28 research outputs found
Problems experienced by secondary school deputy principals in diverse contexts: a South African study
This paper reports on research that was undertaken to determine the problems experienced by deputy principals in secondary schools, and the extent to which these problems were experienced. Although some research was conducted on the deputy principalship, no research treats the problems that deputy principals experience upon appointment comprehensively. An understanding of the problems experienced by secondary school deputy principals is a necessary precursor of an induction program to address the problems. A quantitative approach which was underpinned by the post-positivist paradigm was adopted. In order to determine the extent to which the problems were experienced, a survey was conducted among one hundred and fifty seven secondary school deputy principals in the North West Province. The participants came from a diverse context of rural, township and urban schools. The deputy principals who participated in the study included those who were newly appointed (one to three years of service) and those who were experienced (more than three years of service). Data were analyzed by means of descriptive statistics such as frequencies, means and percentages. There were no significant differences in the responses of both newly-appointed and experienced deputy principals. The results revealed that deputy principals experienced administrative, financial management, work pressure, personal and physical resources problems. In an attempt to address the problems identified, a context-specific induction program is recommended. The induction program should be an on-going program of professional development and should preferably include specific aims, action steps to be taken to achieve the aims that are set and measures to evaluate progress
METHODOLOGY Open Access
The development and validation of an LC-MS/MS method for the determination of a new anti-malarial compound (TK900D) in human whole blood and its application to pharmacokinetic studies in mic
The development and validation of an LC-MS/MS method for the determination of a new anti-malarial compound (TK900D) in human whole blood and its application to pharmacokinetic studies in mice
Abstract
Background
Malaria is one of the most lethal and life-threatening killer infectious diseases in the world, and account for the deaths of more than half a million people annually. Despite the remarkable achievement made in preventing and eradicating malaria, it still remains a threat to the public health and a burden to the global economy due to the emergence of multiple-drug resistant malaria parasites. Therefore, the need to develop new anti-malarial drugs is crucial. The chemistry department at the University of Cape Town synthesized a number of new CQ-like derivatives (TK-series), and evaluated them for in vitro activity against both CQ-sensitive and -resistant Plasmodium falciparum strains, and for general cytotoxicity against a Chinese Hamster Ovarian (CHO) mammalian cell line. The lead compounds from the TK-series were selected for a comprehensive pharmacokinetic (PK) evaluation in a mouse model.
Methods
A sensitive LC-MS/MS assay was developed for the quantitative determination of TK900D. Multiple reaction monitoring (MRM) in the positive ionization mode was used for detection. The analyte and the internal standard (TK900E) were isolated from blood samples by liquid-liquid extraction with ethyl acetate. Chromatographic separation was achieved with a Phenomenex® Kinetex C18 (100 × 2.0 mm id, 2.6 μm) analytical column, using a mixture of 0.1% formic acid and acetonitrile (50:50; v/v) as the mobile phase. The method was fully validated over concentrations that ranged from 3.910 to 1000 ng/ml, and used to evaluate the PK properties of the lead compounds in a mouse model.
Results
The assay was robust, with deviation not exceeding 11% for the intra- and inter-run precision and accuracy. Extraction recovery was consistent and more than 60%. PK evaluation showed that TK900D and TK900E have moderate oral bioavailability of 30.8% and 25.9%, respectively. The apparent half-life ranged between 4 to 6Â h for TK900D and 3.6 to 4Â h for TK900E.
Conclusion
The assay was sensitive and able to measure accurately low drug levels from a small sample volume (20 μl). PK evaluation showed that the oral bioavailability was moderate. Therefore, from a PK perspective, the compounds look promising and can be taken further in the drug development process
Recreational fish-finders - an inexpensive alternative to scientific echo-sounders for unravelling the links between marine top predators and their prey
Studies investigating how mobile marine predators respond to their prey are limited due to the challenging nature of the environment. While marine top predators are increasingly easy to study thanks to developments in bio-logging technology, typically there is scant information on the distribution and abundance of their prey, largely due to the specialised nature of acquiring this information. We explore the potential of using single-beam recreational fish-finders (RFF) to quantify relative forage fish abundance and draw inferences of the prey distribution at a fine spatial scale. We compared fish school characteristics as inferred from the RFF with that of a calibrated scientific split-beam echo-sounder (SES) by simultaneously operating both systems from the same vessel in Algoa Bay, South Africa. Customized open-source software was developed to extract fish school information from the echo returns of the RFF. For schools insonified by both systems, there was close correspondence between estimates of mean school depth (R 2 = 0.98) and school area (R 2 = 0.70). Estimates of relative school density (mean volume backscattering strength; S v ) measured by the RFF were negatively biased through saturation of this system given its smaller dynamic range. A correction factor applied to the RFF-derived density estimates improved the comparability between the two systems. Relative abundance estimates using all schools from both systems were congruent at scales from 0.5 km to 18 km with a strong positive linear trend in model fit estimates with increasing scale. Although absolute estimates of fish abundance cannot be derived from these systems, they are effective at describing prey school characteristics and have good potential for mapping forage fish distribution and relative abundance. Using such relatively inexpensive systems could greatly enhance our understanding of predator-prey interactions
A urinary biosignature for mitochondrial myopathy, encephalopathy, lactic acidosis and stroke like episodes (MELAS)
We used a comprehensive metabolomics approach to study the altered urinary metabolome of two mitochondrial myopathy, encephalopathy lactic acidosis and stroke like episodes (MELAS) cohorts carrying the m.3243A > G mutation. The first cohort were used in an exploratory phase, identifying 36 metabolites that were significantly perturbed by the disease. During the second phase, the 36 selected metabolites were able to separate a validation cohort of MELAS patients completely from their respective control group, suggesting usefulness of these 36 markers as a diagnostic set. Many of the 36 perturbed metabolites could be linked to an altered redox state, fatty acid catabolism and one-carbon metabolism. However, our evidence indicates that, of all the metabolic perturbations caused by MELAS, stalled fatty acid oxidation prevailed as being particularly disturbed. The strength of our study was the utilization of five different analytical platforms to generate the robust metabolomics data reported here. We show that urine may be a useful source for disease-specific metabolomics data, linking, amongst others, altered one-carbon metabolism to MELAS. The results reported here are important in our understanding of MELAS and might lead to better treatment options for the disease.Peer reviewe
Tannin Fingerprinting in Vegetable Tanned Leather by Solid State NMR Spectroscopy and Comparison with Leathers Tanned by Other Processes
Solid state 13C-NMR spectra of pure tannin powders from four different sources – mimosa, quebracho, chestnut and tara – are readily distinguishable from each other, both in pure commercial powder form, and in leather which they have been used to tan. Groups of signals indicative of the source, and type (condensed vs. hydrolyzable) of tannin used in the manufacture are well resolved in the spectra of the finished leathers. These fingerprints are compared with those arising from leathers tanned with other common tanning agents. Paramagnetic chromium (III) tanning causes widespread but selective disappearance of signals from the spectrum of leather collagen, including resonances from acidic aspartyl and glutamyl residues, likely bound to Cr (III) structures. Aluminium (III) and glutaraldehyde tanning both cause considerable leather collagen signal sharpening suggesting some increase in molecular structural ordering. The 27Al-NMR signal from the former material is consistent with an octahedral coordination by oxygen ligands. Solid state NMR thus provides easily recognisable reagent specific spectral fingerprints of the products of vegetable and some other common tanning processes. Because spectra are related to molecular properties, NMR is potentially a powerful tool in leather process enhancement and quality or provenance assurance
Syntheses and in Vitro Antiplasmodial Activity of Aminoalkylated Chalcones and Analogues
A series of readily synthesized and
inexpensive aminoalkylated
chalcones and diarylpropane analogues (<b>1</b>–<b>55</b>) were synthesized and tested against chloroquinone-sensitive
(D10 and NF54) and -resistant (Dd2 and K1) strains of <i>Plasmodium
falciparum</i>. Hydrogenation of the enone to a diarylpropane
moiety increased antiplasmodial bioactivity significantly. The influence
of the structure of the amine moiety, A-ring substituents, propyl
vs ethyl linker, and chloride salt formation on further enhancing
antiplasmodial activity was investigated. Several compounds have IC<sub>50</sub> values similar to or better than chloroquine (CQ). The most
active compound (<b>26</b>) had an IC<sub>50</sub> value of
0.01 μM. No signs of resistance were detected, as can be expected
from compounds with structures unrelated to CQ and other currently
used antimalarial drugs. Toxicity tests (in vitro CHO cell assay)
gave high SI indices
Flow diagram illustrating the workflow of FISH software showing the different steps in the processing phase (steps 1–3) and the review phase (step 4).
<p>Flow diagram illustrating the workflow of FISH software showing the different steps in the processing phase (steps 1–3) and the review phase (step 4).</p
Plots for three scenarios, 1–3, representing three schools selected from the recreational fish-finder (RFF) outputs with different pixel skewness values: a) 2D scatter plots showing the influence of different combinations of mean volume backscattering strength (Sv) starting values and colour step values on the difference in Sv values (Sv diff) between the RFF and the scientific echosounder (SES) outputs (colour scale bar—low values indicate optimal estimates), cross-hatch denotes optimal colour step values at starting values of -65 dB; b) least-squares regressions between volume backscattering coefficients (sv¯) of the SES (transformed) and RFF outputs of the 36 matched schools using starting and colour step values for the RFF outputs as determined by the 2D scatter plot analyses, coefficients are given at the top of each plot and shaded areas denote the 95% confidence intervals; c) histograms showing the frequency of schools in 4 dB S<sub>v</sub> bins for the SES-derived schools, the
<p>Plots for three scenarios, 1–3, representing three schools selected from the recreational fish-finder (RFF) outputs with different pixel skewness values: a) 2D scatter plots showing the influence of different combinations of mean volume backscattering strength (Sv) starting values and colour step values on the difference in Sv values (Sv diff) between the RFF and the scientific echosounder (SES) outputs (colour scale bar—low values indicate optimal estimates), cross-hatch denotes optimal colour step values at starting values of -65 dB; b) least-squares regressions between volume backscattering coefficients (<math><mrow><msub><mrow><mi>s</mi></mrow><mrow><mi>v</mi></mrow></msub></mrow><mo>¯</mo></math>) of the SES (transformed) and RFF outputs of the 36 matched schools using starting and colour step values for the RFF outputs as determined by the 2D scatter plot analyses, coefficients are given at the top of each plot and shaded areas denote the 95% confidence intervals; c) histograms showing the frequency of schools in 4 dB S<sub>v</sub> bins for the SES-derived schools, the RFF-derived schools before application of a correction factor as predicted by the linear regression models (b), and the RFF-derived schools with this correction factor applied (RFF corr).</p