Geospatial modelling of watershed peak flood discharge in Selangor, Malaysia

© 2019 by the authors. Conservative peak flood discharge estimation methods such as the rational method do not take into account the soil infiltration of the precipitation, thus leading to inaccurate estimations of peak discharges during storm events. The accuracy of estimated peak flood discharge is crucial in designing a drainage system that has the capacity to channel runoffs during a storm event, especially cloudbursts and in the analysis of flood prevention and mitigation. The aim of this study was to model the peak flood discharges of each sub-watershed in Selangor using a geographic information system (GIS). The geospatial modelling integrated the watershed terrain model, the developed Soil Conservation Service Curve Cumber (SCS-CN) and precipitation to develop an equation for estimation of peak flood discharge. Hydrological Engineering Center-Hydrological Modeling System (HEC-HMS) was used again to simulate the rainfall-runoffbased on the Clark-unit hydrograph to validate the modelled estimation of peak flood discharge. The estimated peak flood discharge showed a coefficient of determination, r2 of 0.9445, when compared with the runoffsimulation of the Clark-unit hydrograph. Both the results of the geospatial modelling and the developed equation suggest that the peak flood discharge of a sub-watershed during a storm event has a positive relationship with the watershed area, precipitation and Curve Number (CN), which takes into account the soil bulk density and land-use of the studied area, Selangor in Malaysia. The findings of the study present a comparable and holistic approach to the estimation of peak flood discharge in a watershed which can be in the absence of a hydrodynamic simulation model

Diagnostics and the challenge of antimicrobial resistance: a survey of UK livestock veterinarians’ perceptions and practices

This is the author accepted manuscript. The final version is available from BMJ Publishing Group via the DOI in this recordBackground This paper explores the current role and place of diagnostic tests in the treatment of farm animal disease. With the growing focus on reduced reliance on antibiotic medicines in both animal and human patient care, attention is increasingly being focused on the practice, the technology and the function of diagnostic tests and how these can support responsible antimicrobial use. Emerging diagnostic technologies offer the possibility of more rapid testing for bacterial disease, while food chain actors and others are increasingly seeking to make diagnostic tests mandatory before the use of critically important antibiotics. Method This paper reports the findings of a recent large-scale online survey of UK farm animal veterinarians (n=153) which investigated current veterinary diagnostic practice with particular attention to the relationship between diagnostic test use and antibiotic treatment. Results Results revealed a range of factors that influence veterinary diagnostic practice and demonstrate the continuing importance of clinical observation and animal/herd knowledge in the selection of antibiotic treatment. Conclusion The findings identify a considerable ambivalence on the part of farm animal veterinarians regarding the current and future uses of rapid and point-of-care diagnostic tests as a means of improving clinical diagnosis and addressing inappropriate antibiotic medicine use.Economic and Social Research Council (ESRC

In vitro Anti-proliferative and Apoptotic Activities of Eurycoma longifolia Jack (Simaroubaceae) on HL-60 Cell Line

Purpose: To investigate the anti-proliferative, apoptotic and differentiating activities of Eurycoma longifolia root extracts on HL-60 leukemic cells.Methods: HL-60 cells were treated with different partially purified sub-fractions (F1 – F3) derived from the resin chromatography of the crude methanol root extract of E. longifolia roots, at different doses andtime points. The anti-proliferative activity of E. longifolia was assessed via cell counting and trypan blue exclusion. Apoptosis was evaluated via Annexin-V FITC/IP and Hoechst staining. Flow cytometry and Wright staining were used to assess its differentiation activities.Results: F1 showed unremarkable growth inhibition rate while F2 and F3 showed growth inhibitory effects with median inhibitory concentration (IC50) values of 15.2 and 28.6 ìg/ml, respectively. Treatment with F2 and F3 (100 ìg/ml) for 96 h increased cell death from 3.3 to 95.5 and 76.3 %,respectively. Treatment with F2 (50 ìg/ml) induced apoptosis by 14, 19.5 and 25 % after 24, 48 and 72 h, respectively. No differentiation activity was observed, as indicated by absence of myeloid maturation and a non-significant CD14 positivity (p > 0.05).Conclusion: E. longifolia extract (F2) showed promising anti-leukemic activity and can be a candidate for the development of a drug for the treatment of acute promyelocytic leukemia (APL).Keywords: Acute promyelocytic leukemia (APL), HL-60 cells, Eurycoma longifolia, Apoptosis, Antiproliferation, Differentiatio

Lipid profiles and outcomes of patients with prior cancer and subsequent myocardial infarction or stroke

Patients with cancer are at increased risk of myocardial infarction (MI) and stroke. Guidelines do not address lipid profile targets for these patients. Within the lipid profiles, we hypothesized that patients with cancer develop MI or stroke at lower low density lipoprotein cholesterol (LDL-C) concentrations than patients without cancer and suffer worse outcomes. We linked nationwide longitudinal MI, stroke and cancer registries from years 2007-2017. We identified 42,148 eligible patients with MI (2421 prior cancer; 39,727 no cancer) and 43,888 eligible patients with stroke (3152 prior cancer; 40,738 no cancer). Median LDL-C concentration was lower in the prior cancer group than the no cancer group at incident MI [2.43 versus 3.10 mmol/L, adjusted ratio 0.87 (95% CI 0.85-0.89)] and stroke [2.81 versus 3.22 mmol/L, adjusted ratio 0.93, 95% CI 0.91-0.95)]. Similarly, median triglyceride and total cholesterol concentrations were lower in the prior cancer group, with no difference in high density lipoprotein cholesterol. Prior cancer was associated with higher post-MI mortality [adjusted hazard ratio (HR) 1.48, 95% CI 1.37-1.59] and post-stroke mortality (adjusted HR 1.95, 95% CI 1.52-2.52). Despite lower LDL-C concentrations, patients with prior cancer had worse post-MI and stroke mortality than patients without cancer

Alginate inhibits iron absorption from ferrous gluconate in a randomized controlled trial and reduces iron uptake into Caco-2 cells

Previous in vitro results indicated that alginate beads might be a useful vehicle for food iron fortification. A human study was undertaken to test the hypothesis that alginate enhances iron absorption. A randomised, single blinded, cross-over trial was carried out in which iron absorption was measured from serum iron appearance after a test meal. Overnight-fasted volunteers (n=15) were given a test meal of 200g cola-flavoured jelly plus 21 mg iron as ferrous gluconate, either in alginate beads mixed into the jelly or in a capsule. Iron absorption was lower from the alginate beads than from ferrous gluconate (8.5% and 12.6% respectively, p=0.003). Sub-group B (n=9) consumed the test meals together with 600 mg calcium to determine whether alginate modified the inhibitory effect of calcium. Calcium reduced iron absorption from ferrous gluconate by 51%, from 11.5% to 5.6% (p=0.014), and from alginate beads by 37%, from 8.3% to 5.2% (p=0.009). In vitro studies using Caco-2 cells were designed to explore the reasons for the difference between the previous in vitro findings and the human study; confirmed the inhibitory effect of alginate. Beads similar to those used in the human study were subjected to simulated gastrointestinal digestion, with and without cola jelly, and the digestate applied to Caco-2 cells. Both alginate and cola jelly significantly reduced iron uptake into the cells, by 34% (p=0.009) and 35% (p=0.003) respectively. The combination of cola jelly and calcium produced a very low ferritin response, 16.5% (p<0.001) of that observed with ferrous gluconate alone. The results of these studies demonstrate that alginate beads are not a useful delivery system for soluble salts of iron for the purpose of food fortification

A Compensatory Mutation Provides Resistance to Disparate HIV Fusion Inhibitor Peptides and Enhances Membrane Fusion

Fusion inhibitors are a class of antiretroviral drugs used to prevent entry of HIV into host cells. Many of the fusion inhibitors being developed, including the drug enfuvirtide, are peptides designed to competitively inhibit the viral fusion protein gp41. With the emergence of drug resistance, there is an increased need for effective and unique alternatives within this class of antivirals. One such alternative is a class of cyclic, cationic, antimicrobial peptides known as θ-defensins, which are produced by many non-human primates and exhibit broad-spectrum antiviral and antibacterial activity. Currently, the θ-defensin analog RC-101 is being developed as a microbicide due to its specific antiviral activity, lack of toxicity to cells and tissues, and safety in animals. Understanding potential RC-101 resistance, and how resistance to other fusion inhibitors affects RC-101 susceptibility, is critical for future development. In previous studies, we identified a mutant, R5-tropic virus that had evolved partial resistance to RC-101 during in vitro selection. Here, we report that a secondary mutation in gp41 was found to restore replicative fitness, membrane fusion, and the rate of viral entry, which were compromised by an initial mutation providing partial RC-101 resistance. Interestingly, we show that RC-101 is effective against two enfuvirtide-resistant mutants, demonstrating the clinical importance of RC-101 as a unique fusion inhibitor. These findings both expand our understanding of HIV drug-resistance to diverse peptide fusion inhibitors and emphasize the significance of compensatory gp41 mutations. © 2013 Wood et al

Viral Hepatitis and Rapid Diagnostic Test Based Screening for HBsAg in HIV-infected Patients in Rural Tanzania.

\ud \ud Co-infection with hepatitis B virus (HBV) is highly prevalent in people living with HIV in Sub-Saharan Africa. Screening for HBV surface antigen (HBsAg) before initiation of combination antiretroviral therapy (cART) is recommended. However, it is not part of diagnostic routines in HIV programs in many resource-limited countries although patients could benefit from optimized antiretroviral therapy covering both infections. Screening could be facilitated by rapid diagnostic tests for HBsAg. Operating experience with these point of care devices in HIV-positive patients in Sub-Saharan Africa is largely lacking. We determined the prevalence of HBV and Hepatitis C virus (HCV) infection as well as the diagnostic accuracy of the rapid test device Determine HBsAg in an HIV cohort in rural Tanzania. Prospectively collected blood samples from adult, HIV-1 positive and antiretroviral treatment-naïve patients in the Kilombero and Ulanga antiretroviral cohort (KIULARCO) in rural Tanzania were analyzed at the point of care with Determine HBsAg, a reference HBsAg EIA and an anti-HCV EIA. Samples of 272 patients were included. Median age was 38 years (interquartile range [IQR] 32-47), 169/272 (63%) subjects were females and median CD4+ count was 250 cells/µL (IQR 97-439). HBsAg was detected in 25/272 (9.2%, 95% confidence interval [CI] 6.2-13.0%) subjects. Of these, 7/25 (28%) were positive for HBeAg. Sensitivity of Determine HBsAg was rated at 96% (95% CI 82.8-99.6%) and specificity at 100% (95% CI, 98.9-100%). Antibodies to HCV (anti-HCV) were found in 10/272 (3.7%, 95% CI 2.0-6.4%) of patients. This study reports a high prevalence of HBV in HIV-positive patients in a rural Tanzanian setting. The rapid diagnostic test Determine HBsAg is an accurate assay for screening for HBsAg in HIV-1 infected patients at the point of care and may further help to guide cART in Sub-Saharan Africa