Antibiotic prescribing practice and adherence to guidelines in primary care in the Cape Town Metro District, South Africa

Background. Knowledge of antibiotic prescribing practice in primary care in South Africa is limited. As 80% of human antibiotic use is in primary care, this knowledge is important in view of the global problem of antibiotic resistance.Objectives. To assess antibiotic prescribing in primary care facilities in the Cape Town Metro District and compare it with current national guidelines, and to assess the reasons why prescriptions were not adherent to guidelines.Methods. A retrospective medical record review was performed in April/May 2016. Records of all patients seen over 2 days in each of eight representative primary care facilities in the Cape Town Metro District were reviewed. The treatment of any patient who raised a new complaint on either of those days was recorded. Prophylactic antibiotic courses, tuberculosis treatment and patients with a non-infection diagnosis were excluded. Treatment was compared with the Standard Treatment Guidelines and Essential Medicines List for South Africa, Primary Healthcare Level, 2014 edition.Results. Of 654 records included, 68.7% indicated that an antibiotic had been prescribed. Overall guideline adherence was 45.1%. Adherence differed significantly between facilities and according to the physiological system being treated, whether the prescription was for an adult or paediatric patient, and the antibiotic prescribed. Healthcare professional type and patient gender had no significant effect on adherence. The main reasons for non-adherence were an undocumented diagnosis (30.5%), antibiotic not required (21.6%), incorrect dose (12.9%), incorrect drug (11.5%), and incorrect duration of therapy (9.5%).Conclusions. This study demonstrates poor adherence to guidelines. Irrational use of antibiotics is associated with increased antibiotic resistance. There is an urgent need to improve antibiotic prescribing practice in primary care in the Cape Town Metro District.

β-Glucan is a major growth substrate for human gut bacteria related to Coprococcus eutactus

A clone encoding carboxymethyl cellulase activity was isolated during functional screening of a human gut metagenomic library using Lactococcus lactis MG1363 as heterologous host. The insert carried a glycoside hydrolase family 9 (GH9) catalytic domain with sequence similarity to a gene from Coprococcus eutactus ART55/1. Genome surveys indicated a limited distribution of GH9 domains among dominant human colonic anaerobes. Genomes of C. eutactus-related strains harboured two GH9-encoding and four GH5-encoding genes, but the strains did not appear to degrade cellulose. Instead, they grew well on β-glucans and one of the strains also grew on galactomannan, galactan, glucomannan and starch. Coprococcus comes and Coprococcus catus strains did not harbour GH9 genes and were not able to grow on β-glucans. Gene expression and proteomic analysis of C. eutactus ART55/1 grown on cellobiose, β-glucan and lichenan revealed similar changes in expression in comparison to glucose. On β-glucan and lichenan only, one of the four GH5 genes was strongly upregulated. Growth on glucomannan led to a transcriptional response of many genes, in particular a strong upregulation of glycoside hydrolases involved in mannan degradation. Thus, β-glucans are a major growth substrate for species related to C. eutactus, with glucomannan and galactans alternative substrates for some strains

Exogenously added GPI-anchored tissue inhibitor of matrix metal loproteinase-1 (TIMP-1) displays enhanced and novel biological activities

The family of tissue inhibitors of metalloproteinases (TIMPs) exhibits diverse physiological/biological functions including the inhibition of active matrix metalloproteinases, regulation of proMMP activation, cell growth, and the modulation of angiogenesis. TIMP-1 is a secreted protein that can be detected on the cell surface through its interaction with surface proteins. The diverse biological functions of TIMP-1 are thought to lie, in part, in the kinetics of TIMP-1/MMP/surface protein interactions. Proteins anchored by glycoinositol phospholipids (GPIs), when purified and added to cells in vitro, are incorporated into their surface membranes. A GPI anchor was fused to TIMP-1 to generate a reagent that could be added directly to cell membranes and thus focus defined concentrations of TIMP-1 protein on any cell surface independent of protein-protein interaction. Unlike native TIMP-1, exogenously added GPI-anchored TIMP-1 protein effectively blocked release of MMP-2 and MMP-9 from osteosarcoma cells. TIMP-1-GP1 was a more effective modulator of migration and proliferation than TIMP-1. While control hTIMP-1 protein did not significantly affect migration of primary microvascular endothelial cells at the concentrations tested, the GPI-anchored TIMP-1 protein showed a pronounced suppression of endothelial cell migration in response to bFGF. In addition, TIMP-1-GPI was more effective at inducing microvascular endothelial proliferation. In contrast, fibroblast proliferation was suppressed by the agent. Reagents based on this method should assist in the dissection of the protease cascades and activities involved in TIMP biology. Membrane-fixed TIMP-1 may represent a more effective version of the protein for use in therapeutic expression

Chemical Evolution of Galaxies

Chemical evolution of galaxies brings together ideas on stellar evolution and nucleosynthesis with theories of galaxy formation, star formation and galaxy evolution, with all their associated uncertainties. In a new perspective brought about by the Hubble Deep Field and follow-up investigations of global star formation rates, diffuse background etc., it has become necessary to consider the chemical composition of dark baryonic matter as well as that of visible matter in galaxies.Comment: 6 pages, AAS LaTeX macros v5.0, Millennium Essay to appear in PASP, Feb 200

Research on the Geography of Agricultural Change: Redundant or Revitalized?

Future research directions for agricultural geography were the subject of debate in Area in the late 1980s. The subsequent application of political economy ideas undoubtedly revived interest in agricultural research. This paper argues that agricultural geography contains greater diversity than the dominant political economy discourse would suggest. It reviews ‘other’ areas of agricultural research on policy, post-productivism, people, culture and animals, presenting future suggestions for research. They should ensure that agricultural research continues revitalized rather than redundant into the next millennium

Brands in international and multi‐platform expansion strategies: economic and management issues

Powerful media branding has historically facilitated successful international expansion on the part of magazine and other content forms including film and TV formats. Multi-platform expansion is now increasingly central to the strategies of media companies and, as this chapter argues, effective use of branding in order to engage audiences effectively and to secure a prominent presence across digital platforms forms a core part of this. Drawing on original research into the experience of UK media companies, this chapter highlights some of the key economic, management and socio-cultural issues raised by the ever-increasing role of brands and branding in the strategies of international and multi-platform expansion that are increasingly common- place across media

Validation of an Immunoassay for anti-thymidine phosphorylase antibodies in patients with MNGIE treated with enzyme replacement therapy

Erythrocyte encapsulated thymidine phosphorylase is recombinant Escherichia coli thymidine phosphorylase encapsulated within human autologous erythrocytes and is under development as an enzyme replacement therapy for the ultra-rare inherited metabolic disorder mitochondrial neurogastrointestinal encephalomyopathy. This study describes the method validation of a two-step bridging electrochemiluminescence immunoassay for the detection of anti-thymidine phosphorylase antibodies in human serum according to current industry practice and regulatory guidelines. The analytical method was assessed for screening cut point, specificity, selectivity, precision, prozone effect, drug tolerance, and stability. Key findings were a correction factor of 129 relative light units for the cut-point determination; a specificity cut point of 93% inhibition; confirmed intra-assay and inter-assay precision; assay sensitivity of 356 ng/mL; no matrix or prozone effects up to 25,900 ng/mL; a drug tolerance of 156 ng/mL; and stability at room temperature for 24 hr and up to five freeze-thaws. Immunogenicity evaluations of serum from three patients who received erythrocyte encapsulated thymidine phosphorylase under a compassionate treatment program showed specific anti-thymidine phosphorylase antibodies in one patient. To conclude, a sensitive, specific, and selective immunoassay has been validated for the measurement of anti-thymidine phosphorylase antibodies; this will be utilized in a phase II pivotal clinical trial of erythrocyte encapsulated thymidine phosphorylase

Photoelectrochemical synthesis of DNA microarrays

Optical addressing of semiconductor electrodes represents a powerful technology that enables the independent and parallel control of a very large number of electrical phenomena at the solid-electrolyte interface. To date, it has been used in a wide range of applications including electrophoretic manipulation, biomolecule sensing, and stimulating networks of neurons. Here, we have adapted this approach for the parallel addressing of redox reactions, and report the construction of a DNA microarray synthesis platform based on semiconductor photoelectrochemistry (PEC). An amorphous silicon photoconductor is activated by an optical projection system to create virtual electrodes capable of electrochemically generating protons; these PEC-generated protons then cleave the acid-labile dimethoxytrityl protecting groups of DNA phosphoramidite synthesis reagents with the requisite spatial selectivity to generate DNA microarrays. Furthermore, a thin-film porous glass dramatically increases the amount of DNA synthesized per chip by over an order of magnitude versus uncoated glass. This platform demonstrates that PEC can be used toward combinatorial bio-polymer and small molecule synthesis.Defense Advanced Research Projects Agency (N66001-05-X6030)National Science Foundation (Grant CCR0122419

Antarctic climate and ice-sheet configuration during the early Pliocene interglacial at 4.23Ma

The geometry of Antarctic ice sheets during warm periods of the geological past is difficult to determine from geological evidence, but is important to know because such reconstructions enable a more complete understanding of how the ice-sheet system responds to changes in climate. Here we investigate how Antarctica evolved under orbital and greenhouse gas conditions representative of an interglacial in the early Pliocene at 4.23Ma, when Southern Hemisphere insolation reached a maximum. Using offline-coupled climate and ice-sheet models, together with a new synthesis of high-latitude palaeoenvironmental proxy data to define a likely climate envelope, we simulate a range of ice-sheet geometries and calculate their likely contribution to sea level. In addition, we use these simulations to investigate the processes by which the West and East Antarctic ice sheets respond to environmental forcings and the timescales over which these behaviours manifest. We conclude that the Antarctic ice sheet contributed 8.6±2.8m to global sea level at this time, under an atmospheric CO2 concentration identical to present (400ppm). Warmer-than-present ocean temperatures led to the collapse of West Antarctica over centuries, whereas higher air temperatures initiated surface melting in parts of East Antarctica that over one to two millennia led to lowering of the ice-sheet surface, flotation of grounded margins in some areas, and retreat of the ice sheet into the Wilkes Subglacial Basin. The results show that regional variations in climate, ice-sheet geometry, and topography produce long-term sea-level contributions that are non-linear with respect to the applied forcings, and which under certain conditions exhibit threshold behaviour associated with behavioural tipping points