only few mutual fund managers from Islamicand Conventional mutual funds hold better stock picking skills. Themutual fund managers of both Islamic and conventional mutual fundsare found to be a poor market timer in Pakistan. Islamic mutualfunds have earned better returns than conventional mutual funds.Therefore, risk adjusted performance of Islamic mutual funds is betterthan conventional mutual funds

Single nucleotide polymorphisms in microRNA binding sites on the <i>HOX</i> genes regulate carcinogenesis:An <i>in-silico</i> approach

Homeobox proteins, encoded by HOX genes, are transcriptional factors playing a crucial role in the master regulatory pathway in the cells. Any mutations in HOX genes will affect the expression of its allied proteins. Such mutations were correlated to the development of different cancer types. In this study, we found 15 HOX genes with a potential target to miRNA, which regulates the translation of the protein by binding to its mRNA through the 3′UTR region. Single nucleotide polymorphisms (SNPs) in this binding region could drastically affect the protein expression by affecting the number and the stability of miRNA-mRNA complexes. We found 77 miRNAs in 15 genes which were found to have altered binding efficiency because of 26 SNPs. After which, we tried to evaluate the impact of each of these SNPs on related HOX genes. Some SNPs such as SNP 15689 on the HOXB7 gene will decrease gene expression by creating or enhancing new binding sites for miRNA to mRNA, while other SNPs such as SNP 872760 on the HOXB5 gene will overexpress the gene by breaking or decreasing existing binding sites from miRNA to mRNA. Then we conducted an expression analysis to compare the mRNA expression profiles in normal and cancer tissue. Subsequently, we did an enrichment analysis followed by a network analysis to shed light on the metabolic function of the gene that could be affected by mutation and whether these mutations may affect other genes. For the first time, this study delivers information on the possible epigenetic regulation of HOX genes via the 77 miRNAs that have predicted target binding sites on HOX mRNAs, and SNPs may regulate those. Furthermore, we show that the HOX gene misregulation may influence other HOX and non-HOX genes, based on network analysis.</p

Frequency and predictors of recurrence of bladder tumour on first check cystoscopy - a tertiary care hospital experience

Abstract OBJECTIVE: To determine the frequency and predictors of non-muscle invasive bladder tumour recurrence on first-check cystoscopy after transurethral resection of bladder tumour. METHODS: This cross-sectional study was conducted at the Aga Khan University Hospital, Karachi, from April to November 2014, and comprised patients with a suspected newly-diagnosed urothelial cancer. Patients with non-muscle invasive disease with complete resection of all visible lesions along with deep biopsy from the tumour base were included. Patients received standard adjuvant intravesical therapy according to their risk stratification and underwent a white-light check cystoscopy at 3 months to look for tumour recurrence. Association between clinico-pathological variables and recurrence at first cystoscopy was determined. SPSS 20 was used for data analysis. RESULTS: The mean age of 84 patients at presentation was 63.3±12.5 years (range: 36-89 years). There were 75(89%) men and 9(11%) women. On initial transurethral resection, the size of tumour was less than 3cm in 32(38%) participants and equal to or above 3cm in 52(62%). Single tumour was found in 51(61%) subjects and multiple tumours in 33(39%). None of the resected tumours was primary carcinoma in situ and 35(42%) tumours were of high grade. The overall recurrence rate at first cystoscopy was 28(33.3%). Larger tumour, higher grade and tumour multifocality were factors associated with recurrence at check cystoscopy (p\u3c0.05 each). Patients\\u27 age, gender, smoking status and tumour stage did not correlate with early recurrence (p\u3e0.05 each). CONCLUSIONS: The number, size and grade of the tumour strongly correlated with recurrence at check cystoscopy

Pecking at Pecking Order Theory: Evidence from Pakistan’s Non-financial Sector

This study tests the Pecking Order Theory for the capital structure of listed firms in Pakistan. As per Pecking Order Theory in capital structure formulation, internally generated resources would have first priority, followed by debt issuance where equity is used as a last resort. In its strong form, the Pecking Order Theory sustains that equity issues would never occur, whereas in its weak form, limited amounts of issues are acceptable. The methodology adopted in this empirical study involves cross-section regressions and the testing of hypotheses stemming from the underlying theory in its strong and weak forms. A sample of capital structure of non-financial firms listed at KSE is considered from 2001 to 2008. A statistical tool of panel data regression analysis is used to test different firms’ data. The value of R2, t-test and F-Stat indicate firms in KSE supporting the weak form of pecking order theory, i.e., the option of using internal equity and debt is more preferred and a limited amount of external equity is used for reinvestment and fund raising purposes

Ins and outs of cadmium-induced carcinogenesis:Mechanism and prevention

Cadmium (Cd) is a heavy metal and a highly toxic pollutant that is released into the environment as a byproduct of most modern factories and industries. Cd enters our body in significant quantities from contaminated water, cigarette smoke, or food product to many detrimental health hazards. Based on causal association all the Cd-related or derived compounds have been classified as carcinogens. In this study, we present an overview of the published literature to understand the molecular mechanisms for Cd-induced carcinogenesis and its prevention. In acute Cd poisoning production of reactive oxygen species is a key factor. However, chronic Cd exposure can transform cells to become more resistant to oxidative stress. Also, as an epigenetic mechanism Cd acts indirectly on DNA repair mechanisms via alteration of reactions upstream. Those transformed cells acquire resistance to apoptosis and deregulation of calcium homeostasis. Leading to uncontrolled carcinogenic cell proliferation and inherent DNA lesions. Flavonoids commonly found in plant foods have been shown to have a protective effect against Cd-induced carcinogenicity. A wide variety of tumorigenic mechanisms involved in chronic Cd exposure and the beneficial effects of flavonoids against Cd-induced carcinogenicity necessitate further investigations.</p

Ins and outs of cadmium-induced carcinogenesis:Mechanism and prevention

Cadmium (Cd) is a heavy metal and a highly toxic pollutant that is released into the environment as a byproduct of most modern factories and industries. Cd enters our body in significant quantities from contaminated water, cigarette smoke, or food product to many detrimental health hazards. Based on causal association all the Cd-related or derived compounds have been classified as carcinogens. In this study, we present an overview of the published literature to understand the molecular mechanisms for Cd-induced carcinogenesis and its prevention. In acute Cd poisoning production of reactive oxygen species is a key factor. However, chronic Cd exposure can transform cells to become more resistant to oxidative stress. Also, as an epigenetic mechanism Cd acts indirectly on DNA repair mechanisms via alteration of reactions upstream. Those transformed cells acquire resistance to apoptosis and deregulation of calcium homeostasis. Leading to uncontrolled carcinogenic cell proliferation and inherent DNA lesions. Flavonoids commonly found in plant foods have been shown to have a protective effect against Cd-induced carcinogenicity. A wide variety of tumorigenic mechanisms involved in chronic Cd exposure and the beneficial effects of flavonoids against Cd-induced carcinogenicity necessitate further investigations.</p

Phase Ib/Ii Study of Lacnotuzumab in Combination With Spartalizumab in Patients With advanced Malignancies

INTRODUCTION: Blocking the colony-stimulating factor 1 (CSF-1) signal on tumor-associated macrophages can lead to an upregulation of checkpoint molecules, such as programmed cell death ligand 1 (PD-L1), thus causing resistance to this blockade. Combining spartalizumab (PDR001), a high-affinity, ligand-blocking, humanized anti-PD-1 immunoglobulin G4 antibody, with lacnotuzumab (MCS110), a high-affinity, humanized monoclonal antibody directed against human CSF-1 can potentially overcome this resistance. METHODS: This was a multicenter, phase Ib/II trial using a combination of spartalizumab with lacnotuzumab in patients with advanced cancers, including anti-PD-1/PD-L1 treatment-resistant melanoma, and anti-PD-1/PD-L1 treatment-naïve triple-negative breast cancer, pancreatic cancer, and endometrial cancer (ClinicalTrials.gov identifier: NCT02807844). The primary objective of dose escalation phase Ib was to assess safety, tolerability, and recommended phase II dose. The primary objective of the phase II expansion study was to assess the combination\u27s antitumor activity, including objective response rate and clinical benefit rate. RESULTS: A total of eight patients (five in phase Ib and three in phase II) were evaluable for adverse events (AEs) at our study site. All eight patients experienced at least grade 1 AE. The most common treatment-related AEs were increased serum aspartate aminotransferase (38%), fatigue (38%), anemia (25%), increased alkaline phosphatase (25%), hyperbilirubinemia (25%), hypocalcemia (25%), and hypoalbuminemia (25%). Most of these AEs were grade 1 or 2. None of the patients experienced grade 4 AEs and no drug-related fatal AEs were reported among the eight patients treated in the study. One (13%) patient had stable disease (SD) (captured as unknown by the study sponsor because the evaluation criteria set per protocol was not met) and three (38%) patients had progressive disease. Four (50%) patients developed clinical disease progression based on investigator evaluation. One patient with pancreatic cancer achieved immune-related SD for 26 months while on the study treatments. CONCLUSION: The study completed phase Ib dose escalation and phase II. However, gating criteria for efficacy were not met for expansion beyond 80 patients in phase II and the sponsor did not continue development of the combination of spartalizumab and lacnotuzumab for oncology indications. The potential signal of activity in pancreatic cancer should be further explored

Epigenetic-Mediated Antimicrobial Resistance:Host versus Pathogen Epigenetic Alterations

Since the discovery of antibiotics, humans have been benefiting from them by decreasing the morbidity and mortality associated with bacterial infections. However, in the past few decades, misuse of antibiotics has led to the emergence of bacterial infections resistant to multiple drugs, a significant health concern. Bacteria exposed to inappropriate levels of antibiotics lead to several genetic changes, enabling them to survive in the host and become more resistant. Despite the understanding and targeting of genetic-based biochemical changes in the bacteria, the increasing levels of antibiotic resistance are not under control. Many reports hint at the role of epigenetic modifications in the bacterial genome and host epigenetic reprogramming due to interaction with resistant pathogens. Epigenetic changes, such as the DNA-methylation-based regulation of bacterial mutation rates or bacteria-induced histone modification in human epithelial cells, facilitate its long-term survival. In this review article, epigenetic changes leading to the development of antibiotic resistance in clinically relevant bacteria are discussed. Additionally, recent lines of evidence focusing on human host epigenetic changes due to the human–pathogen interactions are presented. As genetic mechanisms cannot explain the transient nature of antimicrobial resistance, we believe that epigenetics may provide new frontiers in antimicrobial discovery.</p

Epigenetic Mediated Antimicrobial Resistance:Host versus Pathogen Epigenetic Alterations

Since the discovery of antibiotics, humans have been benefiting from them by decreasing the morbidity and mortality associated with bacterial infections. However, in the past few decades, misuse of antibiotics has led to the emergence of bacterial infections resistant to multiple drugs, a significant health concern. Bacteria exposed to inappropriate levels of antibiotics lead to several genetic changes, enabling them to survive in the host and become more resistant. Despite the understanding and targeting of genetic-based biochemical changes in the bacteria, the increasing levels of antibiotic resistance are not under control. Many reports hint at the role of epigenetic modifications in the bacterial genome and host epigenetic reprogramming due to interaction with resistant pathogens. Epigenetic changes, such as the DNA-methylation-based regulation of bacterial mutation rates or bacteria-induced histone modification in human epithelial cells, facilitate its long-term survival. In this review article, epigenetic changes leading to the development of antibiotic resistance in clinically relevant bacteria are discussed. Additionally, recent lines of evidence focusing on human host epigenetic changes due to the human–pathogen interactions are presented. As genetic mechanisms cannot explain the transient nature of antimicrobial resistance, we believe that epigenetics may provide new frontiers in antimicrobial discovery

Evaluation of the gulf of aqaba coastal water, Jordan

© 2020 by the authors. (1) Background: The Gulf of Aqaba (GoA) supports unique and diverse marine ecosystems. It is one of the highest anthropogenically impacted coasts in the Middle East region, where rapid human activities are likely to degrade these naturally diverse but stressed ecosystems. (2) Methods: Various water quality parameters were measured to assess the current status and conditions of GoA seawater including pH, total dissolved solids (TDS), total alkalinity (TA), Cl-, NO3-, SO42-, PO43-, NH4+, Ca2+, Mg2+, Na+, K+, Sr, Cd, Co, Cr, Cu, Fe, Mn, Pb, and Zn. (3) Results: The pH values indicated basic coastal waters. The elevated levels of TDS with an average of about 42 g/L indicated highly saline conditions. Relatively low levels of inorganic nutrients were observed consistent with the prevalence of oligotrophic conditions in GoA seawater. The concentrations of Ca2+, Mg2+, Na+, K+, Sr, Cl-, and SO42- in surface layer varied spatially from about 423-487, 2246-2356, 9542-12,647, 513-713, 9.2-10.4, 22,173-25,992, and 317-407 mg/L, respectively. The average levels of Cd, Co, Cr, Cu, Fe, Mn, Pb and Zn ranged from 0.51, 0.38, 1.44, 1.29, 0.88, 0.38, and 6.05 μg/L, respectively. (4) Conclusions: The prevailing saline conditions of high temperatures, high evaporation rates, the water stratification and intense dust storms are major contributing factors to the observed seawater chemistry. The surface distribution of water quality variables showed spatial variations with no specific patterns, except for metal contents which exhibited southward increasing trends, closed to the industrial complex. The vast majority of these quality parameters showed relatively higher values compared to those of other regions