Overcoming beta-agonist tolerance: high dose salbutamol and ipratropium bromide. Two randomised controlled trials

BACKGROUND: Asthmatics treated with long-acting beta-agonists have a reduced bronchodilator response to moderate doses of inhaled short acting beta-agonists during acute bronchoconstriction. It is not known if the response to higher doses of nebulised beta-agonists or other bronchodilators is impaired. We assessed the effect of long-acting beta-agonist treatment on the response to 5 mg nebulised salbutamol and to ipratropium bromide. METHODS: Two double-blind, placebo-controlled, crossover studies of inhaled formoterol 12 μg twice daily in patients with asthma. High-dose salbutamol: 36 hours after the last dose of 1 week of formoterol or placebo treatment, 11 subjects inhaled methacholine to produce a 20% fall in FEV(1). Salbutamol 5 mg was then administered via nebuliser and the FEV(1 )was monitored for 20 minutes. Ipratropium: 36 hours after the last dose of 1 week of formoterol or placebo treatment, 11 subjects inhaled 4.5% saline to produce a 20% fall in FEV(1). Salbutamol 200 μg or ipratropium bromide 40 μg was then inhaled and the FEV(1 )was monitored for 30 minutes. Four study arms compared the response to each bronchodilator after formoterol and placebo. Analyses compared the area under the bronchodilator response curves, adjusting for changes in pre-challenge FEV(1), dose of provocational agent and FEV(1 )fall during the challenge procedure. RESULTS: The response to nebulised salbutamol was 15% lower after formoterol therapy compared to placebo (95% confidence 5 to 25%, p = 0.008). The response to ipratropium was unchanged. CONCLUSION: Long-acting beta-agonist treatment induces tolerance to the bronchodilator effect of beta-agonists, which is not overcome by higher dose nebulised salbutamol. However, the bronchodilator response to ipratropium bromide is unaffected

The role of fossils in interpreting the development of the Karoo Basin

Main articleThe Permo-Carboniferous to Jurassic aged rocks off the main Karoo Basin of South Africa are world renowned for the wealth of synapsid reptile and early dinosaur fossils, which have allowed a ten-fold biostratigraphic subdivision of the Karoo Supergroup to be erected. The role of fossils in interpreting the development of the Karoo Basin is not, however, restricted to biostratigraphic studies. Recent integrated sedimentological and palaeontological studies have helped in more precisely defining a number of problematical formational contacts within the Karoo Supergroup, as well as enhancing palaeoenvironmental reconstructions, and basin development models.Non

A taxonomic note concerning a dicynodont (Synapsida: Anomodontia) from the Middle Triassic of East Africa

Main articleThe complicated histories of the Indian dicynodont Rechnisaurus and the East African dicynodont Kannemeyeria cristarhynchus has led to the incorrect use of the name ‘cristarhynchus’ for the latter taxon. This paper therefore proposes a new species name and diagnosis.The National Research Foundation and University Research Committee of the University of the Witwatersran

Biostratigraphy of the lower Burgersdorp Formation (Beaufort Group; Karoo Supergroup) of South Africa – implications for the stratigraphic ranges of early Triassic tetrapods

The Beaufort Group (Karoo Supergroup) of South Africa comprises a thick sequence of fluvio-lacustrine sedimentary rocks that accumulated in a landlocked, intracratonic foreland basin in southwestern Gondwana during the Middle Permian to Middle Triassic. To the south this basin was bounded by the Cape Fold Belt, which acted as the major source of both sediment and discharge. Rocks of the Beaufort Group are renowned for their rich fossil record and eight tetrapod-based biozones are currently recognized. The uppermost two biozones of the Beaufort Group, the Lystrosaurus and Cynognathus assemblage zones, record terrestrial biotic recovery following the Permo-Triassic mass extinction event. Stratigraphic overlap between these biozones occurs in the proximal sector, but their separation by an unconformity in the distal sector reflects the incomplete preservation of the sequence in this part of the basin. Our results afford chronostratographic control that impacts on current theories on the development of the Karoo Basin, and on the relative age of the sequence.South African Council for Geoscience, the University of the Witwatersrand and the National Research Foundation

Comparison of dimethyl sulfoxide treated highly conductive poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) electrodes for use in indium tin oxide-free organic electronic photovoltaic devices

Indium tin oxide (ITO)-free organic photovoltaic (OPV) devices were fabricated using highly conductive poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) as the transparent conductive electrode (TCE). The intrinsic conductivity of the PEDOT:PSS films was improved by two different dimethyl sulfoxide (DMSO) treatments – (i) DMSO was added directly to the PEDOT:PSS solution (PEDOT:PSSADD) and (ii) a pre-formed PEDOT:PSS film was immersed in DMSO (PEDOT:PSSIMM). X-ray photoelectron spectroscopy (XPS) and conductive atomic force microscopy (CAFM) studies showed a large amount of PSS was removed from the PEDOT:PSSIMM electrode surface. OPV devices based on a poly(3-hexylthiophene):[6,6]-phenyl-C61-butyric acid methyl ester (P3HT:PCBM) bulk hetrojunction showed that the PEDOT:PSSIMM electrode out-performed the PEDOT:PSSADD electrode, primarily due to an increase in short circuit current density from 6.62 mA cm−2 to 7.15 mA cm−2. The results highlight the importance of optimising the treatment of PEDOT:PSS electrodes and demonstrate their potential as an alternative TCE for rapid processing and low-cost OPV and other organic electronic devices

A diverse diapsid tooth assemblage from the Early Triassic (Driefontein locality, South Africa) records the recovery of diapsids following the end-Permian mass extinction

Mass extinctions change the trajectory of evolution and restructure ecosystems. The largest mass extinction, the end-Permian, is a particularly interesting case due to the hypothesized delay in the recovery of global ecosystems, where total trophic level recovery is not thought to have occurred until 5–9 million years after the extinction event. Diapsids, especially archosauromorphs, play an important role in this recovery, filling niches left vacant by therapsids and anapsids. However, the nature of lineage and ecological diversification of diapsids is obscured by the limited number of continuous, well-dated stratigraphic sections at the Permian-Triassic boundary and continuing through the first half of the Triassic. The Karoo Basin of South Africa is one such record, and particularly the late Early Triassic (Olenekian) Driefontein locality fills this gap in the diapsid fossil record. We collected a total of 102 teeth of which 81 are identified as diapsids and the remaining 21 as identified as temnospondyls. From the sample, seven distinct tooth morphotypes of diapsids are recognized, six of which are new to the locality. We used a combination of linear measurements, 3D geomorphometrics, and nMDS ordination to compare these morphotypes and made inferences about their possible diets. Although the morphotypes are readily differentiated in nMDS, the overall morphological disparity is low, and we infer five morphotypes are faunivorous with the other two potentially omnivorous or piscivorous based on their morphological similarities with dentitions from extant diapsids, demonstrating an unsampled taxonomic and ecological diversity of diapsids in the Early Triassic based on teeth. Although ecological specialization at Driefontein may be low, it records a diversity of diapsid taxa, specifically of archosauromorph lineages

A new algorithm to diagnose atrial ectopic origin from multi lead ECG systems - insights from 3D virtual human atria and torso

Rapid atrial arrhythmias such as atrial fibrillation (AF) predispose to ventricular arrhythmias, sudden cardiac death and stroke. Identifying the origin of atrial ectopic activity from the electrocardiogram (ECG) can help to diagnose the early onset of AF in a cost-effective manner. The complex and rapid atrial electrical activity during AF makes it difficult to obtain detailed information on atrial activation using the standard 12-lead ECG alone. Compared to conventional 12-lead ECG, more detailed ECG lead configurations may provide further information about spatio-temporal dynamics of the body surface potential (BSP) during atrial excitation. We apply a recently developed 3D human atrial model to simulate electrical activity during normal sinus rhythm and ectopic pacing. The atrial model is placed into a newly developed torso model which considers the presence of the lungs, liver and spinal cord. A boundary element method is used to compute the BSP resulting from atrial excitation. Elements of the torso mesh corresponding to the locations of the placement of the electrodes in the standard 12-lead and a more detailed 64-lead ECG configuration were selected. The ectopic focal activity was simulated at various origins across all the different regions of the atria. Simulated BSP maps during normal atrial excitation (i.e. sinoatrial node excitation) were compared to those observed experimentally (obtained from the 64-lead ECG system), showing a strong agreement between the evolution in time of the simulated and experimental data in the P-wave morphology of the ECG and dipole evolution. An algorithm to obtain the location of the stimulus from a 64-lead ECG system was developed. The algorithm presented had a success rate of 93%, meaning that it correctly identified the origin of atrial focus in 75/80 simulations, and involved a general approach relevant to any multi-lead ECG system. This represents a significant improvement over previously developed algorithms

An Acheulean handaxe from Gladysvale Cave site, Gauteng, South Africa.

WE DESCRIBE A SINGLE HANDAXE FROM fossiliferous breccias at Gladysvale Cave, South Africa. The artefact is the only known tool so far discovered during the controlled excavations conducted at this site over the last decade, and was recovered from decalcified sediments near the stratigraphic interface of two breccia units, making it difficult to assign it with confidence to either. The morphology of the handaxe indicates a middle-late Acheulean industry, and preliminary electron spin resonance and palaeomagnetic dating suggest an age of greater than 780 000 years.NCS2016http://hdl.handle.net/10520/EJC9652

Vitamin D, innate immunity and outcomes in community acquired pneumonia

We investigated the associations between vitamin D status, the antimicrobial peptides cathelicidin and beta defensin-2 and outcomes in community acquired pneumonia. In hospitalised patients with community acquired pneumonia, vitamin D deficiency but not antimicrobial peptide levels were associated with increased 30-day mortality. Vitamin D was not associated with levels of the antimicrobial peptide cathelicidin or beta defensin-2